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)

Novo Nordisk A/S573 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

573

Conditions

Diabetes Mellitus, Type 2 Obesity

Interventions

Insuline glargine U100 (reduced)DRUG

Participants will receive insulin glargine U100 s.c. once-daily. Insulin glargine dose will be reduced by 10 U 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).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (239)

Shoals Primary Care

Sheffield, Alabama, United States

Lenzmeier Fam Med CCT Research

Glendale, Arizona, United States

Synexus Clinical Research US, Inc./Desert Clinical Research,

Mesa, Arizona, United States

OneLife Direct Care Inc.

Searcy, Arkansas, United States

Unity Health-Searcy Medical Center

Searcy, Arkansas, United States

Outcomes

Primary Outcomes

Change in Glycated Haemoglobin (HbA1c) [Noninferiority]

Change in HbA1c (Noninferiority) from baseline (Week 0) to end of treatment (Week 40) were reported. Here noninferiority was assessed based on the clinically acceptable margin of 0.3%-point for the mean treatment difference in HbA1c.

Time frame: From baseline (week 0) to end of treatment (week 40)

Secondary Outcomes

Change in Body Weight

Change in body weight from baseline (Week 0) to end of treatment (Week 40) were reported. Body weight was measured in unit 'Kilogram (kg)'.

Time frame: From baseline (week 0) to end of treatment (week 40)

Percentage Change in Daily Insulin Dose

Percentage change in daily insulin dose from baseline (Week 0) to end of treatment (Week 40) were reported. Percentage change from baseline to week 40 in insulin dose (%) was calculated as: (\[insulin dose at week 40\] - \[insulin dose at baseline\]) / \[insulin dose at baseline\] × 100.

Time frame: From baseline (week 0) to end of treatment (week 40)

Change in Glycated Haemoglobin (HbA1c ) [Superiority]

Change in HbA1c (Superiority) from baseline (Week 0) to end of treatment (Week 40) were reported.

Time frame: From baseline (week 0) to end of treatment (week 40)

Score of Diabetes Treatment Satisfaction Questionnaire - Change Version (DTSQc)

Score of Diabetes Treatment Satisfaction Questionnaire - change version (DTSQc) at end of treatment (week 40) were reported. The DTSQc provided a measure of how satisfied participants were with their current diabetes treatment compared with previous treatment. It consisted of 8 questions, which were 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. Out of 8 questions, 6 questions related to treatment satisfaction were summed to produce a total score. The DTSQc total treatment satisfaction score ranged from -18 to +18, with higher scores associated with greater treatment satisfaction.

Time frame: At end of treatment (week 40)

Number of Participants Achieving Insulin Dose = 0 Units/mL (U)

Number of participants achieving Insulin dose = 0 U at the end of treatment (Week 40) were reported.

Time frame: At end of treatment (week 40)

Number of Participants Achieving Insulin Dose Reduced From Baseline by at Least 50%

Number of participants achieving Insulin dose reduced from baseline by at least 50% by end pf treatment (Week 40) were reported.

Time frame: At end of treatment (week 40)

Number of Participants Achieving HbA1c Less Than (<) 7%

Number of participants achieving HbA1c \< 7% at the end of treatment (Week 40) were reported.

Time frame: At end of treatment (week 40)

Number of Severe Hypoglycaemic Episodes (Level 3)

Number of severe hypoglycaemic episodes (level 3) from baseline (week 0) to end of treatment (week 40) were reported. Severe hypoglycaemia (level 3) was defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery.

Time frame: From baseline (week 0) to end of treatment (week 40)

Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by Blood Glucose (BG) Meter)

Number of clinically significant hypoglycaemic episodes (level 2) (\<3.0 mmol/L (54 mg/dL), confirmed by BG meter) from baseline (week 0) to end of treatment (week 40) were reported. Clinically significant hypoglycaemia (level 2) was defined as plasma glucose value of less than (\<) 3.0 mmol/L (54 mg/dL) confirmed by BG meter.

Time frame: From baseline (week 0) to end of treatment (week 40)

Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3)

Number of clinically significant hypoglycaemic episodes (level 2) (\<3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3) from baseline (week 0) to end of treatment (week 40) were reported. Clinically significant hypoglycaemia (level 2) was defined as plasma glucose value of less than (\<) 3.0 mmol/L (54 mg/dL) confirmed by BG meter. Severe hypoglycaemia (level 3) was defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery.

Time frame: From baseline (week 0) to end of treatment (week 40)

Number of Participants Achieving HbA1c Reduced From Baseline by at Least 0.3%-Points and Insulin Dose Reduced From Baseline, No Hypoglycaemic Episodes (< 3.9 mmol/L (70 mg/dL) Confirmed by BG Meter) and No Weight Gain

Number of Participants achieving HbA1c reduced from baseline by at least 0.3%-points and Insulin dose reduced from baseline, No hypoglycaemic episodes (\< 3.9 mmol/L (70 mg/dL) confirmed by BG meter) and No weight gain at the end of treatment (Week 40) were reported.

Time frame: At end of treatment (week 40)

Change in Score of Diabetes Treatment Satisfaction Questionnaire - Status Version (DTSQs)

Score of Diabetes Treatment Satisfaction Questionnaire - status version (DTSQs) at end of treatment (week 40) were reported. The status version measures a patient's current satisfaction with treatment using a 0-6 scale for each item; higher scores indicate greater satisfaction with the present treatment (absolute/status level). The DTSQs total treatment satisfaction score ranged from 0 to 36, with higher scores associated with greater treatment satisfaction.

Time frame: From baseline (week 0) to end of treatment (week 40)

Change in Score of Short Form 36 Version 2 (SF-36 v2)

Change in SF-36 physical and mental component from baseline (week 0) to end of treatment (Week 40) were presented. SF-36 is self-administered questionnaire that measures each of following 8 health domains: physical functioning, role limitations due to physical problems (role-physical), social functioning, bodily pain, mental health, role limitations due to emotional problems (role-emotional), vitality, and general health perception. There are also 2 component scores derived from the 8 subscale scores: mental component summary and physical component summary. Physical component summary contains physical functioning, role-physical, bodily pain and general health and mental component summary contain vitality, social functioning, role-emotional and mental health. Each SF-36 domain and component summary score ranges from 0 to 100, higher scores reflect better participant health status. A positive change score indicates an improvement since baseline.

Time frame: From baseline (week 0) to end of treatment (week 40)