Phase 3 · Semaglutide

NCT05649137 trial results

Effect and Safety of Semaglutide 7.2 mg Once-weekly in Participants With Obesity and Type 2 Diabetes

Relative Change in Body Weight (Percentage (%) change in body weight), Baseline (week 0), End of treatment (week 72). Semaglutide 7.2 mg: -13.5; Semaglutide 2.4 mg: -10.7; Placebo: -4.0.

Participants: 512
Status: completed
Completed: 2024-12-13
Sponsor: Novo Nordisk A/S

As posted on ClinicalTrials.gov (NCT05649137), updated at source Apr 27, 2026. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What NCT05649137 measured first

Relative Change in Body WeightPercentage (%) change in body weight · Baseline (week 0), End of treatment (week 72) · mean

Semaglutide 7.2 mgn=291	Semaglutide 2.4 mgn=97	Placebon=95
-13.5(8.7)	-10.7(8.1)	-4.0(6.2)

Number of Participants Who Achieve Body Weight Reduction Greater Than or Equal to (>=) 5% (Yes/no)Participants · At week 72 · count of participants

Measure	Semaglutide 7.2 mgn=291	Semaglutide 2.4 mgn=97	Placebon=95
Yes	251	73	33
No	40	24	62

Side effects by arm

Side effects in NCT05649137

Percent of participants affected, From week 0 to week 81. The most common events the registry lists.

Event	Semaglutide 7.2 mg	Semaglutide 2.4 mg	Placebo
Any serious event	9.8%	10.7%	9.8%
Nausea	29%	28.2%	11.8%
Diarrhoea	18.2%	20.4%	8.8%
Constipation	14.7%	18.4%	4.9%
Vomiting	16.6%	13.6%	2.9%
Upper respiratory tract infection	5.5%	8.7%	4.9%
Dyspepsia	8.1%	3.9%	2%
Decreased appetite	6.8%	7.8%	4.9%
Eructation	3.6%	7.8%	1%
Headache	7.2%	7.8%	3.9%
Nasopharyngitis	2.9%	2.9%	7.8%
COVID-19	7.2%	4.9%	6.9%
Back pain	5.5%	6.8%	2.9%
Fatigue	6.8%	1.9%	4.9%
Sensitive skin	5.9%	1.9%	0%
Cataract	2.9%	5.8%	3.9%
Abdominal pain	5.2%	2.9%	2.9%
Arthralgia	5.2%	3.9%	3.9%

Secondary outcomes

What else it measured

Number of Participants Who Achieve Body Weight Reduction >= 10% (Yes/no)Participants · At week 72 · count of participants

Measure	Semaglutide 7.2 mgn=291	Semaglutide 2.4 mgn=97	Placebon=95
Yes	183	50	11
No	108	47	84

Number of Participants Who Achieve Body Weight Reduction >= 15% (Yes/no)Participants · At week 72 · count of participants

Measure	Semaglutide 7.2 mgn=291	Semaglutide 2.4 mgn=97	Placebon=95
Yes	120	28	7
No	171	69	88

Number of Participants Who Achieve Body Weight Reduction >= 20% (Yes/no)Participants · At week 72 · count of participants

Measure	Semaglutide 7.2 mgn=291	Semaglutide 2.4 mgn=97	Placebon=95
Yes	62	14	2
No	229	83	93

Change in Waist CircumferenceCentimeters (cm) · Baseline (week 0), End of treatment (week 72) · mean

Semaglutide 7.2 mgn=291	Semaglutide 2.4 mgn=97	Placebon=95
-12.6(10.5)	-10.6(8.4)	-6.5(10.6)

Change in Glycated Haemoglobin (HbA1c)Percentage of HbA1c · Baseline (week 0), End of treatment (week 72) · mean

Semaglutide 7.2 mgn=288	Semaglutide 2.4 mgn=96	Placebon=94
-1.8(1.2)	-1.7(1.0)	-0.3(1.3)

Change in Body WeightKilograms (kg) · Baseline (week 0), End of treatment (week 72) · mean

Semaglutide 7.2 mgn=291	Semaglutide 2.4 mgn=97	Placebon=95
-14.9(10.6)	-11.4(8.9)	-4.6(7.1)

Change in Body Mass Index (BMI)kilograms per meter square (kg/m^2) · Baseline (week 0), End of treatment (week 72) · mean

Semaglutide 7.2 mgn=291	Semaglutide 2.4 mgn=97	Placebon=95
-5.3(3.8)	-4.1(3.3)	-1.6(2.5)

Change in Systolic Blood PressureMillimeters of mercury (mmHg) · Baseline (week 0), End of treatment (week 72) · mean

Semaglutide 7.2 mgn=291	Semaglutide 2.4 mgn=97	Placebon=95
-8(13)	-7(15)	-3(13)

Change in Diastolic Blood PressuremmHg · Baseline (week 0), End of treatment (week 72) · mean

Semaglutide 7.2 mgn=291	Semaglutide 2.4 mgn=97	Placebon=95
-3(9)	-3(10)	-3(9)

Change in Total Cholesterol (Millimoles Per Liter [mmol/L]) - Ratio to BaselineRatio of total cholesterol · Baseline (week 0), End of treatment (week 72) · geometric mean

Semaglutide 7.2 mgn=286	Semaglutide 2.4 mgn=94	Placebon=94
0.96(23.0)	0.96(21.1)	0.97(28.3)

Change in Total Cholesterol (Milligrams Per Deciliter [mg/dL]) - Ratio to BaselineRatio of total cholesterol · Baseline (week 0), End of treatment (week 72) · geometric mean

Semaglutide 7.2 mgn=286	Semaglutide 2.4 mgn=94	Placebon=94
0.96(23.0)	0.96(21.1)	0.97(28.3)

Change in High-density Lipoprotein (HDL) Cholesterol (mmol/L) - Ratio to BaselineRatio of HDL cholesterol · Baseline (week 0), End of treatment (week 72) · geometric mean

Semaglutide 7.2 mgn=285	Semaglutide 2.4 mgn=92	Placebon=91
1.10(17.8)	1.06(13.5)	1.07(16.1)

The trial

How NCT05649137 was run

This study will look at how much weight participants will lose and how much blood sugar control they achieve from the start to the end of the study. The weight loss in participants taking the investigational high dose of semaglutide will be compared to the weight loss in people taking "dummy" medicine and a lower dose of semaglutide. In addition to taking the medicine, participants will have talks with study staff about healthy food choices and how to be more physically active. Participants will either get semaglutide or "dummy" medicine. Which treatment participants get is decided by chance. Participants are more likely (4 out of 5) to get semaglutide than the "dummy" medicine. The study medicine will be injected briefly, under skin, with a thin needle, typically in the stomach, thighs, or upper arms. After receiving first dose, the dose of semaglutide will be gradually increased until reaching the target dose. The study will last for about 1.5 years

Semaglutide 7.2 mg: Participants will receive once-weekly injection of semaglutide subcutaneously (s.c.) in 20 week dose escalation period with dose escalation (0.25 milligram \[mg\], 0.5 mg, 1.0 mg, 1.7 mg, 2.4 mg, and 7.2 mg) every fourth week. Treatment will be continued on the maintenance dose of 7.2 mg once-weekly for an additional 52 weeks until week 72.
Semaglutide 2.4 mg: Participants will receive once-weekly s.c. injection of semaglutide in 20 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment will be continued on the maintenance dose of 2.4 mg once-weekly for an additional 52 weeks until week 72.
Placebo: Participants will receive once-weekly s.c. injection of placebo matched to semaglutide for 72 weeks.

Who could join the trial

Inclusion Criteria: * Male or female. * Age above or equal to 18 years at the time of signing informed consent. * BMI greater than or equal to 30.0 kilograms per square meter (kg/m\^2). * Diagnosed with type 2 diabetes (T2D) greater than or equal to 180 days prior to the day of screening. * History of at least one self-reported unsuccessful dietary effort to lose body weight. * HbA1c 7.0-10.0 percent (53-86 millimoles per mole \[mmol/mol\]) (both inclusive) as measured by central laboratory at screening. Exclusion Criteria: * A self-reported change in body weight greater than 5 kilograms (kg) (11 pounds \[lbs\]) within 90 days before screening irrespective of medical records. * Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma. * Renal impairment with estimated Glomerular Filtration Rate (eGFR) less than 30 milliliters per minute per 1.73 square meter (30 mL/min/1.73 m\^2) (less than 45 mL/min/1.73 m\^2 in participants treated with Sodium-glucose Cotransporter-2 \[SGLT2i\]) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation as defined by Kidney Disease: Improving Global Outcomes (KDIGO) 2012 by the central laboratory at screening. * Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within 90 days before screening or in the period between screening and randomization. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Published papers

Papers from NCT05649137

Lingvay I, Bergenheim SJ, Buse JB, Freitas P, Garvey WT, Harder-Lauridsen NM, Rosenstock J, Sahu K, Wharton S; STEP UP T2D trial group. Once-weekly semaglutide 7.2 mg in adults with obesity and type 2 diabetes (STEP UP T2D): a randomised, controlled, phase 3b trial. Lancet Diabetes Endocrinol. 2025 Nov;13(11):935-948. doi: 10.1016/S2213-8587(25)00225-6. Epub 2025 Sep 14.

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

GLPcompare is an informational data platform, not a medical provider or pharmacy. Nothing here is medical advice, a diagnosis, or a recommendation to start, stop, or change any treatment. Data is aggregated from public sources and can be incomplete or out of date. Always confirm with a licensed clinician and the current FDA label.