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Phase 3 Completed N=1,210 Randomized Quadruple-blind Treatment

Research Study Investigating How Well Semaglutide Works in People With Type 2 Diabetes Suffering From Overweight or Obesity

Source: ClinicalTrials.gov NCT03552757 ↗
Enrolled (actual)
1,210
Serious AEs
9.0%
Results posted
Aug 2021
Primary outcomePrimary: Change in Body Weight (%) - Semaglutide 2.4 mg Versus Placebo — -9.9; -3.3; -10.7; -3.1 Percentage point of body weight — p=<0.0001
◆ Published Evidence
Highly cited
1,262citations · ~252 / year
Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial.
Lancet (London, England) · 2021 · Open access · High-confidence link

Summary

This study will look at the change in the participant's body weight from the start to the end of the study. This is to compare the effect on body weight in people taking semaglutide (a new medicine) and people taking "dummy" medicine. In addition to taking the study medicine, the participant will have talks with study staff about healthy food choices, how to be more physically active and what else the participant can do to lose weight. Overweight and obesity is associated with an increased risk of type 2 diabetes. Therefore, weight loss has shown to have a beneficial impact on the blood sugar levels. The participant will either get semaglutide or "dummy" medicine - which treatment the participant get is decided by chance. The participant will need to take 2 injections at the same time once a week. The study medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm. The study will last for about 1.5 years

Linked Publications (5)

  • Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial.
    Lancet (London, England) · 2021 · 1,262 citations · Open access · High-confidence link
  • Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial.
    Lancet (London, England) · 2018 · 796 citations · Likely link
  • Effects of Semaglutide on Albuminuria and Kidney Function in People With Overweight or Obesity With or Without Type 2 Diabetes: Exploratory Analysis From the STEP 1, 2, and 3 Trials.
    Diabetes care · 2023 · 87 citations · Open access · Likely link
  • Psychiatric Safety of Semaglutide for Weight Management in People Without Known Major Psychopathology: Post Hoc Analysis of the STEP 1, 2, 3, and 5 Trials.
    JAMA internal medicine · 2024 · 75 citations · Open access · Likely link
  • Proteomic signatures reflect effects of semaglutide treatment for MASH.
    JHEP reports : innovation in hepatology · 2025 · 5 citations · Open access · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
Change in Body Weight (%) - Semaglutide 2.4 mg Versus Placebo
-9.9; -3.3; -10.7; -3.1 <0.0001 sig
PRIMARY
Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Placebo
267; 107; 121; 269; 257; 94 <0.0001 sig
SECONDARY
Change in Body Weight (%) - Semaglutide 2.4 mg Versus Semaglutide 1.0 mg
-9.9; -7.2
SECONDARY
Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Semaglutide 1.0 mg
267; 217; 121; 163
SECONDARY
Change in Waist Circumference
-6.9; -9.7; -4.3
SECONDARY
Change in Body Weight (Kg)
-7.1; -9.9; -3.4
SECONDARY
Change in BMI
-2.6; -3.6; -1.2
SECONDARY
Participants Who Achieve (Yes/no): Body Weight Reduction ≥10%
109; 177; 31; 271; 211; 345
SECONDARY
Participants Who Achieve (Yes/no): Body Weight Reduction ≥15%
52; 100; 12; 328; 288; 364
SECONDARY
Participants Who Achieve (Yes/no): Body Weight Reduction ≥20%
18; 51; 6; 362; 337; 370
SECONDARY
Change in HbA1c (%)
-1.5; -1.7; -0.3
SECONDARY
Change in HbA1c (mmol/Mol)
-16.9; -18.7; -3.4
SECONDARY
Change in FPG (mg/dL)
-36.5; -37.9; -2.3
SECONDARY
Change in Fasting Serum Insulin
0.94; 0.90; 0.93
SECONDARY
Participants Who Achieve (Yes/no): HbA1c <7.0% (53 mmol/Mol)
272; 299; 99; 104; 82; 275
SECONDARY
Participants Who Achieve (Yes/no): HbA1c ≤6.5% (48 mmol/Mol)
226; 257; 58; 150; 124; 316
SECONDARY
Participants Who Achieve (Yes/no): Body Weight Reduction ≥10% and HbA1c <7.0%
105; 170; 25; 271; 211; 349
SECONDARY
Participants Who Achieve (Yes/no): Body Weight Reduction ≥15% and HbA1c <7.0%
49; 98; 11; 327; 283; 363
SECONDARY
Change in Systolic Blood Pressure
-3; -4; 0
SECONDARY
Change in Diastolic Blood Pressure
-1; -2; -1
SECONDARY
Change in Total Cholesterol
0.97; 0.99; 1.00
SECONDARY
Change in HDL Cholesterol
1.06; 1.07; 1.04
SECONDARY
Change in LDL Cholesterol
0.99; 1.00; 1.00
SECONDARY
Change in VLDL Cholesterol
0.82; 0.80; 0.92
SECONDARY
Change in Free Fatty Acids
0.85; 0.84; 1.01
SECONDARY
Change in Triglycerides
0.81; 0.79; 0.92
SECONDARY
Change in hsCRP
0.59; 0.50; 0.84
SECONDARY
Change in PAI-1 Activity
1.21; 1.06; 1.42
SECONDARY
Change in Short Form 36 v2.0 Acute (SF-36) (Physical Functioning Score)
2.1; 2.8; 0.8
SECONDARY
Change in SF-36 (All Scores Except Physical Functioning)
0.6; 0.8; 0.0; 0.4; 0.3; -0.4
SECONDARY
Change in IWQOL-Lite for CT (Physical Function Domain (5-items) Score)
8.5; 11.4; 4.9
SECONDARY
Change in IWQOL-Lite for CT (All Scores Except Physical Function)
7.6; 11.0; 4.4; 8.6; 9.6; 5.6
SECONDARY
Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score
88; 111; 68; 282; 265; 297
SECONDARY
Participants Who Achieve (Yes/no): Responder Definition Value for IWQOL-Lite for CT Physical Function Domain (5-items) Score
107; 131; 83; 262; 245; 282
SECONDARY
Number of TEAEs - Semaglutide 2.4 mg Versus Placebo
2197; 1388
SECONDARY
Number of SAEs - Semaglutide 2.4 mg Versus Placebo
71; 53
SECONDARY
Number of Treatment Emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemia Episodes - Semaglutide 2.4 mg Versus Placebo
51; 18
SECONDARY
Change in Pulse - Semaglutide 2.4 mg Versus Placebo
2; 0
SECONDARY
Change in Amylase - Semaglutide 2.4 mg Versus Placebo
1.24; 1.06
SECONDARY
Change in Lipase - Semaglutide 2.4 mg Versus Placebo
1.41; 0.99
SECONDARY
Change in Calcitonin - Semaglutide 2.4 mg Versus Placebo
0.94; 0.96

Eligibility Criteria

Inclusion Criteria

  • Male or female, age greater than or equal to 18 years at the time of signing informed consent
  • Body Mass Index (BMI) greater than or equal to 27 kg/m^2 '
  • History of at least one self-reported unsuccessful dietary effort to lose body weight
  • Diagnosed with type 2 diabetes (haemoglobin A1c 7-10% (53-86 mmol/mol) (both inclusive)) 180 days or longer prior to the day of screening

Exclusion Criteria

  • A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records
  • Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of less than 30 mL/min/1.73 m^2 (less than 60 ml/min/1.73 m^2 in subjects treated with Sodium-glucose Cotransporter 2 Inhibitors) according to chronic kidney disease (CKD)-Epidemiology Collaboration (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 pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or an equally qualified health care provider (e.g. optometrist) within the past 90 days prior to screening or in the period between screening and randomisation
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03552757) and the linked publication. 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. Informational only — not medical advice.

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