Tirzepatide activates two gut-hormone receptors, GIP and GLP-1. It is sold as Mounjaro (type 2 diabetes) and Zepbound (weight management and other approved uses), as a once-weekly injection.
What the studies found10 studies explained
SURMOUNT-1 tested tirzepatide for obesity; SURMOUNT-5 compared it head to head with semaglutide; SURPASS-2 did the same in type 2 diabetes. Further trials covered sleep apnea and heart failure with preserved ejection fraction.
Jastreboff AM, Aronne LJ, Ahmad NN · N Engl J Med · 2022 · PMID 35658024
humanRandomized, double-blind, placebo-controlled phase 3 (SURMOUNT-1)
- Who / how many
- 2,539 adults with obesity, no diabetes
- What they found
- At 72 weeks mean weight change was -15.0%, -19.5% and -20.9% on 5, 10 and 15 mg vs -3.1% with placebo.
- Limitations
- Manufacturer-funded; participants were not diabetic, so results differ for people with type 2 diabetes.
Frías JP, Davies MJ, Rosenstock J · N Engl J Med · 2021 · PMID 34170647
humanOpen-label randomized phase 3 (SURPASS-2)
- Who / how many
- 1,879 adults with type 2 diabetes
- What they found
- HbA1c fell more with tirzepatide at all doses than with semaglutide 1 mg (e.g. -2.30 vs -1.86 points at 15 mg), with greater weight loss.
- Limitations
- Open-label, 40 weeks, and semaglutide was compared at 1 mg rather than the highest available doses.
Aronne LJ, Horn DB, le Roux CW · N Engl J Med · 2025 · PMID 40353578
humanOpen-label phase 3b head-to-head (SURMOUNT-5)
- Who / how many
- 751 adults with obesity, no diabetes
- What they found
- Tirzepatide -20.2% vs semaglutide -13.7% weight change at 72 weeks.
- Limitations
- Open-label and funded by the maker of tirzepatide.
Jastreboff AM, le Roux CW, Stefanski A · N Engl J Med · 2025 · PMID 39536238
humanRandomized, double-blind, placebo-controlled phase 3 (SURMOUNT-1, 3-year analysis)
- Who / how many
- 1,032 participants with obesity and prediabetes (from 2,539 total)
- What they found
- Over 176 weeks, weight fell by 12.3% with 5 mg and 18.7% with 10 mg, and tirzepatide markedly lowered the risk of progression to type 2 diabetes. No new safety signals were identified; most adverse events were gastrointestinal.
- Limitations
- Manufacturer-funded and restricted to people with prediabetes.
Aronne LJ, Sattar N, Horn DB · JAMA · 2024 · PMID 38078870
humanRandomized withdrawal trial (SURMOUNT-4)
- Who / how many
- 670 adults randomized after a 36-week tirzepatide lead-in
- What they found
- People who continued tirzepatide kept losing weight (overall -25.3% from baseline at week 88) while those switched to placebo regained much of it (-9.9% overall).
- Limitations
- Funded by Eli Lilly. The lead-in was open-label, and only people who tolerated the drug were randomized.
Garvey WT, Frias JP, Jastreboff AM · Lancet · 2023 · PMID 37385275
humanRandomized, double-blind, placebo-controlled phase 3 (SURMOUNT-2)
- Who / how many
- Adults with obesity and type 2 diabetes
- What they found
- Tirzepatide 10 mg and 15 mg produced substantial, clinically meaningful weight reduction over 72 weeks with a safety profile similar to other incretin-based weight drugs.
- Limitations
- Funded by Eli Lilly. Two deaths occurred in the 10 mg group; investigators judged them unrelated to treatment.
Malhotra A, Grunstein RR, Fietze I · N Engl J Med · 2024 · PMID 38912654
humanTwo randomized, double-blind phase 3 trials (SURMOUNT-OSA)
- Who / how many
- Adults with moderate-to-severe obstructive sleep apnea and obesity, with and without CPAP
- What they found
- Over 52 weeks, tirzepatide reduced the apnea-hypopnea index, body weight, hypoxic burden, hsCRP and systolic blood pressure, and improved sleep-related outcomes versus placebo.
- Limitations
- Funded by Eli Lilly. Benefit is tied to weight loss, and 52 weeks is short for a chronic condition.
Packer M, Zile MR, Kramer CM · N Engl J Med · 2025 · PMID 39555826
humanRandomized, double-blind, placebo-controlled trial (SUMMIT)
- Who / how many
- 731 adults with heart failure with preserved ejection fraction and obesity
- What they found
- Tirzepatide lowered the risk of cardiovascular death or a worsening heart-failure event compared with placebo and improved quality of life. Adverse events leading to discontinuation were more common with tirzepatide (6.3% vs 1.4%).
- Limitations
- Funded by Eli Lilly, relatively few outcome events, and limited to this specific population.
Nicholls SJ, Pavo I, Bhatt DL · N Engl J Med · 2025 · PMID 41406444
humanActive-comparator, double-blind noninferiority trial (SURPASS-CVOT)
- Who / how many
- 13,299 adults with type 2 diabetes and atherosclerotic cardiovascular disease
- What they found
- Tirzepatide was noninferior to dulaglutide for a composite of cardiovascular death, heart attack or stroke (superiority was not shown, P = 0.09). More gastrointestinal adverse events occurred with tirzepatide.
- Limitations
- Compared against dulaglutide, not placebo, so it shows safety relative to another drug rather than absolute benefit. Funded by Eli Lilly.
Zeng Q, Xu J, Mu X · Front Endocrinol (Lausanne) · 2023 · PMID 37908750
reviewSystematic review and meta-analysis of safety
- Who / how many
- 9 randomized trials, 9,871 participants
- What they found
- No increased pancreatitis risk was found. The composite of gallbladder or biliary disease was higher with tirzepatide versus placebo or basal insulin (relative risk 1.97), though individual outcomes such as cholelithiasis were not significantly increased.
- Limitations
- Pooled trials are short, and rare events are hard to detect. The authors say the gallbladder signal warrants attention.
More published research (summaries coming)
- Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight. (Diabetes Obes Metab, 2025)
- Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials. (Diabetologia, 2024)
- Tirzepatide for Weight Reduction in Chinese Adults With Obesity: The SURMOUNT-CN Randomized Clinical Trial. (JAMA, 2024)
- Weight Loss Efficacy of Tirzepatide Compared to Placebo or GLP-1 Receptor Agonists in Adults With Obesity or Overweight: A Meta-Analysis of Randomized Controlled Trials With ≥ 20 Weeks Treatment Duration. (J Obes, 2025)
- Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis. (N Engl J Med, 2024)
- Effect of tirzepatide on glycaemic control and weight loss compared with other glucagon-like peptide-1 receptor agonists in Japanese patients with type 2 diabetes mellitus. (Diabetes Obes Metab, 2024)
- Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. (Lancet, 2021)
- Tirzepatide Versus Semaglutide on Weight Loss in Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis of Direct Comparative Studies. (Endocrinol Diabetes Metab, 2025)
Gastrointestinal events were most common and mostly mild to moderate, mainly during dose escalation. In SURMOUNT-1, treatment discontinuation due to adverse events ranged from 4.3% to 7.1% across tirzepatide arms vs 2.6% on placebo.
