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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)

Phase 3
Completed
Conditions
Diabetes Mellitus, Type 2
Obesity
Interventions
Drug: Insuline glargine U100 (titrated)
Drug: Insuline glargine U100 (reduced)
Registration Number
NCT05514535
Lead Sponsor
Novo Nordisk A/S
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
568
Inclusion Criteria
  • Diagnosed with Type 2 Diabetes Mellitus (T2D) mellitus greater than or equal to (>=) 180 days before screening.
  • Glycated haemoglobin (HbA1c) of 7-10 percentage [(53-86 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 a once daily basal insulin (e.g. insulin glargine Unit 100 or U300, neutral protamine hagedorn (NPH) insulin, insulin detemir, insulin degludec) less than or equal to (<=) 40 units/day (U/day) for 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 0.26 nanomoles per litre (nmol/L) (or 260 picomoles per liter [pmol/L] [0.78 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Insuline glargine U100 (titrated)Insuline glargine U100 (titrated)Participants will receive titrated insuline glargine U100 s.c. once-daily. Insulin glargine U100 dose will be adjusted based on the mean of three pre-breakfast SMPG values (target SMPG: 4.4-7.2 mmol/L).
Insuline glargine U100 (reduced) + semaglutideInsuline glargine U100 (reduced)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 U100 will be reduced by 10 U at the 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)).
Insuline glargine U100 (reduced) + semaglutideSemaglutideParticipants 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 U100 will be reduced by 10 U at the 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)).
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
Relative Change in Daily Insulin DoseFrom baseline (week 0) to end of treatment (week 40)

Measured as percentage

Number of Severe Hypoglycaemic Episodes (Level 3)From baseline (week 0) to end of treatment (week 40)

Measured as number of episodes

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.

Participants Achieving: Insulin Dose Equal to 0 Units (Yes/No)At end of treatment (week 40)

Measured as count of participants

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 GainAt 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 Body WeightFrom baseline (week 0) to end of treatment (week 40)

Measured as kilogram

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

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

Change in HbA1cFrom 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: HbA1c less than 7 Percentage (Yes/No)At end of treatment (week 40)

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.

Trial Locations

Locations (107)

San Fernando Valley Hlth Inst, LLC

🇺🇸

Canoga Park, California, United States

Valley Research

🇺🇸

Fresno, California, United States

First Valley Medical Group

🇺🇸

Lancaster, California, United States

Loma Linda Univ Hlth Cr Endo

🇺🇸

Loma Linda, California, United States

Velocity Clin Res Los Angeles

🇺🇸

Los Angeles, California, United States

Valley Clinical Trials, Inc.

🇺🇸

Northridge, California, United States

Wetlin Research Associates, Inc.

🇺🇸

San Diego, California, United States

Encore Medical Research LLC

🇺🇸

Hollywood, Florida, United States

Northeast Res Inst. Inc.

🇺🇸

Jacksonville, Florida, United States

Jacksonville Ctr For Clin Res

🇺🇸

Jacksonville, Florida, United States

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San Fernando Valley Hlth Inst, LLC
🇺🇸Canoga Park, California, United States

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