GENERATION: Saxagliptin Compared to Glimepiride in Elderly Type 2 Diabetes Patients, With Inadequate Glycemic Control on Metformin

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01006603
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 957
• Locations: 131
• Arms: 2
• Duration (Months): 32
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will evaluate the efficacy and tolerability of saxagliptin compared to glimepiride in elderly patients with type 2 diabetes mellitus who have inadequate glycaemic control on metformin monotherapy.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Saxagliptin; Drug: Glimepiride	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 957 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 52-Week, Randomised, Double Blind, Active-Controlled, Multi-Centre Phase IIIb/IV Study to Evaluate the Efficacy and Tolerability of Saxagliptin Compared to Glimepiride in Elderly Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycaemic Control on Metformin Monotherapy
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Saxagliptin 5 mg	Drug: Saxagliptin; 5 mg, oral tablet, once daily; Other Names: Onglyza
Active Comparator: 2 Glimepiride 1 - 6 mg	Drug: Glimepiride; 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily; Other Names: Amaryl

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients Reaching HbA1c <7% After 52 Weeks of Treatment Without Confirmed or Severe Hypoglycaemia. [From week 0 to week 52.]

   Defined as obtained on or before the 8th day after the last dosing day, as determined by central laboratory. Safety analysis set. Confirmed hypoglycaemia defined as: any event defined as either a symptomatic event with blood glucose level <3 mmol/L (<54 mg/dL) and no need for external assistance, or an asymptomatic blood glucose measurement <3 mmol/L (<54 mg/dL). Major (or severe) hypoglycaemia defined as: symptomatic events requiring external assistance due to severe impairment in consciousness or behaviour, with or without blood glucose level <3 mmol/L (<54 mg/dL), but with prompt recovery after glucose or glucagon administration. These events may be associated with sufficient neuroglycopenia to induce seizure or coma. Plasma glucose measurements may not be available during such an event, but neurological recovery, attributable to the restoration of plasma glucose to normal, was considered sufficient evidence that the event was induced by a low plasma glucose concentration.

Secondary Outcome Measures

1. Proportion of Patients Having Experienced at Least One Hypoglycaemic Event (Confirmed or Severe) Over the 52-week Double-blind Treatment Period. [From week 0 to week 52.]

   Hypoglyceamic event defined as, Confirmed hypoglycaemia: any event defined as either a symptomatic event with blood glucose level <3 mmol/L (<54 mg/dL) and no need for external assistance, or an asymptomatic blood glucose measurement <3 mmol/L (<54 mg/dL). Major (or severe) hypoglycaemia: symptomatic events requiring external assistance due to severe impairment in consciousness or behaviour, with or without blood glucose level <3 mmol/L (<54 mg/dL), but with prompt recovery after glucose or glucagon administration. These events may be associated with sufficient neuroglycopenia to induce seizure or coma. Plasma glucose measurements may not be available during such an event, but neurological recovery, attributable to the restoration of plasma glucose to normal, was considered sufficient evidence that the event was induced by a low plasma glucose concentration. Safety analysis set.

2. Change From Baseline to Week 52 in HbA1c. [From week 0 to week 52.]

   Measured as the difference between the last on-treatment value (defined as obtained before or on the 8th day after the last dosing date), and the last pre-randomisation HbA1c value, as determined by central laboratory. Full analysis set.

3. Proportion of Patients Achieving a Therapeutic Glycaemic Response at Week 52 Defined as HbA1c <7.0% [From week 0 to week 52]

   Proportion of patients with their last on-treatment value (defined as obtained before or on the 8th day after the last dosing date), as determined by central laboratory, below the specified limits. Full analysis set.

4. Change From Baseline to Week 52 in Fasting Plasma Glucose (FPG) [From week 0 to week 52]

   Measured as the difference between the last on-treatment value (defined as obtained before or on the first day after the last dosing date)and the last pre-randomisation fasting plasma glucose value, as determined by central laboratory. Full analysis set.

5. Change From Baseline to Week 52 in Insulin [From week 0 to week 52]

   Measured as the difference between the last on-treatment value (defined as obtained before or on the first day after the last dosing date) and the last pre-randomisation fasting plasma insulin value, as determined by central laboratory. Full analysis set.

6. Change From Baseline to Week 52 in β-cell Function (as Measured by Homeostasis Model Assessment-β [HOMA-β] [From week 0 to week 52]

   β-cell function as estimated by the homeostasis model assessment (HOMA) model. Value is derived from FPG and fasting insulin; fasting insulin values below 2.074 μU/mL or above 57.595 μU/mL and FPG values below 3 mmol/L or above 25 mmol/L are excluded (as restricted by the calculation method used). Full analysis set.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Provision of informed consent prior to any study specific procedures

• Established clinical diagnosis of type 2 diabetes. Treatment with a stable metformin monotherapy, for at least 8 weeks prior to Visit 1

• HbA1c ≥7.0% and ≤9.0%

Exclusion Criteria:

• Type 1 diabetes, history of diabetic ketoacidosis or hyperosmolar non-ketonic coma. Current use of any injectable or oral antihyperglycemic agent excluding metformin.

• Renal impairment as defined by a creatinine clearance <60 mL/min

• Individuals who, in the opinion of the investigator, in which participation in this study may pose a significant risk to the patient and could render the patient unable to successfully complete the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Feldbach		Austria
2	Research Site	Graz		Austria
3	Research Site	Salzburg		Austria
4	Research Site	Vienna		Austria
5	Research Site	Wien		Austria
6	Research Site	Aalborg		Denmark
7	Research Site	Ans by		Denmark
8	Research Site	Kjellerup		Denmark
9	Research Site	Kolding		Denmark
10	Research Site	Norresundby		Denmark
11	Research Site	Roskilde		Denmark
12	Research Site	Roslev		Denmark
13	Research Site	Vaerlose		Denmark
14	Research Site	Viborg		Denmark
15	Research Site	Viby J		Denmark
16	Research Site	Harjavalta		Finland
17	Research Site	Helsinki		Finland
18	Research Site	Kuopio		Finland
19	Research Site	Kuusankoski		Finland
20	Research Site	Lahti		Finland
21	Research Site	Oulu		Finland
22	Research Site	Seinajoki		Finland
23	Research Site	Sipoo		Finland
24	Research Site	Tampere		Finland
25	Research Site	Turku		Finland
26	Research Site	Vantaa		Finland
27	Research Site	Vimpeli		Finland
28	Research Site	Chatellerault		France
29	Research Site	La Rochelle		France
30	Research Site	La Seyne Sur Mer		France
31	Research Site	Laval		France
32	Research Site	Seysses		France
33	Research Site	Strasbourg		France
34	Research Site	Tierce		France
35	Research Site	Hamburg	HH	Germany
36	Research Site	Augsburg		Germany
37	Research Site	Darmstadt		Germany
38	Research Site	Dresden		Germany
39	Research Site	Essen		Germany
40	Research Site	Gelnhausen		Germany
41	Research Site	Hamburg		Germany
42	Research Site	Magdeburg		Germany
43	Research Site	Mayen		Germany
44	Research Site	Munchen		Germany
45	Research Site	Neumunster		Germany
46	Research Site	Nurnberg		Germany
47	Research Site	Pirna		Germany
48	Research Site	Ratzeburg		Germany
49	Research Site	Reinfeld		Germany
50	Research Site	Sulzbach		Germany
51	Research Site	Athens		Greece
52	Research Site	Nikea		Greece
53	Research Site	Thessaloniki		Greece
54	Research Site	ACS		Hungary
55	Research Site	Balatonfured		Hungary
56	Research Site	Budapest		Hungary
57	Research Site	ERD		Hungary
58	Research Site	Gyongyos		Hungary
59	Research Site	Komarom		Hungary
60	Research Site	Milano	MI	Italy
61	Research Site	Palermo	PA	Italy
62	Research Site	Padova	PD	Italy
63	Research Site	Pordenone	PN	Italy
64	Research Site	Reggio Emilia	RE	Italy
65	Research Site	Chieti		Italy
66	Research Site	Napoli		Italy
67	Research Site	Roma		Italy
68	Research Site	Viterbo		Italy
69	Research Site	Guadalajara	Jalisco	Mexico
70	Research Site	Monterrey	Nuevo Leon	Mexico
71	Research Site	Durango		Mexico
72	Research Site	Aksdal		Norway
73	Research Site	Alesund		Norway
74	Research Site	Elverum		Norway
75	Research Site	Halden		Norway
76	Research Site	Hamar		Norway
77	Research Site	Kirkenaer		Norway
78	Research Site	Kongsvinger		Norway
79	Research Site	Larvik		Norway
80	Research Site	Lierskogen		Norway
81	Research Site	Nord-lenangen		Norway
82	Research Site	Oslo		Norway
83	Research Site	ROA		Norway
84	Research Site	Sandvika		Norway
85	Research Site	Skedsmokorset		Norway
86	Research Site	Sorumsand		Norway
87	Research Site	Svelvik		Norway
88	Research Site	Trondheim		Norway
89	Research Site	Ulset		Norway
90	Research Site	Sevilla	Andalucia	Spain
91	Research Site	Oviedo	Asturias	Spain
92	Research Site	Zamora	Castilla Y Leon	Spain
93	Research Site	Getafe	Comunidad de Madrid	Spain
94	Research Site	Madrid	Comunidad de Madrid	Spain
95	Research Site	San Sebastian de Los Reyes	Comunidad de Madrid	Spain
96	Research Site	Alicante	Comunidad Valenciana	Spain
97	Research Site	A Coruna	Galicia	Spain
98	Research Site	Begonte (lugo)	Galicia	Spain
99	Research Site	Finspang		Sweden
100	Research Site	Gavle		Sweden
101	Research Site	Goteborg		Sweden
102	Research Site	Jarfalla		Sweden
103	Research Site	Jonkoping		Sweden
104	Research Site	Lessebo		Sweden
105	Research Site	Lund		Sweden
106	Research Site	Odeshog		Sweden
107	Research Site	Pitea		Sweden
108	Research Site	Rattvik		Sweden
109	Research Site	Stockholm		Sweden
110	Research Site	Trollhattan		Sweden
111	Research Site	Vastervik		Sweden
112	Research Site	Fowey	Cornwall	United Kingdom
113	Research Site	Nr Penzance	Cornwall	United Kingdom
114	Research Site	Penzance	Cornwall	United Kingdom
115	Research Site	Barnstaple	Devon	United Kingdom
116	Research Site	Plymouth	Devon	United Kingdom
117	Research Site	Annan	Dumfries and Galloway	United Kingdom
118	Research Site	Canterbury	Kent	United Kingdom
119	Research Site	Whitstable	Kent	United Kingdom
120	Research Site	Frome	Somerset	United Kingdom
121	Research Site	Bradford-on-avon	Wiltshire	United Kingdom
122	Research Site	Trowbridge	Wiltshire	United Kingdom
123	Research Site	Ayrshire		United Kingdom
124	Research Site	Bath		United Kingdom
125	Research Site	Cumbernauld		United Kingdom
126	Research Site	Dundee		United Kingdom
127	Research Site	Hamilton		United Kingdom
128	Research Site	Middlesex		United Kingdom
129	Research Site	Motherwell		United Kingdom
130	Research Site	Somerset		United Kingdom
131	Research Site	Wellingborough		United Kingdom

Sponsors and Collaborators

• AstraZeneca
• Bristol-Myers Squibb

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01006603
• Other Study ID Numbers: D1680L00002
• First Posted: Nov 3, 2009
• Last Update Posted: Nov 28, 2013
• Last Verified: Sep 1, 2013

• Keywords provided by AstraZeneca: Type 2 Diabetes Mellitus; elderly patients; saxagliptin; randomised; double-blind
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Glimepiride; Saxagliptin

Study Results

Participant Flow

Recruitment Details	In total, 152 study centres in 13 countries recruited patients in this study. The first patient was enrolled in the study on 20 October 2009, and the last patient completed the study on 14 June 2012. 957 subjects were enrolled. 753 were deemed eligible for lead-in and 720 were randomized.
Pre-assignment Detail	A 2-week single-blind (to patient only) placebo lead-in period occurred from Week -2 to Week 0. Patients were from this period on,counselled on dietary and lifestyle modifications according to usual clinical routine. They were given a glucometer to check their plasma glucose at home at least every second day.

Arm/Group Title	Saxagliptin 5 mg	Glimepiride 1 - 6 mg
Arm/Group Description	Saxagliptin 5 mg, oral tablet, once daily	Glimepiride : 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily
Period Title: Overall Study
STARTED	360	360
COMPLETED	289	285
NOT COMPLETED	71	75

Baseline Characteristics

Arm/Group Title	Saxagliptin 5 mg	Glimepiride 1 - 6 mg	Total
Arm/Group Description	Saxagliptin 5 mg, oral tablet, once daily	Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily	Total of all reporting groups
Overall Participants	360	360	720
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	360 100%	360 100%	720 100%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.5 (5.72)	72.7 (5.44)	72.6 (5.58)
Sex: Female, Male (Count of Participants)
Female	143 39.7%	132 36.7%	275 38.2%
Male	217 60.3%	228 63.3%	445 61.8%
Region of Enrollment (participants) [Number]
Greece	21 5.8%	18 5%	39 5.4%
Finland	24 6.7%	19 5.3%	43 6%
Spain	31 8.6%	25 6.9%	56 7.8%
Austria	30 8.3%	15 4.2%	45 6.3%
United Kingdom	39 10.8%	49 13.6%	88 12.2%
Italy	12 3.3%	12 3.3%	24 3.3%
France	11 3.1%	13 3.6%	24 3.3%
Hungary	9 2.5%	9 2.5%	18 2.5%
Mexico	10 2.8%	7 1.9%	17 2.4%
Denmark	16 4.4%	17 4.7%	33 4.6%
Germany	44 12.2%	55 15.3%	99 13.8%
Norway	47 13.1%	59 16.4%	106 14.7%
Sweden	66 18.3%	62 17.2%	128 17.8%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients Reaching HbA1c <7% After 52 Weeks of Treatment Without Confirmed or Severe Hypoglycaemia.
Description	Defined as obtained on or before the 8th day after the last dosing day, as determined by central laboratory. Safety analysis set. Confirmed hypoglycaemia defined as: any event defined as either a symptomatic event with blood glucose level <3 mmol/L (<54 mg/dL) and no need for external assistance, or an asymptomatic blood glucose measurement <3 mmol/L (<54 mg/dL). Major (or severe) hypoglycaemia defined as: symptomatic events requiring external assistance due to severe impairment in consciousness or behaviour, with or without blood glucose level <3 mmol/L (<54 mg/dL), but with prompt recovery after glucose or glucagon administration. These events may be associated with sufficient neuroglycopenia to induce seizure or coma. Plasma glucose measurements may not be available during such an event, but neurological recovery, attributable to the restoration of plasma glucose to normal, was considered sufficient evidence that the event was induced by a low plasma glucose concentration.
Time Frame	From week 0 to week 52.

Outcome Measure Data

Analysis Population Description

Safety analysis set (a subset of the randomised analysis set including patients who took at least one investigational product dose).

Arm/Group Title	Saxagliptin 5 mg	Glimepiride 1 - 6 mg
Arm/Group Description	Saxagliptin 5 mg, oral tablet, once daily	Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily
Measure Participants	359	359
All patients	37.9 10.5%	38.2 10.6%
patients aged <75 years (n=217, n=216)	39.2 10.9%	33.3 9.3%
patients aged ≥75 years (n=142, n=143)	35.9 10%	45.5 12.6%

2. Secondary Outcome

Title	Proportion of Patients Having Experienced at Least One Hypoglycaemic Event (Confirmed or Severe) Over the 52-week Double-blind Treatment Period.
Description	Hypoglyceamic event defined as, Confirmed hypoglycaemia: any event defined as either a symptomatic event with blood glucose level <3 mmol/L (<54 mg/dL) and no need for external assistance, or an asymptomatic blood glucose measurement <3 mmol/L (<54 mg/dL). Major (or severe) hypoglycaemia: symptomatic events requiring external assistance due to severe impairment in consciousness or behaviour, with or without blood glucose level <3 mmol/L (<54 mg/dL), but with prompt recovery after glucose or glucagon administration. These events may be associated with sufficient neuroglycopenia to induce seizure or coma. Plasma glucose measurements may not be available during such an event, but neurological recovery, attributable to the restoration of plasma glucose to normal, was considered sufficient evidence that the event was induced by a low plasma glucose concentration. Safety analysis set.
Time Frame	From week 0 to week 52.

Outcome Measure Data

Analysis Population Description

Safety analysis set (a subset of the randomised analysis set including patients who took at least one investigational product dose).

Arm/Group Title	Saxagliptin 5 mg	Glimepiride 1 - 6 mg
Arm/Group Description	Saxagliptin 5 mg, oral tablet, once daily	Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily
Measure Participants	359	359
Number [percentage of patients]	1.1	15.3

3. Secondary Outcome

Title	Change From Baseline to Week 52 in HbA1c.
Description	Measured as the difference between the last on-treatment value (defined as obtained before or on the 8th day after the last dosing date), and the last pre-randomisation HbA1c value, as determined by central laboratory. Full analysis set.
Time Frame	From week 0 to week 52.

Outcome Measure Data

Analysis Population Description

The number of subjects with non-missing baseline and Week 52 (LOCF) values in the full analysis set (defined as the subset of patients in the randomized analysis set who took at least one randomised IP dose and have non-missing baseline and post-baseline efficacy data for at least one variable).

Arm/Group Title	Saxagliptin 5 mg	Glimepiride 1 - 6 mg
Arm/Group Description	Saxagliptin 5 mg, oral tablet, once daily	Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily
Measure Participants	353	345
Mean (95% Confidence Interval) [% of glycosylated hemoglobin]	-0.44	-0.64

4. Secondary Outcome

Title	Proportion of Patients Achieving a Therapeutic Glycaemic Response at Week 52 Defined as HbA1c <7.0%
Description	Proportion of patients with their last on-treatment value (defined as obtained before or on the 8th day after the last dosing date), as determined by central laboratory, below the specified limits. Full analysis set.
Time Frame	From week 0 to week 52

Outcome Measure Data

Analysis Population Description

The number of subjects with non-missing baseline and Week 52 (LOCF) values in the full analysis set (defined as the subset of patients in the randomized analysis set who took at least one randomised IP dose and have non-missing baseline and post-baseline efficacy data for at least one variable).

Arm/Group Title	Saxagliptin 5 mg	Glimepiride 1 - 6 mg
Arm/Group Description	Saxagliptin 5 mg, oral tablet, once daily	Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily
Measure Participants	356	353
Number [percentage of responders]	44.7	54.7

5. Secondary Outcome

Title	Change From Baseline to Week 52 in Fasting Plasma Glucose (FPG)
Description	Measured as the difference between the last on-treatment value (defined as obtained before or on the first day after the last dosing date)and the last pre-randomisation fasting plasma glucose value, as determined by central laboratory. Full analysis set.
Time Frame	From week 0 to week 52

Outcome Measure Data

Analysis Population Description

The number of subjects with non-missing baseline and Week 52 (LOCF) values in the full analysis set (defined as the subset of patients in the randomized analysis set who took at least one randomised IP dose and have non-missing baseline and post-baseline efficacy data for at least one variable).

Arm/Group Title	Saxagliptin 5 mg	Glimepiride 1 - 6 mg
Arm/Group Description	Saxagliptin 5 mg, oral tablet, once daily	Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily
Measure Participants	344	339
Mean (95% Confidence Interval) [mmol/L]	-0.73	-1.29

6. Secondary Outcome

Title	Change From Baseline to Week 52 in Insulin
Description	Measured as the difference between the last on-treatment value (defined as obtained before or on the first day after the last dosing date) and the last pre-randomisation fasting plasma insulin value, as determined by central laboratory. Full analysis set.
Time Frame	From week 0 to week 52

Outcome Measure Data

Analysis Population Description

The number of subjects with non-missing baseline and Week 52 (LOCF) values in the full analysis set (defined as the subset of patients in the randomized analysis set who took at least one randomised IP dose and have non-missing baseline and post-baseline efficacy data for at least one variable).

Arm/Group Title	Saxagliptin 5 mg	Glimepiride 1 - 6 mg
Arm/Group Description	Saxagliptin 5 mg, oral tablet, once daily	Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily
Measure Participants	312	309
Mean (95% Confidence Interval) [µU/mL]	-2.0	-0.6

7. Secondary Outcome

Title	Change From Baseline to Week 52 in β-cell Function (as Measured by Homeostasis Model Assessment-β [HOMA-β]
Description	β-cell function as estimated by the homeostasis model assessment (HOMA) model. Value is derived from FPG and fasting insulin; fasting insulin values below 2.074 μU/mL or above 57.595 μU/mL and FPG values below 3 mmol/L or above 25 mmol/L are excluded (as restricted by the calculation method used). Full analysis set.
Time Frame	From week 0 to week 52

Outcome Measure Data

Analysis Population Description

The number of subjects with non-missing baseline and Week 52 (LOCF) values in the full analysis set (defined as the subset of patients in the randomized analysis set who took at least one randomised IP dose and have non-missing baseline and post-baseline efficacy data for at least one variable).

Arm/Group Title	Saxagliptin 5 mg	Glimepiride 1 - 6 mg
Arm/Group Description	Saxagliptin 5 mg, oral tablet, once daily	Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily
Measure Participants	240	247
Mean (95% Confidence Interval) [percentage of change from baseline]	3.83	16.22

Adverse Events

Adverse Event Reporting Description	The at Risk population includes only those randomized subjects who took at least one dose of study drug.
Arm/Group Title	Saxagliptin 5 mg		Glimepiride 1 - 6 mg
Arm/Group Description	Saxagliptin 5 mg, oral tablet, once daily		Glimepiride 1, 2, 3, 4 or 6 mg, oral encapsulated tablet, once daily
All Cause Mortality
	Saxagliptin 5 mg		Glimepiride 1 - 6 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Saxagliptin 5 mg		Glimepiride 1 - 6 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/359 (11.4%)		32/359 (8.9%)
Blood and lymphatic system disorders
ANAEMIA	1/359 (0.3%)		0/359 (0%)
LYMPHADENOPATHY	0/359 (0%)		1/359 (0.3%)
Cardiac disorders
CARDIAC FAILURE	1/359 (0.3%)		3/359 (0.8%)
MYOCARDIAL INFARCTION	3/359 (0.8%)		1/359 (0.3%)
ACUTE MYOCARDIAL INFARCTION	0/359 (0%)		2/359 (0.6%)
ATRIAL FIBRILLATION	2/359 (0.6%)		1/359 (0.3%)
ANGINA PECTORIS	1/359 (0.3%)		1/359 (0.3%)
ANGINA UNSTABLE	1/359 (0.3%)		0/359 (0%)
ISCHAEMIC CARDIOMYOPATHY	1/359 (0.3%)		0/359 (0%)
PERICARDITIS	1/359 (0.3%)		0/359 (0%)
TACHYCARDIA	0/359 (0%)		1/359 (0.3%)
Gastrointestinal disorders
EPIGASTRIC DISCOMFORT	1/359 (0.3%)		0/359 (0%)
HIATUS HERNIA	1/359 (0.3%)		0/359 (0%)
INGUINAL HERNIA	1/359 (0.3%)		0/359 (0%)
MELAENA	1/359 (0.3%)		0/359 (0%)
SUBILEUS	0/359 (0%)		1/359 (0.3%)
General disorders
CHEST PAIN	1/359 (0.3%)		0/359 (0%)
DEATH	0/359 (0%)		1/359 (0.3%)
DEVICE DISLOCATION	1/359 (0.3%)		0/359 (0%)
INFLAMMATION	1/359 (0.3%)		0/359 (0%)
Hepatobiliary disorders
CHOLECYSTITIS	1/359 (0.3%)		0/359 (0%)
Immune system disorders
ANAPHYLACTIC SHOCK	1/359 (0.3%)		0/359 (0%)
Infections and infestations
PNEUMONIA	3/359 (0.8%)		3/359 (0.8%)
APPENDICITIS	1/359 (0.3%)		0/359 (0%)
DIVERTICULITIS	0/359 (0%)		1/359 (0.3%)
GASTROENTERITIS	0/359 (0%)		1/359 (0.3%)
GASTROENTERITIS NOROVIRUS	0/359 (0%)		1/359 (0.3%)
INFECTIOUS PLEURAL EFFUSION	0/359 (0%)		1/359 (0.3%)
LABYRINTHITIS	0/359 (0%)		1/359 (0.3%)
PYELONEPHRITIS	1/359 (0.3%)		0/359 (0%)
RESPIRATORY TRACT INFECTION	0/359 (0%)		1/359 (0.3%)
URINARY TRACT INFECTION	0/359 (0%)		1/359 (0.3%)
UROSEPSIS	1/359 (0.3%)		0/359 (0%)
Injury, poisoning and procedural complications
LUMBAR VERTEBRAL FRACTURE	2/359 (0.6%)		0/359 (0%)
ANKLE FRACTURE	0/359 (0%)		1/359 (0.3%)
CONCUSSION	1/359 (0.3%)		0/359 (0%)
CONTUSION	0/359 (0%)		1/359 (0.3%)
FEMUR FRACTURE	1/359 (0.3%)		0/359 (0%)
HAND FRACTURE	1/359 (0.3%)		0/359 (0%)
MUSCLE RUPTURE	0/359 (0%)		1/359 (0.3%)
Investigations
MEDICAL OBSERVATION	0/359 (0%)		1/359 (0.3%)
WEIGHT DECREASED	1/359 (0.3%)		0/359 (0%)
Metabolism and nutrition disorders
HYPERKALAEMIA	1/359 (0.3%)		0/359 (0%)
HYPOGLYCAEMIA	0/359 (0%)		1/359 (0.3%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	1/359 (0.3%)		0/359 (0%)
BACK PAIN	1/359 (0.3%)		0/359 (0%)
INTERVERTEBRAL DISC PROTRUSION	0/359 (0%)		1/359 (0.3%)
JOINT EFFUSION	0/359 (0%)		1/359 (0.3%)
OSTEOARTHRITIS	1/359 (0.3%)		0/359 (0%)
SPINAL COLUMN STENOSIS	1/359 (0.3%)		0/359 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BREAST CANCER	2/359 (0.6%)		0/359 (0%)
BASAL CELL CARCINOMA	1/359 (0.3%)		1/359 (0.3%)
BLADDER TRANSITIONAL CELL CARCINOMA	1/359 (0.3%)		0/359 (0%)
BREAST CANCER IN SITU	1/359 (0.3%)		0/359 (0%)
COLON CANCER	1/359 (0.3%)		0/359 (0%)
HEPATIC NEOPLASM MALIGNANT	1/359 (0.3%)		0/359 (0%)
LUNG CANCER METASTATIC	0/359 (0%)		1/359 (0.3%)
LYMPHOMA	1/359 (0.3%)		0/359 (0%)
PANCREATIC CARCINOMA	1/359 (0.3%)		0/359 (0%)
PROSTATE CANCER	0/359 (0%)		1/359 (0.3%)
SALIVARY GLAND CANCER	1/359 (0.3%)		0/359 (0%)
Nervous system disorders
CEREBROVASCULAR ACCIDENT	0/359 (0%)		1/359 (0.3%)
EPILEPSY	0/359 (0%)		1/359 (0.3%)
SYNCOPE	1/359 (0.3%)		1/359 (0.3%)
TRANSIENT ISCHAEMIC ATTACK	0/359 (0%)		1/359 (0.3%)
Renal and urinary disorders
CALCULUS BLADDER	1/359 (0.3%)		0/359 (0%)
CALCULUS URETERIC	0/359 (0%)		1/359 (0.3%)
NEUROGENIC BLADDER	0/359 (0%)		1/359 (0.3%)
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	1/359 (0.3%)		1/359 (0.3%)
DYSPNOEA	0/359 (0%)		1/359 (0.3%)
Surgical and medical procedures
SURGICAL AND MEDICAL PROCEDURES CARDIOVERSION Systematic Assessment 0 359 1 359	1/359 (0.3%)		0/359 (0%)
Vascular disorders
AORTIC ANEURYSM	1/359 (0.3%)		0/359 (0%)
AORTIC ARTERIOSCLEROSIS	0/359 (0%)		1/359 (0.3%)
CIRCULATORY COLLAPSE	0/359 (0%)		1/359 (0.3%)
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE	1/359 (0.3%)		0/359 (0%)
Other (Not Including Serious) Adverse Events
	Saxagliptin 5 mg		Glimepiride 1 - 6 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	130/359 (36.2%)		129/359 (35.9%)
Ear and labyrinth disorders
VERTIGO	9/359 (2.5%)		0/359 (0%)
Gastrointestinal disorders
DIARRHOEA	15/359 (4.2%)		19/359 (5.3%)
CONSTIPATION	4/359 (1.1%)		10/359 (2.8%)
NAUSEA	4/359 (1.1%)		8/359 (2.2%)
Infections and infestations
NASOPHARYNGITIS	23/359 (6.4%)		35/359 (9.7%)
URINARY TRACT INFECTION	11/359 (3.1%)		18/359 (5%)
BRONCHITIS	14/359 (3.9%)		7/359 (1.9%)
UPPER RESPIRATORY TRACT INFECTION	12/359 (3.3%)		14/359 (3.9%)
Injury, poisoning and procedural complications
CONTUSION	8/359 (2.2%)		0/359 (0%)
Musculoskeletal and connective tissue disorders
BACK PAIN	9/359 (2.5%)		18/359 (5%)
ARTHRALGIA	17/359 (4.7%)		9/359 (2.5%)
PAIN IN EXTREMITY	10/359 (2.8%)		9/359 (2.5%)
MUSCULOSKELETAL PAIN	9/359 (2.5%)		3/359 (0.8%)
Nervous system disorders
DIZZINESS	6/359 (1.7%)		17/359 (4.7%)
HEADACHE	6/359 (1.7%)		12/359 (3.3%)
TREMOR	1/359 (0.3%)		8/359 (2.2%)
Respiratory, thoracic and mediastinal disorders
COUGH	9/359 (2.5%)		13/359 (3.6%)
Vascular disorders
HYPERTENSION	8/359 (2.2%)		12/359 (3.3%)

Limitations/Caveats

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