SURMOUNT-2: tirzepatide for obesity in people with type 2 diabetes

People with type 2 diabetes lose less weight on incretin drugs than people without it. SURMOUNT-2 is the tirzepatide trial that puts a number on that gap.

What the trial asked

Whether tirzepatide 10 mg or 15 mg once weekly reduces body weight, compared with placebo, in adults who have both obesity (or overweight) and type 2 diabetes.

Design

Phase 3, double-blind, randomised 1:1:1, placebo-controlled, run in seven countries. Treatment lasted 72 weeks. The primary analysis used the treatment-regimen estimand, which counts participants regardless of whether they stopped the drug or started rescue glucose-lowering therapy. Efficacy and safety were analysed in everyone randomised.

Who was enrolled

Between March 2021 and April 2023, 1514 adults were screened and 938 were randomised: 312 to 10 mg, 311 to 15 mg, 315 to placebo. Entry required a BMI of 27 or higher and an HbA1c of 7 to 10 percent. Mean age was 54.2 years; 51 percent were female; 76 percent were White and 60 percent Hispanic or Latino. Baseline mean weight was 100.7 kg, BMI 36.1 and HbA1c 8.02 percent.

Primary endpoint and result

Coprimary endpoints at week 72: percent change in body weight, and a reduction of 5 percent or more.

All p values were below 0.0001. Between 79 and 83 percent of tirzepatide participants reached the 5 percent threshold, against 32 percent on placebo.

Key secondary results

The abstract does not itemise secondary endpoints beyond the 5 percent responder rate. HbA1c results are in the full paper and are not repeated here because the abstract does not state them.

Adverse events and discontinuation

The most frequent adverse events were gastrointestinal (nausea, diarrhoea, vomiting), mostly mild to moderate, with few leading to discontinuation (under 5 percent). Serious adverse events were reported by 68 participants (7 percent) overall. Two deaths occurred in the 10 mg group; the investigators did not consider them related to treatment.

Funding and registration

Eli Lilly and Company. ClinicalTrials.gov NCT04657003.

What this trial does not show

• Compared with SURMOUNT-1, the same doses produced about 5 to 6 fewer percentage points of weight loss. The trial does not explain why; it only documents the difference in a diabetic population.
• No 5 mg arm was tested here, so the label's lowest maintenance dose has no SURMOUNT-2 weight number.
• It is a placebo comparison. For tirzepatide against semaglutide in diabetes, see SURPASS-2, which measured HbA1c rather than weight as its primary endpoint.
• It does not report cardiovascular or kidney outcomes.

Where the numbers come from

PubMed abstract of the primary paper (PubMed 37385275), fetched 4 September 2026. Where the abstract gives a standard error rather than a confidence interval, the standard error is shown. See the weight-management versus diabetes trials guide for why the two populations are analysed separately.