SURMOUNT-2 shows smaller but substantial weight loss in type 2 diabetes

Results from SURMOUNT-2, a phase 3 trial of once-weekly tirzepatide in adults who have both type 2 diabetes and obesity or overweight, were published June 26, 2023. After 72 weeks, participants on tirzepatide lost an average of 12.8% (10 mg) or 14.7% (15 mg) of their body weight, compared with 3.2% on placebo ^[1].

The trial enrolled 938 adults across seven countries between March 29, 2021, and April 10, 2023, out of 1,514 people screened ^[1]. To qualify, participants had to be at least 18 years old with a body mass index of 27 kg/m² or higher and an HbA1c between 7% and 10% (53–86 mmol/mol) ^[1]. They were randomly assigned in equal numbers to tirzepatide 10 mg (n=312), tirzepatide 15 mg (n=311), or placebo (n=315), with participants, investigators and the sponsor all blinded to assignment ^[1]. The study is registered as NCT04657003 ^[2].

What the numbers showed

At the start, the average participant weighed 100.7 kg (about 222 pounds), with a BMI of 36.1 kg/m² and an HbA1c of 8.02% ^[1]. The group averaged 54.2 years old; 51% were female, 76% were White, and 60% were Hispanic or Latino ^[1].

The difference versus placebo was 9.6 percentage points for the 10 mg dose and 11.6 percentage points for the 15 mg dose, both statistically significant (p<0.0001) ^[1]. On the second co-primary endpoint — losing at least 5% of body weight — 79% to 83% of tirzepatide participants hit that mark, compared with 32% on placebo ^[1].

Side effects followed the pattern seen with other incretin drugs. The most common problems were gastrointestinal: nausea, diarrhea and vomiting, mostly mild to moderate, with fewer than 5% of participants stopping treatment because of them ^[1]. Serious adverse events were reported in 68 participants (7%) overall. Two deaths occurred in the tirzepatide 10 mg group; investigators did not consider either related to the study drug ^[1]. The trial was funded by Eli Lilly and Company, and several authors are Lilly employees and shareholders ^[1].

Why it matters for patients

The headline weight-loss figures in people with type 2 diabetes are lower than the numbers often quoted from obesity trials in people without diabetes. Researchers have long observed that GLP-1 and dual-agonist drugs produce less weight loss when diabetes is present. SURMOUNT-2 did not include a comparison group of people without diabetes, so this trial by itself cannot quantify that gap — those side-by-side numbers are not in this source ^[1].

What the trial does establish is that a double-digit percentage loss is achievable in this group. For someone starting near the trial average of about 222 pounds, a 14.7% reduction works out to roughly 33 pounds over about 17 months ^[1]. The authors described the result as "substantial and clinically meaningful" ^[1].

The 5% threshold matters too, because it is the level commonly used in obesity research as a marker of health benefit. Roughly four in five people on tirzepatide reached it, versus about one in three on placebo plus lifestyle support ^[1].

One design detail is worth noting: the primary analysis used a "treatment-regimen estimand," meaning it counted results regardless of whether people stopped the drug or started rescue medication for their blood sugar ^[1]. That approach tends to produce more conservative numbers than analyses that only count people who stayed on treatment.

What is not yet known

The published abstract does not report how much HbA1c changed, how weight loss differed by sex or ethnicity, or what happened after the 72-week treatment period ended ^[1]. Longer-term durability and cardiovascular outcomes in this specific population are not addressed by this trial.