LEAD-6: Effect of Liraglutide or Exenatide Added to an Ongoing Treatment on Blood Glucose Control in Subjects With Type 2 Diabetes

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00518882
• Collaborator: (none)
• Enrollment: 467
• Locations: 126
• Arms: 2
• Duration (Months): 20
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This trial is conducted in Europe and the United States of America (USA). The aim of this trial is to compare the effect on glycaemic control of liraglutide or exenatide when added to subject's ongoing OAD (oral anti-diabetic drug) treatment of either metformin, sulphonylurea or a combination of both in subjects with type 2 diabetes. Two trial periods: A 26 week randomised, followed by a 52 week extension (14 + 38 weeks) where all subjects received liraglutide + OAD after previous randomisation to either liraglutide or exenatide, both combined with OAD treatment.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Diabetes Mellitus, Type 2	Drug: liraglutide; Drug: exenatide	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 467 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Liraglutide or Exenatide Added to a Background Treatment of Metformin, Sulphonylurea or a Combination of Both on Glycaemic Control in Subjects With Type 2 Diabetes
• Study Start Date: Aug 1, 2007
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Liraglutide Liraglutide 1.8 mg once daily + subject's own OAD treatment	Drug: liraglutide; 1.8 mg once daily for s.c. (under the skin) injection.
Active Comparator: Exenatide Exenatide 10 mcg twice daily + subject's own OAD treatment	Drug: exenatide; 10 mcg twice daily for s.c. (under the skin) injection.

Outcome Measures

Primary Outcome Measures

1. Change in Glycosylated A1c (HbA1c) at Week 26 [week 0, week 26]

   Percentage point change in glycosylated A1c (HbA1c) from baseline (week 0) to 26 weeks (end of randomisation)

Secondary Outcome Measures

1. Change in Glycosylated A1c (HbA1c), Weeks 26-78 [week 26, week 78]

   Percentage point change in glycosylated A1c (HbA1c) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group)

2. Change in Glycosylated A1c (HbA1c) at Week 78 [week 0, week 78]

   Percentage point change in glycosylated A1c (HbA1c) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group)

3. Percentage of Subjects Achieving Treatment Target of Either HbA1c < 7.0% or =< 6.5% at Week 26 [week 0, week 26]

   Percentage of subjects achieving treatment target of HbA1c less than 7.0% or less than or equal to 6.5% at Week 26 (end of randomisation)

4. Percentage of Subjects Achieving Treatment Target of Either HbA1c < 7.0% or =< 6.5% at Week 78 [week 0, week 78]

   Percentage of subjects achieving treatment target of HbA1c less than 7.0% or less than or equal to 6.5% at Week 78 (end of treatment)

5. Change in Body Weight at Week 26 [week 0, week 26]

   Change in body weight from baseline (week 0) to 26 weeks (end of randomisation)

6. Change in Body Weight, Weeks 26-78 [week 26, week 78]

   Change in body weight from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group)

7. Change in Body Weight at Week 78 [week 0, week 78]

   Change in body weight from baseline (Week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group)

8. Change in Fasting Plasma Glucose at Week 26 [week 0, week 26]

   Change in fasting plasma glucose (FPG) from baseline (week 0) to 26 weeks (end of randomisation)

9. Change in Fasting Plasma Glucose, Weeks 26-78 [week 26, week 78]

   Change in fasting plasma glucose from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group)

10. Change in Fasting Plasma Glucose at Week 78 [week 0, week 78]

    Change in fasting plasma glucose from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group)

11. Change in Mean Prandial Increment of Plasma Glucose After Breakfast at Week 26 [week 0, week 26]

    Change in mean prandial increment of plasma glucose after breakfast from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between glucose values measured before and after breakfast.

12. Change in Mean Prandial Increment of Plasma Glucose After Lunch at Week 26 [week 0, week 26]

    Change in mean prandial increment of plasma glucose after lunch from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch.

13. Change in Mean Prandial Increment of Plasma Glucose After Dinner at Week 26 [week 0, week 26]

    Change in mean prandial increment of plasma glucose after dinner from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner.

14. Change in Mean Prandial Increment of Plasma Glucose After Breakfast, Weeks 26-78 [week 26, week 78]

    Change in mean prandial increment of plasma glucose after breakfast from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast.

15. Change in Mean Prandial Increment of Plasma Glucose After Lunch, Weeks 26-78 [week 26, week 78]

    Change in mean prandial increment of plasma glucose after lunch from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after a lunch.

16. Change in Mean Prandial Increment of Plasma Glucose After Dinner, Weeks 26-78 [week 26, week 78]

    Change in mean prandial increment of plasma glucose after dinner from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner.

17. Change in Mean Prandial Increment of Plasma Glucose After Breakfast at Week 78 [week 0, week 78]

    Change in mean prandial increment of plasma glucose after breakfast from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast.

18. Change in Mean Prandial Increment of Plasma Glucose After Lunch at Week 78 [week 0, week 78]

    Change in mean prandial increment of plasma glucose after lunch from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch.

19. Change in Mean Prandial Increment of Plasma Glucose After Dinner at Week 78 [week 0, week 78]

    Change in mean prandial increment of plasma glucose after dinner from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner.

20. Change in Mean Postprandial Increment of Plasma Glucose After Breakfast at Week 26 [week 0, week 26]

    Change in mean postprandial increment of plasma glucose after breakfast from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast.

21. Change in Mean Postprandial Increment of Plasma Glucose After Lunch at Week 26 [week 0. week 26]

    Change in mean postprandial increment of plasma glucose after lunch from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch.

22. Change in Mean Postprandial Increment of Plasma Glucose After Dinner at Week 26 [week 0, week 26]

    Change in mean postprandial increment of plasma glucose after dinner from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner.

23. Change in Mean Postprandial Increment of Plasma Glucose After Breakfast, Weeks 26-78 [week 26, week 78]

    Change in mean postprandial increment of plasma glucose after breakfast from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast.

24. Change in Mean Postprandial Increment of Plasma Glucose After Lunch, Weeks 26-78 [week 26, week 78]

    Change in mean postprandial increment of plasma glucose after lunch from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch.

25. Change in Mean Postprandial Increment of Plasma Glucose After Dinner, Weeks 26-78 [week 26, week 78]

    Change in mean postprandial increment of plasma glucose after dinner from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner.

26. Change in Mean Postprandial Increment of Plasma Glucose After Breakfast at Week 78 [week 0, week 78]

    Change in mean postprandial increment of plasma glucose after breakfast from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast.

27. Change in Mean Postprandial Increment of Plasma Glucose After Lunch at Week 78 [week 0, week 78]

    Change in mean postprandial increment of plasma glucose after lunch from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch.

28. Change in Mean Postprandial Increment of Plasma Glucose After Dinner at Week 78 [week 0, week 78]

    Change in mean postprandial increment of plasma glucose after dinner from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner.

29. Change in Beta-cell Function at Week 26 [week 0, week 26]

    Change in Beta-cell function from baseline (week 0) to 26 weeks (end of randomisation). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B). Beta-cell function: HOMA-B (%) = 20∙fasting insulin[uU/mL] divided by (FPG mmol/L]-3.5).

30. Change in Beta-cell Function, Weeks 26-78 [week 26, week 78]

    Change in Beta-cell function from Week 26 (end of randomisation) to Week 78 (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B). Beta-cell function: HOMA-B (%) = 20∙fasting insulin[uU/mL] divided by (FPG mmol/L]-3.5).

31. Change in Beta-cell Function at Week 78 [week 0, week 78]

    Change in Beta-cell function from baseline (week 0) to 78 weeks (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B). Beta-cell function: HOMA-B (%) = 20∙fasting insulin[uU/mL] divided by (FPG mmol/L]-3.5).

32. Change in Total Cholesterol at Week 26 [week 0, week 26]

    Change in total cholesterol (TC) from baseline (week 0) to 26 weeks (end of randomisation)

33. Change in Total Cholesterol, Weeks 26-78 [week 26, week 78]

    Change in total cholesterol (TC) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).

34. Change in Total Cholesterol at Week 78 [week 0, week 78]

    Change in total cholesterol (TC) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).

35. Change in Low-density Lipoprotein-cholesterol at Week 26 [week 0, week 26]

    Change in Low-density Lipoprotein-cholesterol (LDL-C) from baseline (week 0) to 26 weeks (end of randomisation)

36. Change in Low-density Lipoprotein-cholesterol, Weeks 26-78 [week 26, week 78]

    Change in low-density lipoprotein-cholesterol (LDL-C) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).

37. Change in Low-density Lipoprotein-cholesterol at Week 78 [week 0, week 78]

    Change in Low-density Lipoprotein-cholesterol (LDL-C) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).

38. Change in Very Low-density Lipoprotein-cholesterol at Week 26 [week 0, week 26]

    Change in very low-density lipoprotein-cholesterol (VLDL-C) from baseline (week 0) to 26 weeks (end of randomisation)

39. Change in Very Low-density Lipoprotein-cholesterol, Weeks 26-78 [week 26, week 78]

    Change in Very Low-density Lipoprotein-cholesterol (VLDL-C) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).

40. Change in Very Low-density Lipoprotein-cholesterol at Week 78 [week 0, week 78]

    Change in Very Low-density Lipoprotein-cholesterol (VLDL-C) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).

41. Change in High-density Lipoprotein-cholesterol at Week 26 [week 0, week 26]

    Change in High-density Lipoprotein-cholesterol (HDL-C) from baseline (week 0) to 26 weeks (end of randomisation)

42. Change in High-density Lipoprotein-cholesterol, Weeks 26-78 [week 26, week 78]

    Change in High-density Lipoprotein-cholesterol (HDL-C) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).

43. Change in High-density Lipoprotein-cholesterol at Week 78 [week 0, week 78]

    Change in High-density Lipoprotein-cholesterol (HDL-C) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).

44. Change in Triglyceride at Week 26 [week 0, week 26]

    Change in triglyceride (TG) from from baseline (week 0) to 26 weeks (end of randomisation)

45. Change in Triglyceride, Weeks 26-78 [week 26, week 78]

    Change in Triglyceride (TG) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).

46. Change in Triglyceride at Week 78 [week 0, week 78]

    Change in triglyceride (TG) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).

47. Change in Free Fatty Acid at Week 26 [week 0, week 26]

    Change in Free Fatty Acid (FFA) from baseline (week 0) to 26 weeks (end of randomisation)

48. Change in Free Fatty Acid, Weeks 26-78 [week 26, week 78]

    Change in Free Fatty Acid (FFA) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).

49. Change in Free Fatty Acid at Week 78 [week 0, week 78]

    Change in Free Fatty Acid (FFA) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).

50. Change in Apolipoprotein B at Week 26 [week 0, week 26]

    Change in apolipoprotein B (ApoB) from baseline (week 0) to 26 weeks (end of randomisation)

51. Change in Apolipoprotein B, Weeks 26-78 [week 26, week 78]

    Change in apolipoprotein B (ApoB) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).

52. Change in Apolipoprotein B at Week 78 [week 0, week 78]

    Change in apolipoprotein B (ApoB) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).

53. Hypoglycaemic Episodes at Week 26 [weeks 0-26]

    Total number of hypoglycaemic episodes occurring after baseline (week 0) and until week 26 (end of randomisation). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose was below 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.

54. Hypoglyceamic Episodes, Weeks 26-78 [weeks 26-78]

    Total number of hypoglycaemic episodes occurring after end of randomisation (week 26) and until week 78 (end of treatment). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose was below 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type 2 diabetes

• Stable treatment with Oral Anti-Diabetic Drugs (metformin, sulphonylurea or a combination of both) for at least 3 months at the discretion of the Investigator

• HbA1C equal to or greater than 7.0% and equal to or lower than 11.0%

• Body Mass Index (BMI) equal to or lower than 45.0 kg/m2

Exclusion Criteria:

• Previous treatment with insulin

• Treatment with any anti-diabetic drug other than metformin and sulphonylurea

• Any previous exposure to exenatide or liraglutide

• Impaired liver or/and renal function

• History of any significant cardiac events

• Known retinopathy or maculopathy requiring acute treatment

• Recurrent major hypoglycaemia or hypoglycaemic unawareness

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Birmingham	Alabama	United States	35242
2	Novo Nordisk Investigational Site	Goodyear	Arizona	United States	85395
3	Novo Nordisk Investigational Site	Artesia	California	United States	90701
4	Novo Nordisk Investigational Site	Encino	California	United States	91436
5	Novo Nordisk Investigational Site	Escondido	California	United States	92025
6	Novo Nordisk Investigational Site	Los Angeles	California	United States	90057
7	Novo Nordisk Investigational Site	Orange	California	United States	92869
8	Novo Nordisk Investigational Site	Sacramento	California	United States	95816
9	Novo Nordisk Investigational Site	San Mateo	California	United States	94401
10	Novo Nordisk Investigational Site	Spring Valley	California	United States	91978
11	Novo Nordisk Investigational Site	Walnut Creek	California	United States	94598
12	Novo Nordisk Investigational Site	Fort Myers	Florida	United States	33907
13	Novo Nordisk Investigational Site	Hollywood	Florida	United States	33023
14	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32205
15	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32216
16	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32259
17	Novo Nordisk Investigational Site	Longwood	Florida	United States	32779
18	Novo Nordisk Investigational Site	Ocala	Florida	United States	34471
19	Novo Nordisk Investigational Site	Pembroke Pines	Florida	United States	33029
20	Novo Nordisk Investigational Site	Plantation	Florida	United States	33324
21	Novo Nordisk Investigational Site	St. Cloud	Florida	United States	34769
22	Novo Nordisk Investigational Site	Atlanta	Georgia	United States	30318
23	Novo Nordisk Investigational Site	Powder Springs	Georgia	United States	30127
24	Novo Nordisk Investigational Site	Roswell	Georgia	United States	30076
25	Novo Nordisk Investigational Site	Idaho Falls	Idaho	United States	83404-7596
26	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60616
27	Novo Nordisk Investigational Site	Peoria	Illinois	United States	61615
28	Novo Nordisk Investigational Site	Evansville	Indiana	United States	47714
29	Novo Nordisk Investigational Site	Des Moines	Iowa	United States	50314-3027
30	Novo Nordisk Investigational Site	New Orleans	Louisiana	United States	70121
31	Novo Nordisk Investigational Site	Minneapolis	Minnesota	United States	55416
32	Novo Nordisk Investigational Site	St. Paul	Minnesota	United States	55108
33	Novo Nordisk Investigational Site	St. Peters	Missouri	United States	63376
34	Novo Nordisk Investigational Site	Flemington	New Jersey	United States	08822
35	Novo Nordisk Investigational Site	South Bound Brook	New Jersey	United States	08880
36	Novo Nordisk Investigational Site	Northport	New York	United States	11768
37	Novo Nordisk Investigational Site	Chapel Hill	North Carolina	United States	27517
38	Novo Nordisk Investigational Site	Canton	Ohio	United States	44718
39	Novo Nordisk Investigational Site	Cincinnati	Ohio	United States	45206
40	Novo Nordisk Investigational Site	Dayton	Ohio	United States	45439
41	Novo Nordisk Investigational Site	Kettering	Ohio	United States	45429
42	Novo Nordisk Investigational Site	Mentor	Ohio	United States	44060
43	Novo Nordisk Investigational Site	Oklahoma City	Oklahoma	United States	73103
44	Novo Nordisk Investigational Site	Altoona	Pennsylvania	United States	16602
45	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19152
46	Novo Nordisk Investigational Site	Pittsburgh	Pennsylvania	United States	15213
47	Novo Nordisk Investigational Site	Sumter	South Carolina	United States	29150
48	Novo Nordisk Investigational Site	Chattanooga	Tennessee	United States	37404
49	Novo Nordisk Investigational Site	Austin	Texas	United States	78731
50	Novo Nordisk Investigational Site	Corpus Christi	Texas	United States	78412
51	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
52	Novo Nordisk Investigational Site	Dallas	Texas	United States	75231
53	Novo Nordisk Investigational Site	Dallas	Texas	United States	75246
54	Novo Nordisk Investigational Site	Houston	Texas	United States	77030
55	Novo Nordisk Investigational Site	Midland	Texas	United States	79707
56	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78229
57	Novo Nordisk Investigational Site	Newport News	Virginia	United States	23606
58	Novo Nordisk Investigational Site	Richmond	Virginia	United States	23294
59	Novo Nordisk Investigational Site	Olympia	Washington	United States	98502
60	Novo Nordisk Investigational Site	Spokane	Washington	United States	99218
61	Novo Nordisk Investigational Site	Milwaukee	Wisconsin	United States	53209
62	Novo Nordisk Investigational Site	Graz		Austria	8036
63	Novo Nordisk Investigational Site	Wien		Austria	1030
64	Novo Nordisk Investigational Site	Wien		Austria	1130
65	Novo Nordisk Investigational Site	Aalborg		Denmark	9000
66	Novo Nordisk Investigational Site	Gentofte		Denmark	2820
67	Novo Nordisk Investigational Site	Hvidovre		Denmark	2650
68	Novo Nordisk Investigational Site	Odense		Denmark	5000
69	Novo Nordisk Investigational Site	Århus C		Denmark	8000
70	Novo Nordisk Investigational Site	Helsinki		Finland	00029
71	Novo Nordisk Investigational Site	Lahti		Finland	15110
72	Novo Nordisk Investigational Site	Oulu		Finland	FI-90100
73	Novo Nordisk Investigational Site	Antibes		France	06600
74	Novo Nordisk Investigational Site	Dommartin Les Toul		France	54201
75	Novo Nordisk Investigational Site	LA ROCHELLE cedex		France	17019
76	Novo Nordisk Investigational Site	Narbonne		France	11108
77	Novo Nordisk Investigational Site	NEVERS cedex		France	58033
78	Novo Nordisk Investigational Site	Bochum		Germany	44791
79	Novo Nordisk Investigational Site	Dreieich-Sprendlingen		Germany	63303
80	Novo Nordisk Investigational Site	Falkensee		Germany	14612
81	Novo Nordisk Investigational Site	Frankfurt		Germany	60388
82	Novo Nordisk Investigational Site	Hamburg		Germany	22607
83	Novo Nordisk Investigational Site	Hannover		Germany	30625
84	Novo Nordisk Investigational Site	Herrenberg		Germany	71083
85	Novo Nordisk Investigational Site	Lampertheim		Germany	68623
86	Novo Nordisk Investigational Site	Ludwigshafen		Germany	67059
87	Novo Nordisk Investigational Site	Marburg		Germany	35039
88	Novo Nordisk Investigational Site	Pohlheim		Germany	35415
89	Novo Nordisk Investigational Site	Rehlingen-Siersburg		Germany	66780
90	Novo Nordisk Investigational Site	Speyer		Germany	67346
91	Novo Nordisk Investigational Site	Tübingen		Germany	72072
92	Novo Nordisk Investigational Site	Dublin 24		Ireland
93	Novo Nordisk Investigational Site	Dublin 9		Ireland
94	Novo Nordisk Investigational Site	Dublin		Ireland	DUBLIN 7
95	Novo Nordisk Investigational Site	Dublin		Ireland	DUBLIN 8
96	Novo Nordisk Investigational Site	Skopje		Macedonia, The Former Yugoslav Republic of	1000
97	Novo Nordisk Investigational Site	Bergen		Norway	5021
98	Novo Nordisk Investigational Site	Bergen		Norway	NO-5012
99	Novo Nordisk Investigational Site	Stavanger		Norway	4011
100	Novo Nordisk Investigational Site	Trondheim		Norway	NO-7030
101	Novo Nordisk Investigational Site	Bydgoszcz		Poland	85-822
102	Novo Nordisk Investigational Site	Gniewkowo		Poland	88-140
103	Novo Nordisk Investigational Site	Krakow		Poland	31-501
104	Novo Nordisk Investigational Site	Lublin		Poland	20-081
105	Novo Nordisk Investigational Site	Poznan		Poland	60-821
106	Novo Nordisk Investigational Site	Tychy		Poland	43-100
107	Novo Nordisk Investigational Site	Warszawa		Poland	01-911
108	Novo Nordisk Investigational Site	Wroclaw		Poland	50-127
109	Novo Nordisk Investigational Site	Zabrze		Poland	41-800
110	Novo Nordisk Investigational Site	Manati		Puerto Rico	00674
111	Novo Nordisk Investigational Site	Alba Iulia	Alba	Romania	510053
112	Novo Nordisk Investigational Site	Resita		Romania	320076
113	Novo Nordisk Investigational Site	Suceava		Romania	720237
114	Novo Nordisk Investigational Site	Koper		Slovenia	SI-6000
115	Novo Nordisk Investigational Site	Ljubljana		Slovenia	1525
116	Novo Nordisk Investigational Site	Novo mesto		Slovenia	8000
117	Novo Nordisk Investigational Site	Hospitalet de Llobregat		Spain	08907
118	Novo Nordisk Investigational Site	Oviedo		Spain	33006
119	Novo Nordisk Investigational Site	Palma de Mallorca		Spain	07010
120	Novo Nordisk Investigational Site	Puerto del Rosario		Spain	35600
121	Novo Nordisk Investigational Site	Stockholm		Sweden	141 86
122	Novo Nordisk Investigational Site	Stockholm		Sweden	171 76
123	Novo Nordisk Investigational Site	Basel		Switzerland	4031
124	Novo Nordisk Investigational Site	Bern		Switzerland	3010
125	Novo Nordisk Investigational Site	Genève 14		Switzerland	1211
126	Novo Nordisk Investigational Site	Lugano		Switzerland	6900

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical Trials at Novo Nordisk

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT00518882
• Other Study ID Numbers: NN2211-1797; 2006-006092-21
• First Posted: Aug 21, 2007
• Last Update Posted: Mar 8, 2017
• Last Verified: Jan 1, 2017

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Liraglutide; Exenatide

Study Results

Participant Flow

Recruitment Details	A total of 133 centres in 15 countries: Austria (4), Denmark (6), Finland (5), France (5), Germany (14), Ireland (4), Macedonia (1), Norway (4), Poland (9), Romania (3), Slovenia (3), Spain (4), Sweden (2), Switzerland (4) and United States (65).
Pre-assignment Detail	Eligible subjects were subjects with type 2 diabetes being treated with oral anti-diabetic (OAD) therapy(ies) for at least 3 months prior to the study. Three subjects were exposed to study drug prior to randomisation, and thus only included in safety analysis set.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Period Title: Double-Blind, Week 0-26
STARTED	235	232
Randomised	233	231
COMPLETED	202	187
NOT COMPLETED	33	45
Period Title: Double-Blind, Week 0-26
STARTED	202	187
COMPLETED	161	138
NOT COMPLETED	41	49

Baseline Characteristics

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide	Total
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Total of all reporting groups
Overall Participants	233	231	464
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.3 (9.8)	57.1 (10.8)	56.7 (10.3)
Sex: Female, Male (Count of Participants)
Female	119 51.1%	104 45%	223 48.1%
Male	114 48.9%	127 55%	241 51.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	32 13.7%	25 10.8%	57 12.3%
Not Hispanic or Latino	201 86.3%	206 89.2%	407 87.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 0.4%	1 0.2%
Asian	0 0%	4 1.7%	4 0.9%
Native Hawaiian or Other Pacific Islander	1 0.4%	1 0.4%	2 0.4%
Black or African American	13 5.6%	12 5.2%	25 5.4%
White	216 92.7%	210 90.9%	426 91.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	3 1.3%	3 1.3%	6 1.3%
Previous OAD treatment (participants) [Number]
Metformin/Sulphonylurea Combination	145 62.2%	147 63.6%	292 62.9%
Sulphonylurea	24 10.3%	21 9.1%	45 9.7%
Metformin	64 27.5%	63 27.3%	127 27.4%
BMI (kg/m2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m2]	32.9 (5.5)	32.9 (5.7)	32.9 (5.6)
Duration of diabetes (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.5 (6.2)	7.9 (5.9)	8.2 (6.0)
HbA1c (percentage of total haemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of total haemoglobin]	8.4 (1.0)	8.2 (1.0)	8.3 (1.0)
Height (m) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [m]	1.68 (0.10)	1.68 (0.10)	1.68 (0.10)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	93.1 (20.1)	93.0 (19.5)	93.1 (19.8)

Outcome Measures

1. Primary Outcome

Title	Change in Glycosylated A1c (HbA1c) at Week 26
Description	Percentage point change in glycosylated A1c (HbA1c) from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame	week 0, week 26

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	227	226
Least Squares Mean (Standard Error) [percentage point of total HbA1c]	-1.12 (0.08)	-0.79 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide, Exenatide -> Liraglutide -> Liraglutide
	Comments	ANCOVA with treatment, country and previous OAD treatment as fixed effects and baseline HbA1c as covariate. 2 hypotheses were tested: H01: µliraglutide ≥ µexenatide + Δ, HA1: µliraglutide < µexenatide + Δ; Δ=0.4%. If non-inferiority was concluded, a test for superiority was established by a 1-sided test of the hypothesis H02: µliraglutide ≥ µexenatide against HA2: µliraglutide < µexenatide. Superiority was concluded if the upper limit of the 2-sided 95% CI for the difference was below 0%.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority concluded if upper confidence interval of test is below 0.4%
Statistical Test of Hypothesis	p-Value	<.0001
	Comments	No multiplicity concerns
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	-0.33
	Confidence Interval	() 95%; -0.47 to -0.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in Glycosylated A1c (HbA1c), Weeks 26-78
Description	Percentage point change in glycosylated A1c (HbA1c) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group)
Time Frame	week 26, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	198	183
Mean (Standard Deviation) [percentage point of total HbA1c]	0.25 (0.803)	-0.00 (0.924)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t-test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.25
	Confidence Interval	() 95%; 0.139 to 0.364
	Parameter Dispersion	Type: Standard Deviation; Value: 0.803
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9872
	Comments
	Method	Paired t-test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.00
	Confidence Interval	() 95%; -1.36 to 0.134
	Parameter Dispersion	Type: Standard Deviation; Value: 0.924
	Estimation Comments

3. Secondary Outcome

Title	Change in Glycosylated A1c (HbA1c) at Week 78
Description	Percentage point change in glycosylated A1c (HbA1c) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group)
Time Frame	week 0, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	198	183
Mean (Standard Deviation) [percentage point of total HbA1c]	-0.98 (1.119)	-0.85 (1.105)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% confidence intervals for the difference between Weeks 0 and 78 were constructed. H0 was µ78 - µ0 = 0 against HA: µ78 - µ0 ≠ 0. A difference between the two means (Weeks 0 and 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t-test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.98
	Confidence Interval	() 95%; -1.137 to -0.823
	Parameter Dispersion	Type: Standard Deviation; Value: 1.119
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the exenatide→liraglutide group and 95% confidence intervals for the difference between Weeks 0 and 78 were constructed. H0 was µ78 - µ0 = 0 against HA: µ78 - µ0 ≠ 0. A difference between the two means (Weeks 0 and 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t-test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.85
	Confidence Interval	() 95%; -1.010 to -0.687
	Parameter Dispersion	Type: Standard Deviation; Value: 1.105
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Subjects Achieving Treatment Target of Either HbA1c < 7.0% or =< 6.5% at Week 26
Description	Percentage of subjects achieving treatment target of HbA1c less than 7.0% or less than or equal to 6.5% at Week 26 (end of randomisation)
Time Frame	week 0, week 26

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	233	231
Treatment target HbA1c < 7%	53	42
Treatment target HbA1c =< 6.5%	34	20

5. Secondary Outcome

Title	Percentage of Subjects Achieving Treatment Target of Either HbA1c < 7.0% or =< 6.5% at Week 78
Description	Percentage of subjects achieving treatment target of HbA1c less than 7.0% or less than or equal to 6.5% at Week 78 (end of treatment)
Time Frame	week 0, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	200	186
Treatment target HbA1c < 7%	47	48
Treatment target HbA1c =< 6.5%	31	35

6. Secondary Outcome

Title	Change in Body Weight at Week 26
Description	Change in body weight from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame	week 0, week 26

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	231	229
Least Squares Mean (Standard Error) [kg]	-3.24 (0.33)	-2.87 (0.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide, Exenatide -> Liraglutide -> Liraglutide
	Comments	ANCOVA model included treatment, country and previous treatment as fixed effects and baseline body weight as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the body weight in the liraglutide arm and exenatide arm, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2235
	Comments	There were no multiplicity concerns.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	-0.38
	Confidence Interval	() 95%; -0.99 to 0.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change in Body Weight, Weeks 26-78
Description	Change in body weight from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group)
Time Frame	week 26, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	199	184
Mean (Standard Deviation) [kg]	-0.4 (3.24)	-0.7 (3.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26=0 against HA: µ78 - µ26 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0793
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.4
	Confidence Interval	() 95%; -0.86 to 0.05
	Parameter Dispersion	Type: Standard Deviation; Value: 3.24
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0075
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.7
	Confidence Interval	() 95%; -1.26 to -0.20
	Parameter Dispersion	Type: Standard Deviation; Value: 3.67
	Estimation Comments

8. Secondary Outcome

Title	Change in Body Weight at Week 78
Description	Change in body weight from baseline (Week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group)
Time Frame	week 0, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	199	184
Mean (Standard Deviation) [kg]	-3.3 (4.63)	-3.2 (4.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-3.3
	Confidence Interval	() 95%; -3.90 to -2.61
	Parameter Dispersion	Type: Standard Deviation; Value: 4.63
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-3.2
	Confidence Interval	() 95%; -3.85 to -2.55
	Parameter Dispersion	Type: Standard Deviation; Value: 4.44
	Estimation Comments

9. Secondary Outcome

Title	Change in Fasting Plasma Glucose at Week 26
Description	Change in fasting plasma glucose (FPG) from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame	week 0, week 26

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	225	219
Least Squares Mean (Standard Error) [mmol/L]	-1.61 (0.20)	-0.60 (0.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide, Exenatide -> Liraglutide -> Liraglutide
	Comments	ANCOVA model included treatment, country and previous treatment as fixed effects and baseline fasting plasma glucose as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the fasting plasma glucose in the liraglutide and exenatide arm, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	There were no multiplicity concerns.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	-1.01
	Confidence Interval	() 95%; -1.37 to -0.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change in Fasting Plasma Glucose, Weeks 26-78
Description	Change in fasting plasma glucose from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group)
Time Frame	week 26, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	197	182
Mean (Standard Deviation) [mmol/L]	0.7 (1.84)	-0.1 (2.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 26 and 78 were constructed. H0 was µ78- µ26=0 against HA: µ78 - µ26 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.7
	Confidence Interval	() 95%; 0.48 to 1.00
	Parameter Dispersion	Type: Standard Deviation; Value: 1.84
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4864
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.1
	Confidence Interval	() 95%; -0.48 to 0.23
	Parameter Dispersion	Type: Standard Deviation; Value: 2.42
	Estimation Comments

11. Secondary Outcome

Title	Change in Fasting Plasma Glucose at Week 78
Description	Change in fasting plasma glucose from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group)
Time Frame	week 0, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	197	182
Mean (Standard Deviation) [mmol/L]	-1.3 (2.50)	-0.8 (2.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78 - µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-1.3
	Confidence Interval	() 95%; -1.62 to -0.92
	Parameter Dispersion	Type: Standard Deviation; Value: 2.50
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78 - µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.8
	Confidence Interval	() 95%; -1.23 to -0.42
	Parameter Dispersion	Type: Standard Deviation; Value: 2.76
	Estimation Comments

12. Secondary Outcome

Title	Change in Mean Prandial Increment of Plasma Glucose After Breakfast at Week 26
Description	Change in mean prandial increment of plasma glucose after breakfast from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between glucose values measured before and after breakfast.
Time Frame	week 0, week 26

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	207	196
Least Squares Mean (Standard Error) [mmol/L]	-0.83 (0.28)	-2.16 (0.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide, Exenatide -> Liraglutide -> Liraglutide
	Comments	ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments	There were no multiplicity concerns.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	1.33
	Confidence Interval	() 95%; 0.80 to 1.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Change in Mean Prandial Increment of Plasma Glucose After Lunch at Week 26
Description	Change in mean prandial increment of plasma glucose after lunch from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch.
Time Frame	week 0, week 26

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	207	196
Least Squares Mean (Standard Error) [mmol/L]	0.06 (0.28)	0.06 (0.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide, Exenatide -> Liraglutide -> Liraglutide
	Comments	ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9849
	Comments	There were no multiplicity concerns.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	0.01
	Confidence Interval	() 95%; -0.52 to 0.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Change in Mean Prandial Increment of Plasma Glucose After Dinner at Week 26
Description	Change in mean prandial increment of plasma glucose after dinner from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner.
Time Frame	week 0, week 26

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	204	196
Least Squares Mean (Standard Error) [mmol/L]	-1.10 (0.31)	-2.11 (0.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide, Exenatide -> Liraglutide -> Liraglutide
	Comments	ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments	There were no multiplicity concerns.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean
	Estimated Value	1.01
	Confidence Interval	() 95%; 0.44 to 1.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Change in Mean Prandial Increment of Plasma Glucose After Breakfast, Weeks 26-78
Description	Change in mean prandial increment of plasma glucose after breakfast from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast.
Time Frame	week 26, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	191	173
Mean (Standard Deviation) [mmol/L]	-0.22 (2.866)	1.15 (3.253)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2972
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.22
	Confidence Interval	() 95%; -0.626 to 0.192
	Parameter Dispersion	Type: Standard Deviation; Value: 2.866
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	1.15
	Confidence Interval	() 95%; 0.660 to 1.637
	Parameter Dispersion	Type: Standard Deviation; Value: 3.253
	Estimation Comments

16. Secondary Outcome

Title	Change in Mean Prandial Increment of Plasma Glucose After Lunch, Weeks 26-78
Description	Change in mean prandial increment of plasma glucose after lunch from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after a lunch.
Time Frame	week 26, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	191	173
Mean (Standard Deviation) [mmol/L]	0.05 (3.307)	-0.09 (3.419)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8396
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.05
	Confidence Interval	() 95%; -0.424 to 0.521
	Parameter Dispersion	Type: Standard Deviation; Value: 3.307
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7278
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.09
	Confidence Interval	() 95%; -0.604 to 0.423
	Parameter Dispersion	Type: Standard Deviation; Value: 3.419
	Estimation Comments

17. Secondary Outcome

Title	Change in Mean Prandial Increment of Plasma Glucose After Dinner, Weeks 26-78
Description	Change in mean prandial increment of plasma glucose after dinner from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner.
Time Frame	week 26, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	190	172
Mean (Standard Deviation) [mmol/L]	0.22 (3.053)	1.07 (3.775)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3271
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.22
	Confidence Interval	() 95%; -0.219 to 0.654
	Parameter Dispersion	Type: Standard Deviation; Value: 3.053
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	1.07
	Confidence Interval	() 95%; 0.497 to 1.634
	Parameter Dispersion	Type: Standard Deviation; Value: 3.775
	Estimation Comments

18. Secondary Outcome

Title	Change in Mean Prandial Increment of Plasma Glucose After Breakfast at Week 78
Description	Change in mean prandial increment of plasma glucose after breakfast from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast.
Time Frame	week 0, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	192	167
Mean (Standard Deviation) [mmol/L]	-1.08 (3.662)	-0.99 (3.467)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-1.08
	Confidence Interval	() 95%; -1.605 to -0.562
	Parameter Dispersion	Type: Standard Deviation; Value: 3.662
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.99
	Confidence Interval	() 95%; -1.517 to -0.458
	Parameter Dispersion	Type: Standard Deviation; Value: 3.467
	Estimation Comments

19. Secondary Outcome

Title	Change in Mean Prandial Increment of Plasma Glucose After Lunch at Week 78
Description	Change in mean prandial increment of plasma glucose after lunch from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch.
Time Frame	week 0, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	192	168
Mean (Standard Deviation) [mmol/L]	0.26 (4.158)	-0.37 (3.838)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3859
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.26
	Confidence Interval	() 95%; -0.331 to 0.853
	Parameter Dispersion	Type: Standard Deviation; Value: 4.158
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2119
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.37
	Confidence Interval	() 95%; -0.956 to 0.214
	Parameter Dispersion	Type: Standard Deviation; Value: 3.838
	Estimation Comments

20. Secondary Outcome

Title	Change in Mean Prandial Increment of Plasma Glucose After Dinner at Week 78
Description	Change in mean prandial increment of plasma glucose after dinner from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner.
Time Frame	week 0, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	190	166
Mean (Standard Deviation) [mmol/L]	-0.35 (3.975)	-0.95 (3.230)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2290
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.35
	Confidence Interval	() 95%; -0.917 to 0.2211
	Parameter Dispersion	Type: Standard Deviation; Value: 3.975
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.95
	Confidence Interval	() 95%; -1.449 to -0.459
	Parameter Dispersion	Type: Standard Deviation; Value: 3.230
	Estimation Comments

21. Secondary Outcome

Title	Change in Mean Postprandial Increment of Plasma Glucose After Breakfast at Week 26
Description	Change in mean postprandial increment of plasma glucose after breakfast from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast.
Time Frame	week 0, week 26

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	207	197
Least Squares Mean (Standard Error) [mmol/L]	-3.20 (0.31)	-3.93 (0.30)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide, Exenatide -> Liraglutide -> Liraglutide
	Comments	ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0124
	Comments	There were no multiplicity concerns.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	0.73
	Confidence Interval	() 95%; 0.16 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

22. Secondary Outcome

Title	Change in Mean Postprandial Increment of Plasma Glucose After Lunch at Week 26
Description	Change in mean postprandial increment of plasma glucose after lunch from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch.
Time Frame	week 0. week 26

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	208	196
Least Squares Mean (Standard Error) [mmol/L]	-2.74 (0.28)	-2.35 (0.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide, Exenatide -> Liraglutide -> Liraglutide
	Comments	ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1430
	Comments	There were no multiplicity concerns.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	-0.39
	Confidence Interval	() 95%; -0.91 to 0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. Secondary Outcome

Title	Change in Mean Postprandial Increment of Plasma Glucose After Dinner at Week 26
Description	Change in mean postprandial increment of plasma glucose after dinner from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner.
Time Frame	week 0, week 26

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	206	197
Least Squares Mean (Standard Error) [mmol/L]	-3.05 (0.28)	-3.59 (0.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide, Exenatide -> Liraglutide -> Liraglutide
	Comments	ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0380
	Comments	There were no multiplicity concerns.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	0.54
	Confidence Interval	() 95%; 0.03 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Secondary Outcome

Title	Change in Mean Postprandial Increment of Plasma Glucose After Breakfast, Weeks 26-78
Description	Change in mean postprandial increment of plasma glucose after breakfast from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast.
Time Frame	week 26, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	191	173
Mean (Standard Deviation) [mmol/L]	0.06 (2.827)	0.72 (3.270)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7700
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.06
	Confidence Interval	() 95%; -0.344 to 0.463
	Parameter Dispersion	Type: Standard Deviation; Value: 2.827
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0042
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.72
	Confidence Interval	() 95%; 0.230 to 1.212
	Parameter Dispersion	Type: Standard Deviation; Value: 3.270
	Estimation Comments

25. Secondary Outcome

Title	Change in Mean Postprandial Increment of Plasma Glucose After Lunch, Weeks 26-78
Description	Change in mean postprandial increment of plasma glucose after lunch from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch.
Time Frame	week 26, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	191	173
Mean (Standard Deviation) [mmol/L]	0.67 (3.041)	-0.09 (2.989)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0026
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.67
	Confidence Interval	() 95%; 0.238 to 1.106
	Parameter Dispersion	Type: Standard Deviation; Value: 3.041
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6845
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.09
	Confidence Interval	() 95%; -0.541 to 0.356
	Parameter Dispersion	Type: Standard Deviation; Value: 2.989
	Estimation Comments

26. Secondary Outcome

Title	Change in Mean Postprandial Increment of Plasma Glucose After Dinner, Weeks 26-78
Description	Change in mean postprandial increment of plasma glucose after dinner from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner.
Time Frame	week 26, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	191	172
Mean (Standard Deviation) [mmol/L]	0.32 (2.705)	0.58 (3.114)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1041
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.32
	Confidence Interval	() 95%; -0.066 to 0.706
	Parameter Dispersion	Type: Standard Deviation; Value: 2.705
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0151
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.58
	Confidence Interval	() 95%; 0.114 to 1.052
	Parameter Dispersion	Type: Standard Deviation; Value: 3.114
	Estimation Comments

27. Secondary Outcome

Title	Change in Mean Postprandial Increment of Plasma Glucose After Breakfast at Week 78
Description	Change in mean postprandial increment of plasma glucose after breakfast from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast.
Time Frame	week 0, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	192	168
Mean (Standard Deviation) [mmol/L]	-3.31 (3.857)	-3.13 (3.560)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-3.31
	Confidence Interval	() 95%; -3.861 to -2.763
	Parameter Dispersion	Type: Standard Deviation; Value: 3.857
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-3.13
	Confidence Interval	() 95%; -3.673 to -2.589
	Parameter Dispersion	Type: Standard Deviation; Value: 3.560
	Estimation Comments

28. Secondary Outcome

Title	Change in Mean Postprandial Increment of Plasma Glucose After Lunch at Week 78
Description	Change in mean postprandial increment of plasma glucose after lunch from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch.
Time Frame	week 0, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	192	168
Mean (Standard Deviation) [mmol/L]	-1.93 (3.703)	-2.17 (3.654)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-1.93
	Confidence Interval	() 95%; -2.457 to -1.403
	Parameter Dispersion	Type: Standard Deviation; Value: 3.703
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-2.17
	Confidence Interval	() 95%; -2.731 to -1.618
	Parameter Dispersion	Type: Standard Deviation; Value: 3.654
	Estimation Comments

29. Secondary Outcome

Title	Change in Mean Postprandial Increment of Plasma Glucose After Dinner at Week 78
Description	Change in mean postprandial increment of plasma glucose after dinner from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner.
Time Frame	week 0, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	191	167
Mean (Standard Deviation) [mmol/L]	-2.21 (3.752)	-2.55 (3.625)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-2.21
	Confidence Interval	() 95%; -2.747 to -1.676
	Parameter Dispersion	Type: Standard Deviation; Value: 3.752
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-2.55
	Confidence Interval	() 95%; -3.104 to -1.997
	Parameter Dispersion	Type: Standard Deviation; Value: 3.625
	Estimation Comments

30. Secondary Outcome

Title	Change in Beta-cell Function at Week 26
Description	Change in Beta-cell function from baseline (week 0) to 26 weeks (end of randomisation). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B). Beta-cell function: HOMA-B (%) = 20∙fasting insulin[uU/mL] divided by (FPG mmol/L]-3.5).
Time Frame	week 0, week 26

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	214	214
Least Squares Mean (Standard Error) [percentage point (%point)]	32.12 (6.75)	2.74 (6.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide, Exenatide -> Liraglutide -> Liraglutide
	Comments	ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments	There were no multiplicity concerns.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	29.37
	Confidence Interval	() 95%; 16.81 to 41.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

31. Secondary Outcome

Title	Change in Beta-cell Function, Weeks 26-78
Description	Change in Beta-cell function from Week 26 (end of randomisation) to Week 78 (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B). Beta-cell function: HOMA-B (%) = 20∙fasting insulin[uU/mL] divided by (FPG mmol/L]-3.5).
Time Frame	week 26, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	198	179
Mean (Standard Deviation) [percentage point (%point)]	-18.18 (62.811)	2.29 (52.997)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-18.18
	Confidence Interval	() 95%; -26.988 to -9.382
	Parameter Dispersion	Type: Standard Deviation; Value: 62.811
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5304
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	2.49
	Confidence Interval	() 95%; -5.327 to 10.307
	Parameter Dispersion	Type: Standard Deviation; Value: 52.997
	Estimation Comments

32. Secondary Outcome

Title	Change in Beta-cell Function at Week 78
Description	Change in Beta-cell function from baseline (week 0) to 78 weeks (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B). Beta-cell function: HOMA-B (%) = 20∙fasting insulin[uU/mL] divided by (FPG mmol/L]-3.5).
Time Frame	week 0, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	189	176
Mean (Standard Deviation) [percentage point (%point)]	24.86 (59.326)	11.13 (87.145)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	24.86
	Confidence Interval	() 95%; 16.348 to 33.374
	Parameter Dispersion	Type: Standard Deviation; Value: 59.326
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0920
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	11.13
	Confidence Interval	() 95%; -1.835 to 24.093
	Parameter Dispersion	Type: Standard Deviation; Value: 87.145
	Estimation Comments

33. Secondary Outcome

Title	Change in Total Cholesterol at Week 26
Description	Change in total cholesterol (TC) from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame	week 0, week 26

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	226	220
Least Squares Mean (Standard Error) [mmol/L]	-0.20 (0.07)	-0.09 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide, Exenatide -> Liraglutide -> Liraglutide
	Comments	ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0946
	Comments	There were no multiplicity concerns.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	-0.11
	Confidence Interval	() 95%; -0.23 to 0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

34. Secondary Outcome

Title	Change in Total Cholesterol, Weeks 26-78
Description	Change in total cholesterol (TC) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame	week 26, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the trial products.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	199	184
Mean (Standard Deviation) [mmol/L]	0.11 (0.774)	0.12 (0.804)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0513
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.11
	Confidence Interval	() 95%; -0.001 to 0.216
	Parameter Dispersion	Type: Standard Deviation; Value: 0.774
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0513
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.12
	Confidence Interval	() 95%; -0.001 to 0.233
	Parameter Dispersion	Type: Standard Deviation; Value: 0.804
	Estimation Comments

35. Secondary Outcome

Title	Change in Total Cholesterol at Week 78
Description	Change in total cholesterol (TC) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame	week 0, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	198	183
Mean (Standard Deviation) [mmol/L]	-0.07 (0.859)	0.09 (0.890)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2764
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.07
	Confidence Interval	() 95%; -0.187 to 0.054
	Parameter Dispersion	Type: Standard Deviation; Value: 0.859
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1911
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.09
	Confidence Interval	() 95%; -0.043 to 0.216
	Parameter Dispersion	Type: Standard Deviation; Value: 0.890
	Estimation Comments

36. Secondary Outcome

Title	Change in Low-density Lipoprotein-cholesterol at Week 26
Description	Change in Low-density Lipoprotein-cholesterol (LDL-C) from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame	week 0, week 26

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	219	215
Least Squares Mean (Standard Error) [mmol/L]	-0.44 (0.06)	-0.40 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide, Exenatide -> Liraglutide -> Liraglutide
	Comments	ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4412
	Comments	There were no multiplicity concerns.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	-0.04
	Confidence Interval	() 95%; -0.15 to 0.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

37. Secondary Outcome

Title	Change in Low-density Lipoprotein-cholesterol, Weeks 26-78
Description	Change in low-density lipoprotein-cholesterol (LDL-C) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame	week 26, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	199	180
Mean (Standard Deviation) [mmol/L]	0.03 (0.606)	0.08 (0.720)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4746
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.03
	Confidence Interval	() 95%; -0.054 to 0.115
	Parameter Dispersion	Type: Standard Deviation; Value: 0.606
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1281
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.08
	Confidence Interval	() 95%; -0.024 to 0.188
	Parameter Dispersion	Type: Standard Deviation; Value: 0.720
	Estimation Comments

38. Secondary Outcome

Title	Change in Low-density Lipoprotein-cholesterol at Week 78
Description	Change in Low-density Lipoprotein-cholesterol (LDL-C) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame	week 0, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	183	176
Mean (Standard Deviation) [mmol/L]	-0.30 (0.604)	-0.21 (0.647)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.30
	Confidence Interval	() 95%; -0.390 to -0.214
	Parameter Dispersion	Type: Standard Deviation; Value: 0.604
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.21
	Confidence Interval	() 95%; -0.303 to -0.110
	Parameter Dispersion	Type: Standard Deviation; Value: 0.647
	Estimation Comments

39. Secondary Outcome

Title	Change in Very Low-density Lipoprotein-cholesterol at Week 26
Description	Change in very low-density lipoprotein-cholesterol (VLDL-C) from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame	week 0, week 26

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	216	212
Least Squares Mean (Standard Error) [mmol/L]	0.20 (0.04)	0.27 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide, Exenatide -> Liraglutide -> Liraglutide
	Comments	ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0277
	Comments	There were no multiplicity concerns.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	-0.07
	Confidence Interval	() 95%; -0.13 to -0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

40. Secondary Outcome

Title	Change in Very Low-density Lipoprotein-cholesterol, Weeks 26-78
Description	Change in Very Low-density Lipoprotein-cholesterol (VLDL-C) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame	week 26, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	199	180
Mean (Standard Deviation) [mmol/L]	0.06 (0.290)	0.03 (0.307)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0030
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.06
	Confidence Interval	() 95%; 0.021 to 0.102
	Parameter Dispersion	Type: Standard Deviation; Value: 0.290
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1452
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.03
	Confidence Interval	() 95%; -0.012 to 0.079
	Parameter Dispersion	Type: Standard Deviation; Value: 0.307
	Estimation Comments

41. Secondary Outcome

Title	Change in Very Low-density Lipoprotein-cholesterol at Week 78
Description	Change in Very Low-density Lipoprotein-cholesterol (VLDL-C) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame	week 0, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	173	168
Mean (Standard Deviation) [mmol/L]	0.27 (0.306)	0.31 (0.346)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.27
	Confidence Interval	() 95%; 0.223 to 0.315
	Parameter Dispersion	Type: Standard Deviation; Value: 0.306
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.31
	Confidence Interval	() 95%; 0.259 to 0.364
	Parameter Dispersion	Type: Standard Deviation; Value: 0.346
	Estimation Comments

42. Secondary Outcome

Title	Change in High-density Lipoprotein-cholesterol at Week 26
Description	Change in High-density Lipoprotein-cholesterol (HDL-C) from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame	week 0, week 26

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	226	220
Least Squares Mean (Standard Error) [mmol/L]	-0.04 (0.02)	-0.05 (0.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide, Exenatide -> Liraglutide -> Liraglutide
	Comments	ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5105
	Comments	There were no multiplicity concerns.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	0.01
	Confidence Interval	() 95%; -0.02 to 0.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

43. Secondary Outcome

Title	Change in High-density Lipoprotein-cholesterol, Weeks 26-78
Description	Change in High-density Lipoprotein-cholesterol (HDL-C) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame	week 26, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	119	180
Mean (Standard Deviation) [mmol/L]	-0.01 (0.150)	0.00 (0.141)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2220
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.01
	Confidence Interval	() 95%; -0.034 to 0.008
	Parameter Dispersion	Type: Standard Deviation; Value: 0.150
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7923
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.00
	Confidence Interval	() 95%; -0.018 to 0.024
	Parameter Dispersion	Type: Standard Deviation; Value: 0.141
	Estimation Comments

44. Secondary Outcome

Title	Change in High-density Lipoprotein-cholesterol at Week 78
Description	Change in High-density Lipoprotein-cholesterol (HDL-C) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame	week 0, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	183	176
Mean (Standard Deviation) [mmol/L]	-0.03 (0.159)	-0.02 (0.165)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0254
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.03
	Confidence Interval	() 95%; -0.050 to -0.003
	Parameter Dispersion	Type: Standard Deviation; Value: 0.159
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2244
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.02
	Confidence Interval	() 95%; -0.040 to 0.009
	Parameter Dispersion	Type: Standard Deviation; Value: 0.165
	Estimation Comments

45. Secondary Outcome

Title	Change in Triglyceride at Week 26
Description	Change in triglyceride (TG) from from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame	week 0, week 26

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	225	220
Least Squares Mean (Standard Error) [mmol/L]	-0.41 (0.10)	-0.23 (0.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide, Exenatide -> Liraglutide -> Liraglutide
	Comments	ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0485
	Comments	There were no multiplicity concerns.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	-0.18
	Confidence Interval	() 95%; -0.37 to -0.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

46. Secondary Outcome

Title	Change in Triglyceride, Weeks 26-78
Description	Change in Triglyceride (TG) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame	week 26, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	198	184
Mean (Standard Deviation) [mmol/L]	0.1 (0.82)	-0.0 (0.96)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1161
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.1
	Confidence Interval	() 95%; -0.02 to 0.21
	Parameter Dispersion	Type: Standard Deviation; Value: 0.82
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7888
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.0
	Confidence Interval	() 95%; -0.16 to 0.12
	Parameter Dispersion	Type: Standard Deviation; Value: 0.96
	Estimation Comments

47. Secondary Outcome

Title	Change in Triglyceride at Week 78
Description	Change in triglyceride (TG) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame	week 0, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	198	183
Mean (Standard Deviation) [mmol/L]	-0.3 (1.07)	-0.1 (1.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.3
	Confidence Interval	() 95%; -0.43 to -0.13
	Parameter Dispersion	Type: Standard Deviation; Value: 1.07
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2078
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.1
	Confidence Interval	() 95%; -0.35 to 0.08
	Parameter Dispersion	Type: Standard Deviation; Value: 1.47
	Estimation Comments

48. Secondary Outcome

Title	Change in Free Fatty Acid at Week 26
Description	Change in Free Fatty Acid (FFA) from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame	week 0, week 26

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	220	222
Least Squares Mean (Standard Error) [mmol/L]	-0.17 (0.02)	-0.10 (0.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide, Exenatide -> Liraglutide -> Liraglutide
	Comments	ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0014
	Comments	There were no multiplicity concerns.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	-0.07
	Confidence Interval	() 95%; -0.11 to -0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

49. Secondary Outcome

Title	Change in Free Fatty Acid, Weeks 26-78
Description	Change in Free Fatty Acid (FFA) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame	week 26, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	199	182
Mean (Standard Deviation) [mmol/L]	0.06 (0.269)	0.01 (0.272)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0018
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.06
	Confidence Interval	() 95%; 0.023 to 0.098
	Parameter Dispersion	Type: Standard Deviation; Value: 0.269
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5499
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	0.01
	Confidence Interval	() 95%; -0.028 to 0.052
	Parameter Dispersion	Type: Standard Deviation; Value: 0.272
	Estimation Comments

50. Secondary Outcome

Title	Change in Free Fatty Acid at Week 78
Description	Change in Free Fatty Acid (FFA) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame	week 0, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	195	182
Mean (Standard Deviation) [mmol/L]	-0.10 (0.273)	-0.07 (0.302)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.10
	Confidence Interval	() 95%; -0.140 to -0.062
	Parameter Dispersion	Type: Standard Deviation; Value: 0.273
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.07
	Confidence Interval	() 95%; -0.118 to -0.030
	Parameter Dispersion	Type: Standard Deviation; Value: 0.302
	Estimation Comments

51. Secondary Outcome

Title	Change in Apolipoprotein B at Week 26
Description	Change in apolipoprotein B (ApoB) from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame	week 0, week 26

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	226	222
Least Squares Mean (Standard Error) [g/L]	-0.06 (0.02)	-0.03 (0.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide, Exenatide -> Liraglutide -> Liraglutide
	Comments	ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1119
	Comments	There were no multiplicity concerns.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference, LS Mean
	Estimated Value	-0.02
	Confidence Interval	() 95%; -0.05 to 0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

52. Secondary Outcome

Title	Change in Apolipoprotein B, Weeks 26-78
Description	Change in apolipoprotein B (ApoB) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame	week 26, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	199	184
Mean (Standard Deviation) [g/L]	-0.02 (0.168)	-0.03 (0.189)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1342
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.02
	Confidence Interval	() 95%; -0.041 to 0.006
	Parameter Dispersion	Type: Standard Deviation; Value: 0.168
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 - µ26 = 0 against HA: µ78 - µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0344
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.03
	Confidence Interval	() 95%; -0.057 to -0.002
	Parameter Dispersion	Type: Standard Deviation; Value: 0.189
	Estimation Comments

53. Secondary Outcome

Title	Change in Apolipoprotein B at Week 78
Description	Change in apolipoprotein B (ApoB) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame	week 0, week 78

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	198	184
Mean (Standard Deviation) [g/L]	-0.08 (0.176)	-0.07 (0.192)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.08
	Confidence Interval	() 95%; -0.105 to -0.056
	Parameter Dispersion	Type: Standard Deviation; Value: 0.176
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Exenatide -> Liraglutide -> Liraglutide
	Comments	The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78- µ0=0 against HA: µ78 - µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Paired t test
	Comments
Method of Estimation	Estimation Parameter	Mean
	Estimated Value	-0.07
	Confidence Interval	() 95%; -0.094 to -0.038
	Parameter Dispersion	Type: Standard Deviation; Value: 0.192
	Estimation Comments

54. Secondary Outcome

Title	Hypoglycaemic Episodes at Week 26
Description	Total number of hypoglycaemic episodes occurring after baseline (week 0) and until week 26 (end of randomisation). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose was below 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.
Time Frame	weeks 0-26

Outcome Measure Data

Analysis Population Description

The safety analysis set is all subjects who had been exposed to at least one dose of the study products.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	235	232
Major	0	2
Minor	208	264
Symptoms only	79	93

55. Secondary Outcome

Title	Hypoglyceamic Episodes, Weeks 26-78
Description	Total number of hypoglycaemic episodes occurring after end of randomisation (week 26) and until week 78 (end of treatment). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose was below 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.
Time Frame	weeks 26-78

Outcome Measure Data

Analysis Population Description

The safety analysis set is all subjects who had been exposed to at least one dose of the study products.

Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide	Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)	Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Measure Participants	202	187
Major	1	0
Minor	140	172
Symptoms only	37	32

Adverse Events

Time Frame	The adverse events were collected in a time span of 78 weeks.
Adverse Event Reporting Description	The safety analysis set included all subjects who had been exposed to at least one dose of the study products.
Arm/Group Title	Liraglutide -> Liraglutide -> Liraglutide		Exenatide -> Liraglutide -> Liraglutide
Arm/Group Description	Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)		Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
All Cause Mortality
	Liraglutide -> Liraglutide -> Liraglutide		Exenatide -> Liraglutide -> Liraglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Liraglutide -> Liraglutide -> Liraglutide		Exenatide -> Liraglutide -> Liraglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/235 (9.8%)		23/232 (9.9%)
Blood and lymphatic system disorders
Haemorrhagic anaemia	0/235 (0%)	0	1/232 (0.4%)	1
Cardiac disorders
Acute coronary syndrome	1/235 (0.4%)	1	0/232 (0%)	0
Acute myocardial infarction	1/235 (0.4%)	1	1/232 (0.4%)	1
Angina pectoris	0/235 (0%)	0	1/232 (0.4%)	1
Cardiac artery disease	0/235 (0%)	0	1/232 (0.4%)	1
Cardiac failure	0/235 (0%)	0	1/232 (0.4%)	1
Cardiac failure congestive	1/235 (0.4%)	1	0/232 (0%)	0
Coronary artery occlusion	1/235 (0.4%)	1	0/232 (0%)	0
Coronary artery stenosis	1/235 (0.4%)	1	0/232 (0%)	0
Myocardial infarction	1/235 (0.4%)	1	2/232 (0.9%)	2
Supraventricular tachycardia	1/235 (0.4%)	2	0/232 (0%)	0
Endocrine disorders
Autoimmune thyroiditis	1/235 (0.4%)	1	0/232 (0%)	0
Goitre	1/235 (0.4%)	1	0/232 (0%)	0
Hyperthyroidism	0/235 (0%)	0	1/232 (0.4%)	1
Eye disorders
Cataract	0/235 (0%)	0	3/232 (1.3%)	3
Diplopia	1/235 (0.4%)	1	0/232 (0%)	0
Gastrointestinal disorders
Inguinal hernia	0/235 (0%)	0	1/232 (0.4%)	1
Intra-abdominal haematoma	0/235 (0%)	0	1/232 (0.4%)	1
Pancreatitis acute	1/235 (0.4%)	1	0/232 (0%)	0
General disorders
Chest discomfort	0/235 (0%)	0	1/232 (0.4%)	1
Non-cardiac chest pain	0/235 (0%)	0	1/232 (0.4%)	1
Hepatobiliary disorders
Cholelithiasis	1/235 (0.4%)	1	0/232 (0%)	0
Portal vein thrombosis	1/235 (0.4%)	1	0/232 (0%)	0
Infections and infestations
Campylobacter gastroenteritis	1/235 (0.4%)	1	0/232 (0%)	0
Cellulitis	0/235 (0%)	0	1/232 (0.4%)	1
Diverticulitis	1/235 (0.4%)	1	0/232 (0%)	0
Epstein-Barr virus infection	1/235 (0.4%)	1	0/232 (0%)	0
Lobar pneumonia	0/235 (0%)	0	1/232 (0.4%)	1
Lower respiratory tract infection	0/235 (0%)	0	1/232 (0.4%)	1
Moraxella infection	0/235 (0%)	0	1/232 (0.4%)	1
Pneumonia	1/235 (0.4%)	1	0/232 (0%)	0
Injury, poisoning and procedural complications
Jaw fracture	0/235 (0%)	0	1/232 (0.4%)	1
Lumbar vertebral fracture	0/235 (0%)	0	1/232 (0.4%)	1
Rib fracture	0/235 (0%)	0	1/232 (0.4%)	1
Tibia fracture	0/235 (0%)	0	1/232 (0.4%)	1
Investigations
Intraocular pressure increased	1/235 (0.4%)	1	0/232 (0%)	0
Metabolism and nutrition disorders
Hypoglycaemia	0/235 (0%)	0	1/232 (0.4%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	0/235 (0%)	0	1/232 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas	1/235 (0.4%)	1	0/232 (0%)	0
Brain neoplasm	1/235 (0.4%)	1	0/232 (0%)	0
Lung adenocarcinoma	1/235 (0.4%)	1	0/232 (0%)	0
Multiple myeloma	0/235 (0%)	0	1/232 (0.4%)	1
Neoplasm prostate	0/235 (0%)	0	1/232 (0.4%)	1
Rectal cancer	1/235 (0.4%)	1	0/232 (0%)	0
Nervous system disorders
Cerebellar infarction	1/235 (0.4%)	1	0/232 (0%)	0
Cerebral infarction	1/235 (0.4%)	1	0/232 (0%)	0
Cerebrovascular accident	1/235 (0.4%)	1	1/232 (0.4%)	1
Sciatica	1/235 (0.4%)	1	0/232 (0%)	0
Transient ischaemic attack	1/235 (0.4%)	1	0/232 (0%)	0
Psychiatric disorders
Bipolar disorder	1/235 (0.4%)	1	0/232 (0%)	0
Renal and urinary disorders
Nephrolithiasis	0/235 (0%)	0	1/232 (0.4%)	1
Reproductive system and breast disorders
Postmenopausal haemorrhage	1/235 (0.4%)	1	0/232 (0%)	0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/235 (0%)	0	1/232 (0.4%)	3
Dyspnoea	0/235 (0%)	0	1/232 (0.4%)	1
Nasal polyps	0/235 (0%)	0	1/232 (0.4%)	1
Pleurisy	1/235 (0.4%)	1	0/232 (0%)	0
Pulmonary embolism	1/235 (0.4%)	1	0/232 (0%)	0
Surgical and medical procedures
Blood product transfusion	0/235 (0%)	0	1/232 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Liraglutide -> Liraglutide -> Liraglutide		Exenatide -> Liraglutide -> Liraglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	162/235 (68.9%)		167/232 (72%)
Gastrointestinal disorders
Constipation	18/235 (7.7%)	18	10/232 (4.3%)	13
Diarrhoea	35/235 (14.9%)	47	37/232 (15.9%)	50
Dyspepsia	25/235 (10.6%)	35	14/232 (6%)	17
Nausea	64/235 (27.2%)	87	68/232 (29.3%)	92
Vomiting	19/235 (8.1%)	20	26/232 (11.2%)	31
Infections and infestations
Bronchitis	15/235 (6.4%)	18	20/232 (8.6%)	22
Influenza	13/235 (5.5%)	14	11/232 (4.7%)	11
Nasopharyngitis	43/235 (18.3%)	59	42/232 (18.1%)	71
Sinusitis	12/235 (5.1%)	14	9/232 (3.9%)	13
Upper respiratory tract infection	26/235 (11.1%)	33	28/232 (12.1%)	30
Metabolism and nutrition disorders
Anorexia	10/235 (4.3%)	10	12/232 (5.2%)	12
Musculoskeletal and connective tissue disorders
Back pain	22/235 (9.4%)	30	12/232 (5.2%)	13
Nervous system disorders
Dizziness	14/235 (6%)	16	9/232 (3.9%)	9
Headache	29/235 (12.3%)	38	28/232 (12.1%)	40
Vascular disorders
Hypertension	10/235 (4.3%)	10	12/232 (5.2%)	12

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Novo Nordisk maintains the right to be informed of any investigator plans for publication and to review any scientific paper, presentation, communication or other information concerning the investigation described in this protocol. Any such communication must be submitted in writing to the Novo Nordisk trial manager prior to submission for comments. Comments will be given within four weeks from receipt of the planned communication.