The SURPASS program: tirzepatide's glucose-lowering evidence
The diabetes trials that led to tirzepatide's first approval, as Mounjaro.
A coordinated trial set
SURPASS was a series of phase-3 trials testing tirzepatide in type 2 diabetes against placebo and active comparators including semaglutide and insulin. Together they formed the evidence base for tirzepatide's first regulatory approval, as Mounjaro, for glycemic control in type 2 diabetes.
Large A1c reductions
Across the program, tirzepatide produced substantial reductions in A1c — commonly in the range of 1.9 to 2.6 percentage points at higher doses, depending on the trial and background therapy. High proportions of participants reached A1c targets such as below 7%, and many reached normoglycemic-range values, an unusually strong result for a single agent.
Glucose and weight together
Unlike many older diabetes drugs that are weight-neutral or cause weight gain, tirzepatide produced meaningful weight loss across SURPASS, often increasing with dose. This dual benefit — lower glucose and lower weight — is central to its clinical appeal and led to the separate obesity program (SURMOUNT).
Beating strong alternatives
SURPASS trials compared tirzepatide against placebo, semaglutide 1 mg (SURPASS-2), and titrated basal insulin, among others. Tirzepatide generally produced greater A1c and weight improvements than these comparators, with gastrointestinal side effects the main trade-off.
Caveats
These are diabetes trials; the medication's role and dosing in any individual is a clinical decision. A dedicated cardiovascular outcomes trial (SURPASS-CVOT) was conducted to assess long-term heart outcomes. Compounded tirzepatide is not FDA-approved.
Why reaching normal-range A1c is notable
One striking feature across SURPASS was the high proportion of participants who reached aggressive glycemic targets, including A1c values in or near the normal (non-diabetic) range on higher doses. For a single agent in type 2 diabetes, that is unusual and reflects the magnitude of tirzepatide's effect. Two cautions keep this in perspective. First, trial populations are selected and supported in ways that can produce better results than typical real-world use. Second, an impressive A1c number is a surrogate marker; what ultimately matters to patients is long-term outcomes — complications, hospitalizations, cardiovascular events — which is why dedicated outcome trials exist. Still, the depth of glucose lowering, achieved alongside weight loss rather than weight gain, is a genuine departure from many older therapies and explains much of the clinical enthusiasm. As always, the right target and therapy for an individual is a clinical decision that weighs benefits, risks, other conditions and cost.
Primary sources
- Frías JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide once weekly in type 2 diabetes (SURPASS-2). N Engl J Med. 2021;385(6):503-515.
- Nicholls SJ, et al. Cardiovascular outcomes with tirzepatide versus dulaglutide (SURPASS-CVOT): trial design. Am Heart J. 2024.
- U.S. Food and Drug Administration. Mounjaro and Zepbound (tirzepatide) prescribing information. Eli Lilly and Company.
Citations are provided for educational reference. This article summarizes published research in plain language and is not medical advice. Always consult a licensed clinician.
Common questions
What is the SURPASS program?
A set of phase-3 trials (SURPASS-1 to -5 and others) that established tirzepatide's glucose-lowering efficacy in type 2 diabetes and supported its approval as Mounjaro.
How much does tirzepatide lower A1c?
In SURPASS trials, higher doses commonly lowered A1c by about 1.9 to 2.6 percentage points, depending on the trial and background treatment.
Does tirzepatide help weight in diabetes too?
Yes — across SURPASS it produced meaningful weight loss in addition to glucose lowering, unlike many older diabetes drugs.