Efficacy and Safety of Tirzepatide Once Weekly Versus Placebo in Participants Who Are Either Obese or Overweight With Weight-Related Comorbidities (SURMOUNT-1) (SURMOUNT-1)

Efficacy and Safety of Tirzepatide Once Weekly in Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight With Weight-Related Comorbidities: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-1)

This Phase 3 study evaluates the efficacy and safety of once-weekly subcutaneous tirzepatide (a dual GIP and GLP-1 receptor agonist) at 5 mg, 10 mg, or 15 mg versus placebo, each used with a reduced-calorie diet and increased physical activity, in adults without type 2 diabetes who have obesity or are overweight with weight-related comorbidities. The primary efficacy assessment is at Week 72. Participants with prediabetes at randomization may continue in an additional long-term treatment period to assess progression to type 2 diabetes and longer-term weight outcomes.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Overweight (Without Type 2 Diabetes) With Weight-related Comorbidities
• Intervention / Treatment: Drug: Tirzepatide; Drug: Placebo; Behavioral: Reduced-calorie diet

Detailed Description

After screening, eligible participants are randomized in a 1:1:1:1 ratio to receive tirzepatide 5 mg, 10 mg, 15 mg, or placebo once weekly by subcutaneous injection using an autoinjector. All participants receive lifestyle counseling focused on a reduced-calorie diet and increased physical activity. The main treatment period is 72 weeks. Participants identified with prediabetes at randomization can continue study treatment for up to 176 weeks (plus follow-up), allowing evaluation of longer-term weight management and time to onset/progression to type 2 diabetes. Safety is monitored throughout, including adverse events and laboratory testing.

• Study Type: Interventional
• Enrollment (Estimated): 2539
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Seni S Lu, Phd; Phone Number: +86 13076790030; Email: Seni-Lu@beijing-biotech.com

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518036
      • Recruiting
      • Peking University Shenzhen Hospital
      • Contact: Zhen J Peng, Phd; Phone Number: +86 13076790039; Email: Zhen-Peng@beijing-biotech.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• BMI ≥30 kg/m², OR BMI ≥27 kg/m² with ≥1 weight-related comorbidity (e.g., hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease)
• History of at least one unsuccessful dietary effort to lose weight (self-reported)
• Investigator judges participant capable and willing to self-inject (or have assistance), follow lifestyle advice, maintain a diary, and complete questionnaires
• Age ≥18 years
• Meets protocol contraception/pregnancy criteria (as applicable) and provides written informed consent

Exclusion Criteria:

• Type 1 or type 2 diabetes, history of ketoacidosis/hyperosmolar state, or screening labs diagnostic of diabetes
• Recent significant weight change (>5 kg within 3 months prior to screening)
• Prior/planned bariatric surgery; recent/ongoing endoscopic or device-based obesity therapies
• Severe renal impairment (eGFR <30 mL/min/1.73 m²)
• Clinically significant gastric emptying abnormality or chronic use of drugs that directly affect GI motility
• History of chronic or acute pancreatitis
• Clinically significant thyroid abnormalities at screening (e.g., TSH outside protocol range) or anticipated need to initiate thyroid replacement during study
• Obesity due to other endocrinologic disorders (e.g., Cushing syndrome) or monogenic/syndromic obesity (e.g., MC4R deficiency, Prader-Willi syndrome)
• Significant unstable major depressive disorder/severe psychiatric disorder, lifetime suicide attempt, or concerning suicidality screening (PHQ-9/C-SSRS criteria)
• Uncontrolled hypertension; recent major cardiovascular events; NYHA class IV heart failure
• Active or significant liver disease or certain elevated liver tests at screening (per protocol thresholds)
• Elevated calcitonin above protocol thresholds; personal/family history of medullary thyroid carcinoma or MEN2
• Active/untreated malignancy or remission <5 years (with specified exceptions)
• Any other condition contraindicating GLP-1 receptor agonist therapy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Tirzepatide 5 mg once weekly + lifestyle intervention	Drug: Tirzepatide; (once-weekly SC injection; doses 5/10/15 mg); Drug: Placebo; (once-weekly SC injection); Behavioral: Reduced-calorie diet; increased physical activity counseling
Experimental: Arm 2: Tirzepatide 10 mg once weekly + lifestyle intervention	Drug: Tirzepatide; (once-weekly SC injection; doses 5/10/15 mg); Drug: Placebo; (once-weekly SC injection); Behavioral: Reduced-calorie diet; increased physical activity counseling
Experimental: Arm 3: Tirzepatide 15 mg once weekly + lifestyle intervention	Drug: Tirzepatide; (once-weekly SC injection; doses 5/10/15 mg); Drug: Placebo; (once-weekly SC injection); Behavioral: Reduced-calorie diet; increased physical activity counseling
Experimental: Arm 4: Placebo once weekly + lifestyle intervention	Drug: Tirzepatide; (once-weekly SC injection; doses 5/10/15 mg); Drug: Placebo; (once-weekly SC injection); Behavioral: Reduced-calorie diet; increased physical activity counseling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean percent change in body weight from randomization	72 Weeks
Percentage of participants achieving ≥5% body weight reduction from randomization	72 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in body weight	Mean change in body weight (kg) from randomization (pooled 10 mg and 15mg vs placebo)	72 Weeks
Changes in cardiometabolic measures in triglycerides		72 weeks

Collaborators and Investigators

• Sponsor: Hudson Biotech

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2026
• Primary Completion (Estimated): February 14, 2027
• Study Completion (Estimated): March 17, 2028

Study Registration Dates

• First Submitted: March 8, 2026
• First Submitted That Met QC Criteria: March 14, 2026
• First Posted (Actual): March 19, 2026

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 14, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: GLP-1; obesity; overweight; placebo; subcutaneous; weight management; lifestyle intervention; randomized; double-blind; GIP; Tirzepatide; LY3298176; dual incretin; once-weekly
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide
• Other Study ID Numbers: I8F-MC-GPHK(b)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No