SUSTAIN FORTE supports the Ozempic 2 mg dose

A clinical trial called SUSTAIN FORTE found that a higher dose of once-weekly semaglutide, the drug sold as Ozempic for type 2 diabetes, worked better than the standard 1.0 mg dose at lowering blood sugar and body weight, without a meaningful increase in side effects ^[1].

The trial enrolled 961 adults with type 2 diabetes that was not well controlled on metformin, with or without a sulfonylurea drug ^[1]. Participants had an average HbA1c, a measure of long-term blood sugar, of 8.9% at the start, and an average BMI of 34.6 ^[1]. Half were randomly assigned to 2.0 mg of semaglutide once a week, and half to 1.0 mg, for 40 weeks ^[1].

By week 40, HbA1c fell by 2.2 percentage points in the 2.0 mg group compared with 1.9 percentage points in the 1.0 mg group, a statistically significant difference ^[1]. Body weight dropped by 6.9 kg (about 15 pounds) in the 2.0 mg group versus 6.0 kg (about 13 pounds) in the 1.0 mg group ^[1]. When the researchers used a stricter analysis that counted everyone as originally assigned, regardless of whether they stayed on treatment, the HbA1c difference held up, though the weight-loss difference was smaller and did not reach statistical significance ^[1].

Side effects were similar between the two doses. Gastrointestinal problems, the most commonly reported adverse events, occurred in 34% of people on 2.0 mg and 31% on 1.0 mg ^[1]. Serious adverse events were reported in 4% of the 2.0 mg group and 5% of the 1.0 mg group ^[1]. Three deaths occurred during the trial, one in the 1.0 mg group and two in the 2.0 mg group ^[1]. Almost all participants finished the study: 96% in the 2.0 mg group and 98% in the 1.0 mg group ^[1].

The trial was funded by Novo Nordisk, the maker of semaglutide, and several of the study authors reported financial ties to the company, including two who are full-time Novo Nordisk employees and shareholders ^[1]. The study authors concluded that the 2.0 mg dose gives doctors and patients a way to intensify treatment for people whose diabetes isn't controlled well enough on the 1.0 mg dose ^[1]. A companion commentary published alongside the study, written by a different author, discussed the broader question of how much value comes from increasing GLP-1 drug doses ^[1].

Why it matters for patients

About 20% to 30% of people taking semaglutide 1.0 mg do not reach their blood sugar goals, according to the study's background rationale ^[1]. These findings suggest a higher, 2.0 mg dose can offer an added option for those patients without a different safety trade-off, at least over the 40 weeks studied ^[1]. The extra weight loss, roughly one kilogram more than the 1.0 mg dose, was a secondary benefit of the trial, not its main purpose, since the study was designed to test blood sugar control in people with type 2 diabetes ^[1].

It's not yet known from this study how the 2.0 mg dose performs over longer periods, or how it compares with other diabetes or weight-loss options such as tirzepatide, sold as Mounjaro. The trial also only enrolled adults already on metformin, with or without a sulfonylurea, so the results may not apply to people on other treatment combinations.

What happens next

The trial ran from June 19 to November 28, 2019, and results were published July 1, 2021, in a peer-reviewed journal ^[1]. The study is registered on ClinicalTrials.gov under identifier NCT03989232 ^[1]. Longer-term data and real-world use of the 2.0 mg dose were not addressed in this report and are not yet known from the sources reviewed here.