STEP 2

STEP 2 is the trial that tells people with type 2 diabetes what to expect from Wegovy. It randomized 1,210 adults with overweight or obesity and type 2 diabetes to semaglutide 2.4 mg, semaglutide 1.0 mg, or placebo, all with lifestyle support, for 68 weeks. Davies and colleagues published it in The Lancet in March 2021.

Estimated mean body-weight change at week 68 was -9.6% on semaglutide 2.4 mg versus -3.4% on placebo, a treatment difference of 6.2 percentage points. At least 5% of body weight was lost by 68.8% of the 2.4 mg group versus 28.5% on placebo. Adverse events were more common on the drug (87.6% versus 76.9%), driven by gastrointestinal complaints that were mostly mild to moderate.

The comparison worth making is with STEP 1, which used the same 2.4 mg dose for 68 weeks in people without diabetes and reported roughly 15% weight loss. Same drug, same dose, same duration — the diabetes population lost about a third less. This is the single most useful expectation-setting fact in the whole literature, and it is the one most often left out of marketing.

Why the gap exists is not fully settled, but insulin resistance, the glucose-lowering effect itself, and weight-promoting diabetes medications all plausibly contribute. The inclusion of a 1.0 mg arm also makes STEP 2 unusual: it lets you see the dose-response within a single trial rather than inferring it across studies.

Worth asking your clinician: whether your expected result should be benchmarked against STEP 1 or STEP 2, whether any of your current medications work against weight loss, and how A1c and weight targets should be sequenced. Our STEP 2 deep dive, SURMOUNT-2 (the tirzepatide equivalent), and weight-loss projection tool help set a realistic target.