Phase 3 · Semaglutide

NCT05514535 trial results

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

Change in Glycated Haemoglobin (HbA1c) [Noninferiority] (Percentage point of HbA1c), From baseline (week 0) to end of treatment (week 40). Insuline Glargine U100 (Reduced) + Semaglutide: -1.37; Insuline Glargine U100 (Titrated): -0.65.

Participants
573
Status
completed
Completed
2025-04-09
Sponsor
Novo Nordisk A/S

As posted on ClinicalTrials.gov (NCT05514535), updated at source May 11, 2026. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What NCT05514535 measured first

Change in Glycated Haemoglobin (HbA1c) [Noninferiority]Percentage point of HbA1c · From baseline (week 0) to end of treatment (week 40) · mean
Insuline Glargine U100 (Reduced) + Semaglutiden=276Insuline Glargine U100 (Titrated)n=272
-1.37(0.84)-0.65(0.92)
Side effects by arm

Side effects in NCT05514535

Percent of participants affected, From baseline (week 0) to the end of study (week 45). The most common events the registry lists.

EventINSULIN GLARGINE (REDUCED) + SEMAGLUTIDEINSULIN GLARGINE (TITRATED)
Any serious event5.9%5.3%
Nausea18.4%0.7%
Diarrhoea13.5%4.2%
Vomiting9.7%0.4%
Constipation8%0%
Decreased appetite7.3%0.7%
Secondary outcomes

What else it measured

Change in Body WeightKilograms · From baseline (week 0) to end of treatment (week 40) · mean
Insuline Glargine U100 (Reduced) + Semaglutiden=282Insuline Glargine U100 (Titrated)n=275
-7.97(5.62)0.39(4.08)
Percentage Change in Daily Insulin DosePercentage change of daily insulin dose · From baseline (week 0) to end of treatment (week 40) · mean
Insuline Glargine U100 (Reduced) + Semaglutiden=182Insuline Glargine U100 (Titrated)n=266
-15.11(87.25)103.42(142.38)
Change in Glycated Haemoglobin (HbA1c ) [Superiority]Percentage-point of HbA1c · From baseline (week 0) to end of treatment (week 40) · mean
Insuline Glargine U100 (Reduced) + Semaglutiden=276Insuline Glargine U100 (Titrated)n=272
-1.37(0.84)-0.65(0.92)
Score of Diabetes Treatment Satisfaction Questionnaire - Change Version (DTSQc)Score on a scale · At end of treatment (week 40) · mean
Insuline Glargine U100 (Reduced) + Semaglutiden=270Insuline Glargine U100 (Titrated)n=262
14.69(4.65)12.11(6.84)
Number of Participants Achieving Insulin Dose = 0 Units/mL (U)Participants · At end of treatment (week 40) · count of participants
Insuline Glargine U100 (Reduced) + Semaglutiden=288Insuline Glargine U100 (Titrated)n=284
370
Number of Participants Achieving Insulin Dose Reduced From Baseline by at Least 50%Participants · At end of treatment (week 40) · count of participants
Insuline Glargine U100 (Reduced) + Semaglutiden=288Insuline Glargine U100 (Titrated)n=284
1032
Number of Participants Achieving HbA1c Less Than (<) 7%Participants · At end of treatment (week 40) · count of participants
Insuline Glargine U100 (Reduced) + Semaglutiden=285Insuline Glargine U100 (Titrated)n=281
224111
Number of Severe Hypoglycaemic Episodes (Level 3)Episodes · From baseline (week 0) to end of treatment (week 40) · number
Insuline Glargine U100 (Reduced) + Semaglutiden=285Insuline Glargine U100 (Titrated)n=281
614
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by Blood Glucose (BG) Meter)Episodes · From baseline (week 0) to end of treatment (week 40) · number
Insuline Glargine U100 (Reduced) + Semaglutiden=285Insuline Glargine U100 (Titrated)n=281
1632
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)Episodes · From baseline (week 0) to end of treatment (week 40) · number
Insuline Glargine U100 (Reduced) + Semaglutiden=285Insuline Glargine U100 (Titrated)n=281
2246
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 GainParticipants · At end of treatment (week 40) · count of participants
Insuline Glargine U100 (Reduced) + Semaglutiden=285Insuline Glargine U100 (Titrated)n=281
1386
Change in Score of Diabetes Treatment Satisfaction Questionnaire - Status Version (DTSQs)Score on scale · From baseline (week 0) to end of treatment (week 40) · mean
Insuline Glargine U100 (Reduced) + Semaglutiden=265Insuline Glargine U100 (Titrated)n=262
4.56(7.04)2.17(7.04)
The trial

How NCT05514535 was run

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.

  • Insuline glargine U100 (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 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...
  • 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).
Who could join the trial

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.

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

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