Research Study Looking at How Well Semaglutide Works in People Living With Obesity and Prediabetes (STEP 10)

Efficacy and Safety of Subcutaneous Semaglutide 2.4 mg Once-weekly in Subjects With Obesity and Prediabetes

This study looks at how well a new medicine, called semaglutide, works at helping people with obesity and prediabetes.

This study will look at how much weight participants lose, and if participants can go from having blood sugar that is higher than normal (prediabetes) to having normal blood sugar.

Semaglutide is compared to a "dummy" medicine. The "dummy" medicine looks like semaglutide but has no effect on the body.

In addition to taking the medicine, participants will have talks with study staff about healthy food choices, how to be more physically active and what participants can do to lose weight.

Participants will either get semaglutide or "dummy" medicine - which treatment they get is decided by chance. Participants are 2 times as likely to get semaglutide as "dummy" medicine.

Participants will need to take 1 injection 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 19 months. Participants have to take the study medicine every week for the first 12 months. The last 7 months participants will not take any medication.

Participants will have 14 clinic visits and 1 phone call with the study staff. At 9 of the clinic visits Participants will have blood samples taken. Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Semaglutide 2.4 mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G1V 4G2
    • CHU de Quebec-Universite Laval
  • Québec, Canada, G1V 4G5
    • Institut universitaire de cardiologie
  • Alberta
    • Calgary, Alberta, Canada, T2T 5C7
      • University of Calgary
    • Calgary, Alberta, Canada, T2H 2G4
      • LMC Clin Res Inc. Calgary
    • Calgary, Alberta, Canada, T2V 4J2
      • C-endo Diab Endo Clin Calgery
    • Edmonton, Alberta, Canada, T6G 2R3
      • Weight Wise Clinic
  • British Columbia
    • Surrey, British Columbia, Canada, V3Z 2N6
      • Ocean West Research Clinic
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1G 1A7
      • G.A. Research Associates Ltd.
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Nova Scotia Hlth Halifax
  • Ontario
    • Barrie, Ontario, Canada, L4N 7L3
      • LMC Diabetes & Endocrinology (Barrie)
    • Brampton, Ontario, Canada, L6S 0C6
      • LMC ClinRsrh Inc.Brampton
    • Concord, Ontario, Canada, L4K 4M2
      • LMC Clin Res Inc. Thornhill
    • Etobicoke, Ontario, Canada, M9R 4E1
      • LMC Endo Ctr (Etobicoke) Ltd
    • Hamilton, Ontario, Canada, L8L 5G8
      • Wharton Med Clin Trials
    • Hamilton, Ontario, Canada, L8M 1K7
      • Premier Clinical Trial Research Network (PCTRN)
    • London, Ontario, Canada, N5W 6A2
      • Milestone Research
    • Nepean, Ontario, Canada, K2J 0V2
      • LMC Research Inc. Ottawa
    • Oakville, Ontario, Canada, L6M 1M1
      • LMC Clinical Research Inc. Oakville
    • Toronto, Ontario, Canada, M6G 1M2
      • Diabetes Heart Research Centre
    • Toronto, Ontario, Canada, M4G 3E8
      • Centricity Research LMC
    • Toronto, Ontario, Canada, M9V 4B4
      • Dr Anil K Gupta Med Prof Corp
    • Toronto, Ontario, Canada, M4P 1P2
      • Toronto Sleep Institute/MedSleep
  • Quebec
    • Mirabel, Quebec, Canada, J7J 2K8
      • Manna Research Mirabel
    • Montreal, Quebec, Canada, H4N 2W2
      • Centre Medical Acadie
    • Montreal, Quebec, Canada, QC H2L 4E9
      • Clinique Medicine Urbaine du Quartier Latin, Inc.
    • Saint-Laurent, Quebec, Canada, H4T 1Z9
      • LMC Clin Rsrch Inc. (Montreal)
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre de Recherche du CHUS
    • Terrebonne, Quebec, Canada, J6X 4P7
      • Ctr de méd métab de Lanaudière
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital Diabetes og Hormonsygdomme
  • Hvidovre, Denmark, 2650
    • Hvidovre Hospital Endokrinologisk forsknings afsnit 159
• Finland
  • Helsinki, Finland, 00014
    • Obesity Research Unit
  • Jyväskylä, Finland, 40620
    • StudyCor
• Spain
  • Madrid, Spain, 28009
    • Hospital Gregorio Maranon
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Seville, Spain, 41010
    • Hospital Infanta Luisa
• United Kingdom
  • Bradford-on-Avon, United Kingdom, BA15 1DQ
    • The Health Centre
  • Coventry, United Kingdom, CV2 2DX
    • University Hospital Coventry - WISDEM Centre
  • Exmouth, United Kingdom, EX8 2JF
    • Claremont Medical Practice
  • Harrow, United Kingdom, HA2 0RQ
    • GP Direct
  • London, United Kingdom, SE1 9RT
    • Guys Hospital
  • Soham, United Kingdom, CB7 5JD
    • The Staploe Medical Centre
  • Strensall, United Kingdom, YO32 5UA
    • MyHealth - Strensall Health Care Centre
  • South Yorkshire
    • Rotherham, South Yorkshire, United Kingdom, S65 1DA
      • Clifton Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female aged greater than or equal to 18 years at the time of signing informed consent.
• BMI greater than or equal to 30.0 kg/m^2

• Prediabetes defined as at least one of the following:

  • HbA1c between 6.0 and 6.4 percent (42 and 47 mmol/mol) (both inclusive) as measured by central laboratory at screening.
  • FPG between 5.5 and 6.9 mmol/L (99 and 125 mg/dL) (both inclusive) as measured by central laboratory at screening.

Exclusion Criteria:

• History of type 1 or type 2 diabetes.
• Treatment with glucose-lowering agent(s) within 90 days before screening.
• HbA1c greater than or equal to 6.5 percent (greater than or equal to 48 mmol/mol) as measured by central laboratory at screening.
• FPG greater than or equal to 7.0mmol/L (126 mg/dL) as measured by central laboratory at screening.

A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records.

• Treatment with any medication for the indication of obesity within the past 90 days before screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide; Participants will receive subcutaneus (s.c.) semaglutide 2.4 mg once weekly for 52 weeks	Drug: Semaglutide 2.4 mg; Administered subcutaneously (s.c., under the skin) once weekly as well as reduced-calorie diet and increased physical activity for 52 weeks. Doses gradually increased to 2.4 mg
Placebo Comparator: Placebo (semaglutide); Participants will receive subcutaneus (s.c.) placebo (semaglutide) once weekly for 52 weeks	Drug: Placebo; Administered subcutaneously once weekly (s.c., under the skin) as well as reduced-calorie diet and increased physical activity for 52 week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Weight (Percentage [%])	Change in body weight from randomisation (week 0) to end of treatment (week 52) is presented. The endpoint was evaluated based on the data from in-trial observation period which was defined as the time period where the participant was assessed in the main phase of the study. The 'in-trial' (main phase) observation period for a participant begins on the date of randomisation and ends at the first of the following dates (both inclusive): safety visit, withdrawal of consent, last contact with participant (for participants lost to follow-up), death.	From randomisation (week 0) to end of treatment (week 52)
Participants With Change to Normoglycemia	Number of participants in glycaemic categories, "normoglycaemia, pre-diabetes and type 2 diabetes" at Week 52 are presented. These categories were set as per the following criteria: 1) Normoglycaemia: glycosylated haemoglobin (HbA1c) lesser than (<) 6.0 percentage (%) and fasting plasma glucose (FPG) lesser than (<) 5.5 millimoles per liter (mmol/L). 2) Pre-diabetes: 6.0% lesser than or equal (≤) HbA1c lesser than (<) 6.5% or 5.5 mmol/L lesser than or equal (≤) FPG lesser than (<) 7.0 mmol/L or non-verified type 2 diabetes. 3) Type 2 diabetes: HbA1c greater than or equal (≥) 6.5% or FPG greater than or equal (≥) 7.0 mmol/L.	At week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Glycosylated Haemoglobin (HbA1c)	Change in glycosylated haemoglobin (HbA1c) from randomisation (week 0) to end of treatment (week 52) is presented. The endpoint was evaluated based on the data from in-trial observation period which was defined as the time period where the participant was assessed in the main phase of the study. The 'in-trial' (main phase) observation period for a participant begins on the date of randomisation and ends at the first of the following dates (both inclusive): safety visit, withdrawal of consent, last contact with participant (for participants lost to follow-up), death.	From randomisation (week 0) to end of treatment (week 52)
Change in Fasting Plasma Glucose (FPG)	Change in fasting plasma glucose (FPG) from randomisation (week 0) to end of treatment (week 52) is presented. The endpoint was evaluated based on the data from in-trial observation period which was defined as the time period where the participant was assessed in the main phase of the study. The 'in-trial' (main phase) observation period for a participant begins on the date of randomisation and ends at the first of the following dates (both inclusive): safety visit, withdrawal of consent, last contact with participant (for participants lost to follow-up), death.	From randomisation (week 0) to end of treatment (week 52)
Change in Waist Circumference	Change in waist circumference from randomisation (week 0) to end of treatment (week 52) is presented. The endpoint was evaluated based on the data from in-trial observation period which was defined as the time period where the participant was assessed in the main phase of the study. The 'in-trial' (main phase) observation period for a participant begins on the date of randomisation and ends at the first of the following dates (both inclusive): safety visit, withdrawal of consent, last contact with participant (for participants lost to follow-up), death.	From randomisation (week 0) to end of treatment (week 52)
Change in Systolic Blood Pressure	Change in systolic blood pressure from randomisation (week 0) to end of treatment (week 52) is presented. The endpoint was evaluated based on the data from in-trial observation period which was defined as the time period where the participant was assessed in the main phase of the study. The 'in-trial' (main phase) observation period for a participant begins on the date of randomisation and ends at the first of the following dates (both inclusive): safety visit, withdrawal of consent, last contact with participant (for participants lost to follow-up), death.	From randomisation (week 0) to end of treatment (week 52)
Change in Triglycerides (Millimoles Per Liter [mmol/L]) - Ratio to Baseline	Change in triglycerides (measured in mmol/L) from randomisation (week 0) to end of treatment (week 52) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period which was defined as the time period where the participant was assessed in the main phase of the study. The 'in-trial' (main phase) observation period for a participant begins on the date of randomisation and ends at the first of the following dates (both inclusive): safety visit, withdrawal of consent, last contact with participant (for participants lost to follow-up), death.	From randomisation (week 0) to end of treatment (week 52)
Change in Total Cholesterol (mmol/L) - Ratio to Baseline	Change in total cholesterol (measured in mmol/L) from randomisation (week 0) to end of treatment (week 52) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period which was defined as the time period where the participant was assessed in the main phase of the study. The 'in-trial' (main phase) observation period for a participant begins on the date of randomisation and ends at the first of the following dates (both inclusive): safety visit, withdrawal of consent, last contact with participant (for participants lost to follow-up), death.	From randomisation (week 0) to end of treatment (week 52)
Change in High Density Lipoprotein (HDL) Cholesterol (mmol/L) - Ratio to Baseline	Change in high density lipoprotein (HDL) cholesterol (measured in mmol/L) from randomisation (week 0) to end of treatment (week 52) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period which was defined as the time period where the participant was assessed in the main phase of the study. The 'in-trial' (main phase) observation period for a participant begins on the date of randomisation and ends at the first of the following dates (both inclusive): safety visit, withdrawal of consent, last contact with participant (for participants lost to follow-up), death.	From randomisation (week 0) to end of treatment (week 52)
Change in Low Density Lipoprotein (LDL) Cholesterol (mmol/L) - Ratio to Baseline	Change in low density lipoprotein (LDL) cholesterol (measured in mmol/L) from randomisation (week 0) to end of treatment (week 52) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period which was defined as the time period where the participant was assessed in the main phase of the study. The 'in-trial' (main phase) observation period for a participant begins on the date of randomisation and ends at the first of the following dates (both inclusive): safety visit, withdrawal of consent, last contact with participant (for participants lost to follow-up), death.	From randomisation (week 0) to end of treatment (week 52)
Change in Very Low Density Lipoprotein (VLDL) Cholesterol (mmol/L) - Ratio to Baseline	Change in very low density lipoprotein (VLDL) cholesterol (measured in mmol/L) from randomisation (week 0) to end of treatment (week 52) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period which was defined as the time period where the participant was assessed in the main phase of the study. The 'in-trial' (main phase) observation period for a participant begins on the date of randomisation and ends at the first of the following dates (both inclusive): safety visit, withdrawal of consent, last contact with participant (for participants lost to follow-up), death.	From randomisation (week 0) to end of treatment (week 52)
Change in Body Weight (Kilogram [Kg])	Change in body weight from randomisation (week 0) to end of treatment (week 52) is presented. The endpoint was evaluated based on the data from in-trial observation period which was defined as the time period where the participant was assessed in the main phase of the study. The 'in-trial' (main phase) observation period for a participant begins on the date of randomisation and ends at the first of the following dates (both inclusive): safety visit, withdrawal of consent, last contact with participant (for participants lost to follow-up), death.	From randomisation (week 0) to week 52
Participants Achieving Body Weight Reduction Greater Than or Equal (≥) 5% (Yes/No)	Participants who achieved body weight reduction greater than or equal to 5% (Yes/No) at week 52 is presented. The endpoint was evaluated based on the data from in-trial observation period which was defined as the time period where the participant was assessed in the main phase of the study. The 'in-trial' (main phase) observation period for a participant begins on the date of randomisation and ends at the first of the following dates (both inclusive): safety visit, withdrawal of consent, last contact with participant (for participants lost to follow-up), death.	At week 52
Participants Achieving Body Weight Reduction Greater Than or Equal (≥) 10% (Yes/No)	Participants who achieved body weight reduction greater than or equal to 10% (Yes/No) at week 52 is presented. The endpoint was evaluated based on the data from in-trial observation period which was defined as the time period where the participant was assessed in the main phase of the study. The 'in-trial' (main phase) observation period for a participant begins on the date of randomisation and ends at the first of the following dates (both inclusive): safety visit, withdrawal of consent, last contact with participant (for participants lost to follow-up), death.	At week 52
Participants Achieving Body Weight Reduction Greater Than or Equal (≥) 15% (Yes/No)	Participants who achieved body weight reduction greater than or equal to 15% (Yes/No) at week 52 is presented. The endpoint was evaluated based on the data from in-trial observation period which was defined as the time period where the participant was assessed in the main phase of the study. The 'in-trial' (main phase) observation period for a participant begins on the date of randomisation and ends at the first of the following dates (both inclusive): safety visit, withdrawal of consent, last contact with participant (for participants lost to follow-up), death.	At week 52
Participants Achieving Body Weight Reduction Greater Than or Equal (≥) 20% (Yes/No)	Participants who achieved body weight reduction greater than or equal to 20% (Yes/No) at week 52 is presented. The endpoint was evaluated based on the data from in-trial observation period which was defined as the time period where the participant was assessed in the main phase of the study. The 'in-trial' (main phase) observation period for a participant begins on the date of randomisation and ends at the first of the following dates (both inclusive): safety visit, withdrawal of consent, last contact with participant (for participants lost to follow-up), death.	At week 52
Change in Pulse	Change in pulse from randomisation (week 0) to end of treatment (week 52) is presented. The endpoint was evaluated based on the data from in-trial observation period which was defined as the time period where the participant was assessed in the main phase of the study. The 'in-trial' (main phase) observation period for a participant begins on the date of randomisation and ends at the first of the following dates (both inclusive): safety visit, withdrawal of consent, last contact with participant (for participants lost to follow-up), death.	From randomisation (week 0) to end of treatment (week 52)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 1452), Novo Nordisk A/S

Publications and helpful links

General Publications

• McGowan BM, Bruun JM, Capehorn M, Pedersen SD, Pietilainen KH, Muniraju HAK, Quiroga M, Varbo A, Lau DCW; STEP 10 Study Group. Efficacy and safety of once-weekly semaglutide 2.4 mg versus placebo in people with obesity and prediabetes (STEP 10): a randomised, double-blind, placebo-controlled, multicentre phase 3 trial. Lancet Diabetes Endocrinol. 2024 Sep;12(9):631-642. doi: 10.1016/S2213-8587(24)00182-7. Epub 2024 Jul 29.

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2021
• Primary Completion (Actual): January 6, 2023
• Study Completion (Actual): July 14, 2023

Study Registration Dates

• First Submitted: September 2, 2021
• First Submitted That Met QC Criteria: September 2, 2021
• First Posted (Actual): September 10, 2021

Study Record Updates

• Last Update Posted (Actual): January 29, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; semaglutide
• Other Study ID Numbers: NN9536-4734; U1111-1253-1956 (Other Identifier: World Health Organization (WHO)); 2020-002939-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: "According to the Novo Nordisk disclosure commitment on novonordisk-trials.com"

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No