Research review · Sources checked October 15, 2026 · Mounjaro heart indication and Lilly’s Q3 2026 results added October 29, 2026

Published July 17, 2026 · Updated October 30, 2026

Tirzepatide: approvals and key trials

Tirzepatide is a once-weekly agonist of the GIP and GLP-1 receptors. FDA approved it as Mounjaro for type 2 diabetes on May 13, 2022, and as Zepbound for chronic weight management on November 8, 2023.[1][2]

Approved uses

Mounjaro is approved as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes. It was first approved for adults;[1] its current label (revised August 2026) covers adults and children 10 and older.[7] Since August 27, 2026, Mounjaro has also been approved “to reduce the risk of major adverse cardiovascular (CV) events (CV death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus who are at high risk for these events,” according to FDA’s approval letter. The same supplement updated the label’s warning about diabetic retinopathy complications.[6][7] Zepbound is approved for chronic weight management in adults with a BMI of 30 or more, or 27 or more with at least one weight-related condition.[2] In December 2024 FDA approved Zepbound for moderate to severe obstructive sleep apnea in adults with obesity, the first medication approved for that condition.[3] Zepbound’s current label, also revised August 2026, lists weight management and sleep apnea and does not include the heart indication.[8]

SURPASS-CVOT: heart outcomes versus Trulicity

The heart indication rests on SURPASS-CVOT, which randomized 13,299 adults with type 2 diabetes and established heart or blood-vessel disease to weekly Mounjaro (up to 15 mg) or Trulicity (dulaglutide) 1.5 mg, a GLP-1 drug that already carried a heart indication. Median follow-up was 210.1 weeks, about four years.[7][9] The combined rate of cardiovascular death, heart attack or stroke was 12.1% on Mounjaro versus 13.0% on Trulicity, a hazard ratio of 0.92 (95.3% CI 0.83 to 1.01). The label says Mounjaro was non-inferior to Trulicity and that “superiority to dulaglutide was not established.”[7] Deaths from any cause were 8.5% versus 10.1% (hazard ratio 0.84, 95% CI 0.75 to 0.94), a secondary result.[7] The full results, published in the New England Journal of Medicine in December 2025, report 12.2% versus 13.1% because they count the 13,165 patients left after 134 were excluded for not meeting the entry criteria; the paper gives P = 0.003 for non-inferiority and P = 0.09 for superiority, and notes more gastrointestinal side effects on tirzepatide, with other adverse events appearing similar.[11] Lilly describes this as an 8% lower rate of those events and calls Mounjaro the first GIP and GLP-1 drug proven to lower that risk in this group.[9] Our reading: the trial shows Mounjaro protects the heart at least about as well as a drug with proven benefit; it did not show it protects better. The death figure is encouraging but was not the main question, so treat it as a signal rather than a proven difference. Lilly funded the trial.

SURMOUNT-1: weight loss

In adults with obesity or overweight without diabetes, mean weight change at week 72 was −15.0% (5 mg), −19.5% (10 mg), and −20.9% (15 mg), versus −3.1% with placebo.[4] For a critical read of the design, safety, sponsor role, denominators, and weight regain after stopping, see the How much weight will you lose on Zepbound or Mounjaro? (SURMOUNT-1 teardown).

SURPASS-2: versus semaglutide in type 2 diabetes

All three tirzepatide doses lowered HbA1c more than semaglutide 1 mg (−2.01, −2.24, and −2.30 points versus −1.86) and were noninferior and superior to it. Weight reductions were also greater. Gastrointestinal events were the most common adverse events in both groups (nausea 17–22% versus 18%).[5]

Heart failure. Neither the Mounjaro nor the Zepbound label lists heart failure as an approved use.[7][8] No randomized trial has compared tirzepatide with semaglutide in heart failure. An observational US insurance-claims study published October 29, 2026 linked tirzepatide to fewer heart failure hospital stays than semaglutide, with no difference in deaths, in adults with type 2 diabetes and heart failure with preserved ejection fraction (HFpEF); a study of this kind cannot show cause and effect. For the numbers, an earlier claims study that found no clear difference, and the placebo-controlled trials, see Zepbound vs Wegovy: heart failure (HFpEF).

Lilly’s third-quarter 2026 results (October 29, 2026)

In its October 29 earnings release, Lilly said worldwide Mounjaro revenue rose 65% from a year earlier to $10.7 billion in the third quarter: $5.0 billion in the US (up 41%) and $5.7 billion elsewhere (up 93%). Lilly said US Zepbound revenue rose 48% to $5.3 billion, and that the fall in its average US prices was “primarily driven by Zepbound.”[10] The release lists the Mounjaro heart approval among the quarter’s regulatory milestones and says Lilly expects Phase 3 trials of EloraTZP, a combination of eloralintide and tirzepatide, “to start in Q4 2026.”[10] Those are company plans and statements, covered by the release’s forward-looking-statement caveats. Our reading: sales figures say how widely tirzepatide is being used, not how well it works for any one person; the release contained no new efficacy or safety data on tirzepatide. For the amylin combination, see our amylin drugs teardown.

Compounded versions

Compounded tirzepatide is not the FDA-approved product. See the compounding enforcement explainer.

This page summarizes published research and regulatory documents. It is not medical advice and does not recommend starting, stopping, or changing any medication.