Efficacy and Safety of Tirzepatide Once Weekly Versus Placebo in Participants Who Are Either Obese or Overweight With Weight-Related Comorbidities (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)
Hudson Biotech
2,539 participants
Feb 2, 2026
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria5
- 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 Criteria14
- 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
Interventions
(once-weekly SC injection)
(once-weekly SC injection; doses 5/10/15 mg)
increased physical activity counseling
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT07481747