Semaglutides
Trial evidence

Tirzepatide Clinical Trial Results: What the Studies Show

In phase 3 trials, tirzepatide produced 15.0–20.9% mean weight loss over 72 weeks in adults with obesity (vs 3.1% on placebo) and cut HbA1c by 1.87–2.8 points across the diabetes trials, beating semaglutide 1 mg and two insulins head to head. Heart, kidney, and liver trial results were not verified for this page.

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Tirzepatide (Mounjaro, Zepbound) has been tested in two phase 3 programs: SURPASS, the type 2 diabetes trials [1, 2, 3, 4, 5], and SURMOUNT, the obesity and weight trials [6, 7, 8]. Across those trials, adults with obesity but without diabetes lost an average of 15.0% to 20.9% of their body weight over 72 weeks, compared with 3.1% on placebo [6]. Adults who also had type 2 diabetes lost 12.8% to 14.7% [7]. In the diabetes trials, HbA1c fell between 1.87 and 2.8 percentage points depending on the trial and dose [1, 2, 3, 4, 5], and tirzepatide beat semaglutide 1 mg, insulin degludec, insulin glargine, and dulaglutide in head-to-head comparisons [2, 3, 4, 5].

Trials in heart failure, liver disease, sleep apnea, and other conditions also exist, but their results were not verified for this page and are not reported here. The kidney analyses that have been published are post hoc or exploratory rather than dedicated outcome trials [18, 19, 20].

A note on coverage: for several trials named below, only the publication title was available when this page was prepared. Those trials are described with what their titles support, and their results are not reported here.

Tirzepatide is a dual GIP and GLP-1 receptor agonist, meaning it acts on two gut-hormone receptors rather than one [1, 2, 5]. Semaglutide, by contrast, is a selective GLP-1 receptor agonist [2]. The first phase 3 tirzepatide publications appeared in 2021 [1, 2, 3]. SURPASS-1, -2, -3, SURPASS J-mono, and SURMOUNT-1 and -2 were funded by Eli Lilly and Company, and several authors on those papers are Lilly employees and shareholders [1, 2, 3, 4, 6, 7].

How much weight did people lose in the main obesity trial?

SURMOUNT-1 enrolled 2,539 adults with a body-mass index (BMI) of 30 or higher, or 27 or higher with at least one weight-related complication; people with diabetes were excluded [6]. It ran 72 weeks, was double-blind and placebo-controlled, and included a 20-week dose-escalation period [6]. At baseline, participants weighed 104.8 kg on average with a mean BMI of 38.0, and 94.5% had a BMI of 30 or higher [6].

At week 72, mean weight change was -15.0% on the 5 mg dose, -19.5% on 10 mg, and -20.9% on 15 mg, versus -3.1% on placebo [6].

SURMOUNT-1, week 725 mg10 mg15 mgPlacebo
Mean weight change-15.0%-19.5%-20.9%-3.1%
Lost 5% or more85%89%91%35%
Lost 20% or morenot reported separately50%57%3%
Quit drug due to side effects4.3%7.1%6.2%2.6%

All figures are from the primary publication [6]. The most common side effects were gastrointestinal, mostly mild to moderate, and occurred mainly during dose escalation [6]. The trial is registered as NCT04184622 [6].

What happened in people who also had type 2 diabetes?

SURMOUNT-2 tested tirzepatide in 938 adults across seven countries with BMI of 27 or higher and HbA1c between 7% and 10% [7]. Baseline averages were 100.7 kg, BMI 36.1, and HbA1c 8.02% [7]. Over 72 weeks, weight fell 12.8% on the 10 mg dose and 14.7% on 15 mg, versus 3.2% on placebo, giving treatment differences of -9.6 and -11.6 percentage points [7]. Between 79% and 83% of tirzepatide users lost at least 5% of body weight, versus 32% on placebo [7].

The weight loss was smaller than in SURMOUNT-1, where participants did not have diabetes. The two trials enrolled different populations — SURMOUNT-1 excluded diabetes, while SURMOUNT-2 required it — so the figures describe each population separately rather than a controlled comparison [6, 7]. Serious adverse events were reported by 7% of participants overall, and two deaths occurred in the 10 mg group, which the investigator judged unrelated to treatment [7].

SURMOUNT-3 used a different design: tirzepatide was started only after an intensive lifestyle intervention in adults with overweight or obesity [8].

Did tirzepatide beat semaglutide head to head?

Yes, but at the 1 mg diabetes dose of semaglutide, not the higher obesity dose. SURPASS-2 was an open-label, 40-week trial in 1,879 patients with type 2 diabetes, comparing tirzepatide 5, 10, and 15 mg against semaglutide 1 mg [2]. Baseline HbA1c was 8.28%, mean age 56.6 years, and mean weight 93.7 kg [2].

HbA1c fell 2.01, 2.24, and 2.30 percentage points on tirzepatide 5, 10, and 15 mg, versus 1.86 points on semaglutide 1 mg [2]. The differences versus semaglutide were -0.15 points (95% CI -0.28 to -0.03; P=0.02), -0.39 points (-0.51 to -0.26), and -0.45 points (-0.57 to -0.32) [2]. Weight differences favored tirzepatide by 1.9 kg, 3.6 kg, and 5.5 kg [2]. Serious adverse events were reported in 5% to 7% of tirzepatide patients versus 3% on semaglutide [2].

SURMOUNT-5 later ran tirzepatide head to head against semaglutide specifically for obesity [9]. No published trial has compared tirzepatide against semaglutide 7.2 mg [9].

How much did tirzepatide lower blood sugar versus placebo?

SURPASS-1 tested tirzepatide as monotherapy in 478 patients over 40 weeks at 52 centers in India, Japan, Mexico, and the USA; participants were inadequately controlled on diet and exercise and naive to injectable diabetes therapy [1]. From a baseline HbA1c of 7.9%, levels fell 1.87, 1.89, and 2.07 points on the three tirzepatide doses, versus a rise of 0.04 points on placebo [1]. Between 31% and 52% of tirzepatide users reached HbA1c below 5.7%, versus 1% on placebo, and 87% to 92% reached below 7.0%, versus 20% [1]. Weight fell 7.0 to 9.5 kg, and no clinically significant or severe hypoglycemia occurred on tirzepatide [1].

How did tirzepatide compare with insulin?

SURPASS-3 compared tirzepatide with titrated insulin degludec over 52 weeks in 1,444 patients on metformin with or without an SGLT2 inhibitor [3]. HbA1c fell 1.93, 2.20, and 2.37 points on tirzepatide versus 1.34 on degludec; 82% to 93% reached HbA1c below 7.0% versus 61% on insulin [3]. Weight fell 7.5 to 12.9 kg on tirzepatide while degludec added 2.3 kg [3]. Hypoglycemia (below 54 mg/dL or severe) occurred in 1%, 1%, and 2% of the tirzepatide groups versus 7% on degludec [3].

SURPASS-4 compared tirzepatide with insulin glargine, and a post-hoc analysis of that trial examined kidney outcomes [18].

What did trials outside the United States show?

SURPASS J-mono ran at 46 centers in Japan, enrolling 636 patients over 52 weeks against dulaglutide 0.75 mg [4]. HbA1c fell 2.4, 2.6, and 2.8 points on tirzepatide versus 1.3 on dulaglutide, with treatment differences of 1.1 to 1.5 points [4]. Weight fell 5.8 kg (-7.8%), 8.5 kg (-11.0%), and 10.7 kg (-13.9%) on tirzepatide versus 0.5 kg (-0.7%) on dulaglutide [4].

SURPASS-AP-Combo enrolled 917 patients, 763 of them in China, at 66 hospitals in China, South Korea, Australia, and India, comparing tirzepatide with daily insulin glargine over 40 weeks [5]. HbA1c fell 2.24, 2.44, and 2.49 points on tirzepatide versus 0.95 on glargine; 75.4%, 86.0%, and 84.4% reached HbA1c below 7.0% versus 23.7% on insulin [5]. Weight fell 5.0, 7.0, and 7.2 kg on tirzepatide while glargine added 1.5 kg, and no severe hypoglycemia was reported [5].

What about sleep apnea, heart failure, liver disease, and kidneys?

SURMOUNT-OSA tested tirzepatide in people with obstructive sleep apnea and obesity [12]. Secondary analyses from that trial covered patient-reported outcomes [13] and sleep-apnea-related cardiometabolic risk [14]. SURPASS-CVOT examined cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes [11]. SUMMIT tested tirzepatide in heart failure with preserved ejection fraction and obesity [15]. SYNERGY-NASH tested it in metabolic dysfunction-associated steatohepatitis (MASH) with liver fibrosis [16], and SYNERGY-Outcomes is a master protocol testing multiple agents in metabolic dysfunction-associated steatotic liver disease, registered as NCT07165028 [17].

The kidney evidence published so far is post hoc or exploratory: a post-hoc analysis of SURPASS-4 versus insulin glargine [18], pooled kidney parameters from SURMOUNT-1 and -2 [19], and prespecified exploratory kidney analyses of SURPASS-CVOT [20]. TREASURE-CKD, registered as NCT05536804, is a study of tirzepatide in overweight or obesity with chronic kidney disease [21].

What evidence exists on muscle and body composition?

A sub-study within SURMOUNT-1 measured body composition using DXA scans [22]. A separate trial called LEAN-PREP has published only its protocol so far; it is a randomized trial of resistance exercise plus protein supplementation during semaglutide or tirzepatide therapy [23]. Whether tirzepatide causes muscle loss is not answered by anything verified for this page.

Has tirzepatide been tested in children?

Yes, for type 2 diabetes. SURPASS-PEDS was a randomized, double-blind, placebo-controlled phase 3 trial in children and adolescents with type 2 diabetes [24]. No pediatric obesity trial results appear in the publications reviewed for this page.

What are the newest results?

SURMOUNT-MAINTAIN was a multicenter, double-blind, randomized, placebo-controlled US trial testing tirzepatide for maintaining weight reduction in people with obesity [25].

REDEFINE 4 was an open-label head-to-head trial of CagriSema versus tirzepatide in people with obesity. Novo Nordisk announced that CagriSema demonstrated 23% weight loss and that the primary endpoint was not achieved [26].

SURPASS-EARLY compared tirzepatide with intensified conventional care over 2 years in early type 2 diabetes [27].

What does the evidence still not cover?

There is no completed cardiovascular outcome trial of tirzepatide in people with obesity who do not have diabetes; SURMOUNT-MMO, a study of tirzepatide on reduction of morbidity and mortality in adults with obesity, is still listed as a study (NCT05556512) [10]. There is no type 1 diabetes result; SURPASS-T1D is registered as NCT06914895 [28].

Real-world comparisons of tirzepatide and semaglutide conflict: STEER examined cardiovascular outcomes in people with overweight or obesity [29], while a retrospective propensity-matched cohort study examined outcomes in obesity plus type 2 diabetes [30]. Both are observational studies of records, not randomized head-to-head trials, so they cannot establish the same level of certainty as SURPASS-2 [2, 29, 30].

Finally, the funding pattern is part of the published record: Eli Lilly and Company funded SURPASS-1, -2, -3, SURPASS J-mono, and SURMOUNT-1 and -2, and several authors on those publications are Lilly employees and shareholders [1, 2, 3, 4, 6, 7].

This page describes published trial results only. It is not medical advice, and it does not suggest any dose for any person. Decisions about starting, stopping, or choosing a dose of tirzepatide belong with a clinician who knows your health history.

Sources

  1. PubMed. 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.
  2. PubMed. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes.
  3. PubMed. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial.
  4. PubMed. Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial.
  5. PubMed. Tirzepatide versus insulin glargine as second-line or third-line therapy in type 2 diabetes in the Asia-Pacific region: the SURPASS-AP-Combo trial.
  6. PubMed. Tirzepatide Once Weekly for the Treatment of Obesity.
  7. PubMed. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial.
  8. PubMed. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial.
  9. PubMed. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity.
  10. ClinicalTrials.gov. A Study of Tirzepatide (LY3298176) on the Reduction on Morbidity and Mortality in Adults With Obesity.
  11. PubMed. Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes.
  12. PubMed. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity.
  13. PubMed. Effect of tirzepatide treatment on patient-reported outcomes among SURMOUNT-OSA participants with obstructive sleep apnea and obesity.
  14. PubMed. Tirzepatide on obstructive sleep apnea-related cardiometabolic risk: secondary outcomes of the SURMOUNT-OSA randomized trial.
  15. PubMed. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity.
  16. PubMed. Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis.
  17. ClinicalTrials.gov. A Master Protocol of Multiple Agents in Adults With Metabolic Dysfunction-Associated Steatotic Liver Disease (SYNERGY-Outcomes).
  18. PubMed. Effects of tirzepatide versus insulin glargine on kidney outcomes in type 2 diabetes in the SURPASS-4 trial: post-hoc analysis of an open-label, randomised, phase 3 trial.
  19. PubMed. Kidney Parameters with Tirzepatide in Obesity with or without Type 2 Diabetes.
  20. PubMed. A comparison of the effects of tirzepatide and dulaglutide on major kidney events in people with type 2 diabetes: pre-specified exploratory analyses of the SURPASS-CVOT trial.
  21. ClinicalTrials.gov. A Study of Tirzepatide (LY3298176) in Participants With Overweight or Obesity and Chronic Kidney Disease With or Without Type 2 Diabetes.
  22. PubMed. Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight.
  23. PubMed. LEAN mass Preservation with Resistance Exercise and Protein during semaglutide and tirzepatide therapy (LEAN-PREP study): a protocol for a randomised controlled trial.
  24. PubMed. Efficacy and safety of tirzepatide in children and adolescents with type 2 diabetes (SURPASS-PEDS): a randomised, double-blind, placebo-controlled, phase 3 trial.
  25. PubMed. Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial.
  26. GlobeNewswire. Novo Nordisk A/S: CagriSema demonstrated 23% weight loss in an open-label head-to-head REDEFINE 4 trial in people with obesity; the primary endpoint was not achieved. February 23, 2026.
  27. PubMed. Tirzepatide Versus Intensified Conventional Care After 2 Years of Treatment in Early Type 2 Diabetes: A Randomized Clinical Trial.
  28. ClinicalTrials.gov. Clinical study record NCT06914895.
  29. PubMed. Semaglutide and tirzepatide effects on cardiovascular outcomes in people with overweight or obesity in the real world (STEER).
  30. PubMed. Comparative real-world outcomes of tirzepatide vs semaglutide in patients with obesity and type2 diabetes: A retrospective propensity-matched cohort study.

Frequently asked questions

How much weight did people lose on tirzepatide in the trials, by dose?

In SURMOUNT-1, adults with obesity lost an average of 15.0% of body weight on 5 mg, 19.5% on 10 mg, and 20.9% on 15 mg over 72 weeks, versus 3.1% on placebo. On the 15 mg dose, 57% lost at least 20% of their body weight.

Did tirzepatide beat semaglutide head to head, and at which dose?

Yes, in SURPASS-2, but against semaglutide 1 mg, the diabetes dose, not the higher obesity dose. HbA1c fell 2.30 points on tirzepatide 15 mg versus 1.86 on semaglutide 1 mg, and weight differed by up to 5.5 kg in tirzepatide's favor. No published trial compares it with semaglutide 7.2 mg.

How much weight loss happened in people who also had type 2 diabetes?

In SURMOUNT-2, adults with obesity and type 2 diabetes lost 12.8% to 14.7% over 72 weeks, versus 15.0% to 20.9% in SURMOUNT-1, where diabetes was excluded [6, 7]. The trials enrolled different populations, so the figures describe each group separately rather than a controlled comparison.

How much does tirzepatide lower HbA1c compared with insulin?

Against titrated insulin degludec, HbA1c fell 1.93 to 2.37 points on tirzepatide versus 1.34 on insulin, and 82% to 93% reached HbA1c below 7.0% versus 61%. Against insulin glargine in the Asia-Pacific trial, tirzepatide lowered HbA1c 2.24 to 2.49 points versus 0.95.

Does tirzepatide reduce heart attacks and strokes, or is that still unproven?

SURPASS-CVOT examined cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes; its result was not verified for this page. No completed cardiovascular outcome trial in obesity without diabetes appears in the publications reviewed here — SURMOUNT-MMO is still listed as a study.

Does tirzepatide cause muscle loss?

The publications reviewed here do not answer that with a simple yes or no. A SURMOUNT-1 sub-study measured body composition with DXA scans, but its fat- and lean-mass figures were not verified for this page. LEAN-PREP, a trial of resistance exercise plus protein during treatment, has published only its protocol.

Is tirzepatide approved for sleep apnea, liver disease, or kidney disease?

This page reports trial evidence, not approvals, and no approval status is covered by the publications reviewed here. Trials exist in each area: SURMOUNT-OSA in obstructive sleep apnea and obesity, SYNERGY-NASH in MASH with liver fibrosis, and kidney analyses that are post hoc or exploratory rather than outcome trials [18, 19, 20].

Has tirzepatide been tested in children?

Yes. SURPASS-PEDS was a randomized, double-blind, placebo-controlled phase 3 trial in children and adolescents with type 2 diabetes. Its sample size and results were not verified for this page. No pediatric obesity trial results appear in the publications reviewed here.

This article summarizes FDA labeling, published research and company information current as of September 14, 2026. It is not medical advice and does not replace a conversation with your own healthcare provider. How we research and verify.