SURMOUNT-2

Most obesity drug trials deliberately exclude people with type 2 diabetes, because diabetes blunts weight loss and complicates the results. SURMOUNT-2 did the opposite: it enrolled only adults who had both obesity and type 2 diabetes, which is the population most clinicians actually see. Garvey and colleagues published it in The Lancet in 2023.

938 adults were randomized to tirzepatide 10 mg, tirzepatide 15 mg or placebo for 72 weeks. Baseline mean body weight was 100.7 kg, mean BMI 36.1, and mean HbA1c 8.02% — a group with genuinely uncontrolled diabetes, not borderline numbers. Notably, 60% of participants were Hispanic or Latino, unusual breadth for a trial of this kind.

At week 72, mean body weight fell 12.8% on tirzepatide 10 mg and 14.7% on 15 mg, versus 3.2% on placebo. Between 79% and 83% of tirzepatide participants lost at least 5% of their body weight, against 32% on placebo. Gastrointestinal side effects dominated, were mostly mild to moderate, and led fewer than 5% to stop treatment.

The context that makes those numbers meaningful: in SURMOUNT-1, which enrolled people without diabetes, tirzepatide produced larger average losses. That gap is the expected pattern, not a flaw in either trial — diabetes and the medications used to treat it both work against weight loss. Comparing a diabetes trial’s percentage with a non-diabetes trial’s and concluding one drug underperformed is the most common misreading of this literature.

Worth asking your clinician: whether your other diabetes medications help or hinder weight (insulin and sulfonylureas typically hinder), whether doses of those need to come down as a GLP-1 takes effect, and what HbA1c target you are aiming for alongside the weight goal. Our SURMOUNT-2 deep dive, Zepbound drug page, and interaction checker cover the combinations that need attention.