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

NCT07481747 | Recruiting Phase 3 DMC

• 1 other identifier: I8F-MC-GPHK(b)
• Study Type: interventional
• Target: 2,539
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Obesity; Overweight (Without Type 2 Diabetes) With Weight-related Comorbidities

Keywords

Tirzepatide; LY3298176; dual incretin; GIP; GLP-1; obesity; overweight; weight management; placebo; randomized; double-blind; once-weekly; subcutaneous; lifestyle intervention

Outcome Measures

Primary Outcomes (2)

• Mean percent change in body weight from randomization

  72 Weeks

• Percentage of participants achieving ≥5% body weight reduction from randomization

  72 Weeks

Secondary Outcomes (2)

• Mean change in body weight

  72 Weeks

• Changes in cardiometabolic measures in triglycerides

  72 weeks

Study Arms (4)

Arm 1: Tirzepatide 5 mg once weekly + lifestyle intervention

EXPERIMENTAL

Drug: Tirzepatide; Drug: Placebo; Behavioral: Reduced-calorie diet

Arm 2: Tirzepatide 10 mg once weekly + lifestyle intervention

EXPERIMENTAL

Drug: Tirzepatide; Drug: Placebo; Behavioral: Reduced-calorie diet

Arm 3: Tirzepatide 15 mg once weekly + lifestyle intervention

EXPERIMENTAL

Drug: Tirzepatide; Drug: Placebo; Behavioral: Reduced-calorie diet

Arm 4: Placebo once weekly + lifestyle intervention

EXPERIMENTAL

Drug: Tirzepatide; Drug: Placebo; Behavioral: Reduced-calorie diet

Interventions

Tirzepatide DRUG

(once-weekly SC injection; doses 5/10/15 mg)

Arm 1: Tirzepatide 5 mg once weekly + lifestyle intervention; Arm 2: Tirzepatide 10 mg once weekly + lifestyle intervention; Arm 3: Tirzepatide 15 mg once weekly + lifestyle intervention; Arm 4: Placebo once weekly + lifestyle intervention

Placebo DRUG

(once-weekly SC injection)

Arm 1: Tirzepatide 5 mg once weekly + lifestyle intervention; Arm 2: Tirzepatide 10 mg once weekly + lifestyle intervention; Arm 3: Tirzepatide 15 mg once weekly + lifestyle intervention; Arm 4: Placebo once weekly + lifestyle intervention

Reduced-calorie diet BEHAVIORAL

increased physical activity counseling

Arm 1: Tirzepatide 5 mg once weekly + lifestyle intervention; Arm 2: Tirzepatide 10 mg once weekly + lifestyle intervention; Arm 3: Tirzepatide 15 mg once weekly + lifestyle intervention; Arm 4: Placebo once weekly + lifestyle intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hudson Biotech: lead

Study Sites (1)

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

Obesity; Overweight

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Central Study Contacts

Seni S Lu, Phd

CONTACT

+86 13076790030; Seni-Lu@beijing-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants and investigators are blinded to treatment assignment. Study drug and placebo are administered using similar autoinjector pens; randomization and drug dispensing are managed centrally via an interactive system.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Parallel group, 4-arm study. Participants randomized 1:1:1:1 to tirzepatide 5 mg, 10 mg, 15 mg, or placebo once weekly, plus lifestyle intervention. Main evaluation at 72 weeks; participants with prediabetes may continue treatment up to 176 weeks.

Study Record Dates

• First Submitted: March 8, 2026
• First Posted: March 19, 2026
• Study Start: February 2, 2026
• Primary Completion (Estimated): February 14, 2027
• Study Completion (Estimated): March 17, 2028
• Last Updated: March 19, 2026

Record last verified: 2026-03

Locations

CN (1)