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Tir7.8
Tirzepatide Research
Mostly mechanism / observationalLimited safety
12 peer-reviewed studies
What the evidence says
Mostly mechanism / observational
Most Tirzepatide studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 2021–2025 with a typical study size of 1,437 participants.
Based on 12 studies · 2 meta-analyses · 10 RCTs · 69,784 total participants
Confidence
High
By outcome
Weight management
Mostly mechanism / observational10 studies
Safety profile
Mostly mechanism / observational9 studies
Glycemic & metabolic control
Mostly mechanism / observational7 studies
Heart & blood pressure
Too few graded studies2 studies
Sleep apnea & respiratory
Too few graded studies1 study
Active research area
12 studies in the last 5 years · Latest meta-analysis: 2024
20212025
1RCTn=2,539 · very large study2022
The mean percentage change in weight at week 72 was -15.0%... -19.5%... and -20.9%... and -3.1% with placebo.
Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. · N Engl J Med (2022)
72-week phase-3 double-blind RCT (SURMOUNT-1) in 2539 adults with obesity (without diabetes), tirzepatide 5/10/15 mg vs placebo
Mean weight change -15.0%, -19.5%, -20.9% vs -3.1% placebo — among the largest weight loss seen with a pharmacotherapy
50-57% of participants on 10/15 mg lost ≥20% of body weight vs 3% on placebo
The least-squares mean percent change in weight at week 72 was -20.2%... with tirzepatide and -13.7%... with semaglutide (P<0.001).
Aronne LJ, Horn DB, le Roux CW, Ho W, Falcon BL, Gomez Valderas E, Das S, Lee CJ, Glass LC, Senyucel C, Dunn JP; SURMOUNT-5 Trial Investigators. · N Engl J Med (2025)
Phase-3b open-label head-to-head RCT (SURMOUNT-5) in 751 adults with obesity but without diabetes, max-tolerated tirzepatide vs max-tolerated semaglutide
Weight loss -20.2% with tirzepatide vs -13.7% with semaglutide at 72 weeks — tirzepatide superior
Greater waist-circumference reduction with tirzepatide (-18.4 vs -13.0 cm)
Among persons with moderate-to-severe obstructive sleep apnea and obesity, tirzepatide reduced the AHI, body weight, hypoxic burden, hsCRP concentration, and systolic blood pressure.
Malhotra A, Grunstein RR, Fietze I, Weaver TE, Redline S, Azarbarzin A, Sands SA, Schwab RJ, Dunn JP, Chakladar S, Bunck MC, Bednarik J; SURMOUNT-OSA Investigators. · N Engl J Med (2024)
Two 52-week phase-3 double-blind RCTs (SURMOUNT-OSA) in obese adults with moderate-to-severe OSA, off and on PAP therapy
Apnea-hypopnea index fell by an estimated 20.0 events/hour (trial 1) and 23.8 events/hour (trial 2) more than placebo
Also improved body weight, hypoxic burden, hsCRP, and systolic blood pressure
Tirzepatide treatment was not associated with excess cardiovascular risk.
Del Prato S, Kahn SE, Pavo I, Weerakkody GJ, Yang Z, Doupis J, Aizenberg D, Wynne AG, Riesmeyer JS, Heine RJ, Wiese RJ; SURPASS-4 Investigators. · Lancet (2021)
Phase-3 open-label RCT (SURPASS-4) in 1995 adults with type 2 diabetes and high cardiovascular risk, tirzepatide 5/10/15 mg vs titrated insulin glargine
HbA1c reductions of -2.43% (10 mg) and -2.58% (15 mg) vs -1.44% glargine
Adjudicated MACE not increased on tirzepatide (HR 0.74, 95% CI 0.51-1.08); lower hypoglycemia than glargine
Tirzepatide (5, 10, and 15 mg) was superior to titrated insulin degludec, with greater reductions in HbA1c and bodyweight at week 52 and a lower risk of hypoglycaemia.
Ludvik B, Giorgino F, Jódar E, Frias JP, Fernández Landó L, Brown K, Bray R, Rodríguez Á. · Lancet (2021)
52-week phase-3 open-label RCT (SURPASS-3) in 1437 adults with type 2 diabetes, tirzepatide vs titrated insulin degludec
HbA1c reductions of 1.93-2.37% vs 1.34% degludec; estimated treatment difference -0.59% to -1.04%
Tirzepatide reduced bodyweight (-7.5 to -12.9 kg) while degludec increased it (+2.3 kg)
The addition of subcutaneous tirzepatide, compared with placebo, to titrated insulin glargine resulted in statistically significant improvements in glycemic control after 40 weeks.
Tirzepatide 15 mg had the highest efficacy compared with placebo for achieving ≥15% weight loss (risk ratio 10.24, 95% CI: 6.42-16.34).
Pan XH, Tan B, Chin YH, Lee ECZ, Kong G, Chong B, Kueh M, Khoo CM, Mehta A, Majety P, Grandhi GR, Dimitriadis GK, Foo R, Chew NWS, Le Roux CW, Mamas MA, Chan MY. · Obesity (Silver Spring) (2024)
Network meta-analysis of 31 RCTs (>35,000 patients) comparing tirzepatide, GLP-1 RAs, and other FDA-approved weight-loss drugs
Tirzepatide 15 mg ranked in the top three across weight, glycemic, lipid, and blood-pressure parameters
Highest efficacy for ≥15% weight loss vs placebo (RR 10.24)