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Phase 3 N=573 Randomized Treatment

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)

Diabetes Mellitus, Type 2 · Obesity

Enrolled (actual)
573
Serious AEs
5.6%
Results posted
May 2026
Primary outcome: Primary: Change in Glycated Haemoglobin (HbA1c) [Noninferiority] — -1.37; -0.65 Percentage point of HbA1c

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Semaglutide (Drug); Insuline glargine U100 (reduced) (Drug); Insuline glargine U100 (titrated) (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Novo Nordisk A/S
Primary completion
Mar 2025

Outcome Measures

OutcomeResultp-value
PRIMARY
Change in Glycated Haemoglobin (HbA1c) [Noninferiority]
-1.37; -0.65
SECONDARY
Change in Body Weight
-7.97; 0.39
SECONDARY
Percentage Change in Daily Insulin Dose
-15.11; 103.42
SECONDARY
Change in Glycated Haemoglobin (HbA1c ) [Superiority]
-1.37; -0.65
SECONDARY
Score of Diabetes Treatment Satisfaction Questionnaire - Change Version (DTSQc)
14.69; 12.11
SECONDARY
Number of Participants Achieving Insulin Dose = 0 Units/mL (U)
37; 0
SECONDARY
Number of Participants Achieving Insulin Dose Reduced From Baseline by at Least 50%
103; 2
SECONDARY
Number of Participants Achieving HbA1c Less Than (<) 7%
224; 111
SECONDARY
Number of Severe Hypoglycaemic Episodes (Level 3)
6; 14
SECONDARY
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by Blood Glucose (BG) Meter)
16; 32
SECONDARY
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)
22; 46
SECONDARY
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
138; 6
SECONDARY
Change in Score of Diabetes Treatment Satisfaction Questionnaire - Status Version (DTSQs)
4.56; 2.17
SECONDARY
Change in Score of Short Form 36 Version 2 (SF-36 v2)
3.18; 0.12; 1.63; 0.93

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.

Eligibility Criteria

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 ( =) 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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT05514535). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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