A Research Study to Look Into How Semaglutide, Together With a Lower Dose of Insulin Glargine, Compares to a Higher Dose of Insulin Glargine Alone in People With Type 2 Diabetes (SUSTAIN OPTIMIZE)

Sponsor

Novo Nordisk A/S (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05514535

Collaborator

(none)

568

Enrollment

Locations

Arms

16.1

Anticipated Duration (Months)

19.6

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study compares semaglutide, together with a lower dose of insulin glargine, to a higher dose of insulin glargine in participants with type 2 diabetes. The study looks at how well the study medicines control blood glucose levels. Participants will either get semaglutide together with a lower dose of insulin glargine or a higher dose of insulin glargine. The study will last for about 47 weeks (approximately 11 months). Participants will have 9 clinic visits, 15 phone/video calls and 1 home visit. Participants will be asked to wear a sensor that measures their blood sugar all the time in 2 periods of 10 days during the study.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2 Obesity	Drug: Semaglutide Drug: Insuline glargine (reduced) Drug: Insuline glargine (titrated)	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

568 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy and Safety of Once-weekly Semaglutide S.C. 2.0 mg as Add-on to Dose-reduced Insulin Glargine vs Titrated Insulin Glargine in Participants With Type 2 Diabetes and Overweight

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Jun 22, 2023

Anticipated Study Completion Date :

Jan 5, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Insuline glargine (reduced) + semaglutide Participants will initially receive 0.25 milligrams (mg) once-weekly semaglutide subcutaneously (s.c.) and the dose will be gradually escalated to 2 mg as an add-on to dose-reduced insulin glargine s.c. given once-daily. Insulin glargine 100 units will be reduced by 10 units at initiation of semaglutide and then again at each semaglutide dose escalation. Insulin glargine dose will be adjusted based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values (target SMPG: 4.4-7.2 millimoles per litre (mmol/L)).	Drug: Semaglutide Participants will receive once-weekly semaglutide s.c. for 40 weeks. Semaglutide 0.25 mg will be given at week 0 and then the dose will be escalated at weeks 4, 8 and 12 to 0.5 mg, 1 mg, 2 mg respectively. Drug: Insuline glargine (reduced) Participants will receive insulin glargine s.c. 100 units once-daily. Insulin glargine dose will be reduced by 10 units at initiation of semaglutide and then again at each semaglutide dose escalation up to 40 weeks. The dose will be adjusted based on the mean of three pre-breakfast SMPG values (target SMPG: 4.4-7.2 mmol/L).
Active Comparator: Insuline glargine (titrated) Participants will receive titrated insuline glargine s.c. 100 units once-daily. Insulin glargine dose will be adjusted based on the mean of three pre-breakfast SMPG values (target SMPG: 4.4-7.2 mmol/L).	Drug: Insuline glargine (titrated) Participants will receive titrated insulin glargine s.c. 100 units once-daily up to 40 weeks. The dose will be adjusted based on the mean of three pre-breakfast SMPG values (target SMPG: 4.4-7.2 mmol/L).

Arm

Intervention/Treatment

Experimental: Insuline glargine (reduced) + semaglutide

Participants will initially receive 0.25 milligrams (mg) once-weekly semaglutide subcutaneously (s.c.) and the dose will be gradually escalated to 2 mg as an add-on to dose-reduced insulin glargine s.c. given once-daily. Insulin glargine 100 units will be reduced by 10 units at initiation of semaglutide and then again at each semaglutide dose escalation. Insulin glargine dose will be adjusted based on the mean of three pre-breakfast self-measured plasma glucose (SMPG) values (target SMPG: 4.4-7.2 millimoles per litre (mmol/L)).

Drug: Semaglutide

Participants will receive once-weekly semaglutide s.c. for 40 weeks. Semaglutide 0.25 mg will be given at week 0 and then the dose will be escalated at weeks 4, 8 and 12 to 0.5 mg, 1 mg, 2 mg respectively.

Drug: Insuline glargine (reduced)

Participants will receive insulin glargine s.c. 100 units once-daily. Insulin glargine dose will be reduced by 10 units at initiation of semaglutide and then again at each semaglutide dose escalation up to 40 weeks. The dose will be adjusted based on the mean of three pre-breakfast SMPG values (target SMPG: 4.4-7.2 mmol/L).

Active Comparator: Insuline glargine (titrated)

Participants will receive titrated insuline glargine s.c. 100 units once-daily. Insulin glargine dose will be adjusted based on the mean of three pre-breakfast SMPG values (target SMPG: 4.4-7.2 mmol/L).

Drug: Insuline glargine (titrated)

Participants will receive titrated insulin glargine s.c. 100 units once-daily up to 40 weeks. The dose will be adjusted based on the mean of three pre-breakfast SMPG values (target SMPG: 4.4-7.2 mmol/L).

Outcome Measures

Primary Outcome Measures

Change in Glycated Haemoglobin (HbA1c) [From baseline (week 0) to end of treatment (week 40)]
Non-inferiority of semaglutide s.c. as add-on to dose-reduced insulin glargine to that of titrated insulin glargine will be assessed based on the clinically acceptable margin of 0.3 percentage (%) for the mean treatment difference in HbA1c. Measured as percentage.

Secondary Outcome Measures

Change in Body Weight [From baseline (week 0) to end of treatment (week 40)]
Measured as kilogram
Relative Change in Daily Insulin Dose [From baseline (week 0) to end of treatment (week 40)]
Measured as percentage
Change in HbA1c [From baseline (week 0) to end of treatment (week 40)]
Superiority of semaglutide s.c. as add-on to dose-reduced insulin glargine versus titrated insulin glargine will be assessed. Measured as percentage.
Score of Diabetes Treatment Satisfaction Questionnaire - Change Version (DTSQc) [At end of treatment (week 40)]
The questionnaire has been designed to measure the change in the level of satisfaction with diabetes treatment regimens in participants with diabetes who have had a recent intervention. It consists of 8 questions, which are to be answered on a Likert scale from -3 to +3 (-3 = much less satisfied now to +3 = much more satisfied now), with 0 (midpoint), representing no change. Six questions are summed to produce a total treatment satisfaction score. The remaining two questions concern perceived frequency of hyperglycemia and perceived frequency of hypoglycemia, respectively. The DTSQc total treatment satisfaction score ranges from -18 to +18, with higher scores associated with greater treatment satisfaction. Measured as score on a scale.
Participants Achieving: Insulin Dose Equal to 0 Units (Yes/No) [At end of treatment (week 40)]
Measured as count of participants
Participants Achieving: Insulin Dose Reduced From Baseline by at Least 50 Percentage (Yes/No) [At end of treatment (week 40)]
Measured as count of participants
Participants Achieving: HbA1c less than 7 Percentage (Yes/No) [At end of treatment (week 40)]
Measured as count of participants
Number of Severe Hypoglycaemic Episodes (Level 3) [From baseline (week 0) to end of treatment (week 40)]
Measured as number of episodes
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 Millimoles Per Litre (mmol/L) [54 Milligrams Per Decilitre (mg/dL)] Confirmed by Blood Glucose Meter) [From baseline (week 0) to end of treatment (week 40)]
Measured as number of episodes
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL), Confirmed by Blood Glucose Meter) or Severe Hypoglycaemic Episodes (Level 3) [From baseline (week 0) to end of treatment (week 40)]
Measured as number of episodes
Participants Achieving All of The Following Targets: HbA1c Reduced From Baseline by At Least 0.3 %; Insulin Dose Reduced From Baseline; No Hypoglycaemic Episodes; No Weight Gain [At end of treatment (week 40)]
No hypoglycaemic episodes defined as less than 3.9 mmol/L [70 milligrams per decilitre (mg/dL)] confirmed by Blood Glucose meter. Outcome measure measured as count of participants.
Change in Score of Diabetes Treatment Satisfaction Questionnaire - Status Version (DTSQs) [From baseline (week 0) to end of treatment (week 40)]
The questionnaire has been designed to measure satisfaction with diabetes treatment regimens in participants with diabetes. The questionnaire contains 8 components and measures the treatment for diabetes (including insulin, tablets and/or diet) in terms of convenience, flexibility and general feelings regarding treatment. The value presented is the 'Treatment Satisfaction' summary score, which is the sum of 6 of the 8 items of the DTSQs questionnaire. Response options range from 6 (best case) to 0 (worst case). Total scores for treatment satisfaction range from 0-36. Higher scores indicate higher satisfaction. Measured as score on a scale.
Change in Score of Short Form 36 Version 2 (SF-36 v2) [From baseline (week 0) to end of treatment (week 40)]
The SF-36 v2 will be used to measure differences in quality of life and mental wellbeing. The scores 0-100 (where higher scores indicated a better quality of life and mental wellbeing) from the SF-36 will be converted to a norm-based score using a T-score transformation in order to obtain a direct interpretation in relation to the distribution of the scores in the 1998 United States general population. Measured as score on a scale.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosed with Type 2 Diabetes Mellitus (T2D) mellitus greater than or equal to (>=) 180 days before screening.
Glycated haemoglobin (HbA1c) of 7-9 percentage [(53-75 millimoles per mole (mmol/mol)] (both inclusive) as assessed by central laboratory on the day of screening.
Body mass index (BMI) greater than or equal to (>=) 25 kilograms per meter square (kg/m^2) on the day of screening.
Stable daily dose(s) greater than or equal to (>=) 90 days before screening of any of the following anti-diabetic drugs or combination regimens:
Any metformin formulations greater than or equal to (>=) 1500 milligrams (mg) or maximum tolerated or effective dose.
Any metformin combination formulation greater than or equal to (>=) 1500 mg or maximum tolerated or effective dose.

The treatment can be with or without sodium glucose cotransporter 2 (SGLT-2) inhibitors.

• Treated with once daily insulin glargine Unit 100 injections less than or equal to (<=) 40 units/day greater than or equal to (>=) 90 days before screening. Short-term bolus insulin treatment for a maximum of 14 days before screening is allowed.

Exclusion Criteria:

Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
Potentially missed diagnosis of Type 1 diabetes (T1D) or latent autoimmune diabetes in adults (LADA) verified by C-peptide less than 0.5 nanomoles per litre (nmol/L) [1.5 nanograms per millilitre (ng/mL)] or antibodies to glutamic acid decarboxylase (anti-GAD) greater than 5 units/millilitre, as measured by the central laboratory at screening.
Presence or history of pancreatitis (acute or chronic).
Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of less than 30 millilitre per minute per 1.73 meter square at screening as defined by Kidney Disease: Improving Global Outcomes (KDIGO) 2012 classification.
Any episodes of diabetic ketoacidosis within 90 days before screening.
Known hypoglycaemic unawareness as indicated by the investigator according to Clarke's questionnaire question 8.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	New Port Richey	Florida	United States	34652
2	Novo Nordisk Investigational Site	West Des Moines	Iowa	United States	50265
3	Novo Nordisk Investigational Site	Morehead City	North Carolina	United States	28557
4	Novo Nordisk Investigational Site	Fargo	North Dakota	United States	58104
5	Novo Nordisk Investigational Site	Maumee	Ohio	United States	43537
6	Novo Nordisk Investigational Site	Kingsport	Tennessee	United States	37660
7	Novo Nordisk Investigational Site	Dallas	Texas	United States	75208
8	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
9	Novo Nordisk Investigational Site	Winchester	Virginia	United States	22601
10	Novo Nordisk Investigational Site	Alexandroupolis		Greece	GR-68100
11	Novo Nordisk Investigational Site	Athens		Greece	GR-11527
12	Novo Nordisk Investigational Site	Haidari-Athens		Greece	GR-12462
13	Novo Nordisk Investigational Site	Nikaia		Greece	GR-18454
14	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-54636
15	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-54643
16	Novo Nordisk Investigational Site	Catanzaro		Italy	88100
17	Novo Nordisk Investigational Site	Rome		Italy	00168
18	Novo Nordisk Investigational Site	Bratislava		Slovakia	83103
19	Novo Nordisk Investigational Site	Levice		Slovakia	93401
20	Novo Nordisk Investigational Site	Nove Zamky		Slovakia	940 59
21	Novo Nordisk Investigational Site	Poprad		Slovakia	05801
22	Novo Nordisk Investigational Site	Presov		Slovakia	080 01
23	Novo Nordisk Investigational Site	Prievidza		Slovakia	97101
24	Novo Nordisk Investigational Site	Sturovo		Slovakia	943 01
25	Novo Nordisk Investigational Site	Benoni	Gauteng	South Africa	1501
26	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	1501
27	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	2198
28	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal	South Africa	4450
29	Novo Nordisk Investigational Site	Umkomaas	KwaZulu-Natal	South Africa	4170

Sponsors and Collaborators

Novo Nordisk A/S

Investigators

Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Novo Nordisk A/S

ClinicalTrials.gov Identifier:

NCT05514535

Other Study ID Numbers:

NN9535-4801
U1111-1267-0312
2021-004392-13

First Posted:

Aug 24, 2022

Last Update Posted:

Aug 24, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Diabetes Mellitus

Diabetes Mellitus, Type 2

Insulin Glargine

Study Results

No Results Posted as of Aug 24, 2022