Semaglutide 2.4 mg returns 81% of adults with obesity and prediabetes to normal blood sugar in STEP 10

Adults with obesity and prediabetes who took weekly semaglutide 2.4 mg injections for a year were far more likely to return to normal blood sugar than those who received a placebo, according to results of the STEP 10 trial published on July 29, 2024 ^[1].

At the end of 52 weeks, 103 of 127 participants taking semaglutide, or 81%, had reverted to normoglycemia, compared with 9 of 64 on placebo, or 14% ^[1]. The trial defined normoglycemia as an HbA1c below 6.0% and a fasting plasma glucose below 5.5 mmol/L ^[1]. The odds ratio was 19.8 (95% CI 8.7 to 45.2; p<0.0001) ^[1].

Body weight fell by an average of 13.9% with semaglutide and 2.7% with placebo, an estimated treatment difference of minus 11.2 percentage points (95% CI minus 13.0 to minus 9.4; p<0.0001) ^[1].

How the trial was run

STEP 10 was a randomized, double-blind, placebo-controlled phase 3 trial at 30 sites in Canada, Denmark, Finland, Spain and the UK. No US sites took part ^[1]. Between Sept. 16 and Dec. 29, 2021, researchers assigned 207 participants in a 2-to-1 ratio: 138 to semaglutide 2.4 mg and 69 to placebo ^[1]. Everyone received diet and physical activity counseling for 52 weeks, followed by a 28-week period with no treatment ^[1].

Participants were 18 or older with a body mass index of at least 30 and prediabetes according to UK National Institute for Health and Care Excellence criteria, meaning a screening HbA1c of 6.0% to 6.4% or a fasting plasma glucose of 5.5 to 6.9 mmol/L ^[1]. Of the 207 participants, 147 (71%) were female and 60 (29%) were male; 183 (88%) were White ^[1]. Their average age was 53, average body weight 111.6 kg, average BMI 40.1, and average HbA1c 5.9% ^[1].

Serious adverse events occurred in 12 participants (9%) on semaglutide and 6 (9%) on placebo. Adverse events that led to stopping treatment occurred in 8 participants (6%) on semaglutide and 1 (1%) on placebo. The paper reports no new safety signals and says the safety and tolerability profile matched earlier studies and the GLP-1 receptor agonist class ^[1].

The trial was funded by Novo Nordisk, which makes semaglutide. Three authors are Novo Nordisk employees and shareholders, and several others report consulting fees, speaking fees or research grants from Novo Nordisk and other drugmakers ^[1].

Why it matters for patients

Prediabetes means blood sugar is higher than normal but not yet in the range of type 2 diabetes. The trial measured blood sugar at one year, and about eight in ten participants on semaglutide were back in the normal range at that point ^[1].

What the trial did not measure is whether that shift lowers the chance of developing type 2 diabetes later, or whether blood sugar stays normal after the drug is stopped. The 28-week off-treatment phase was part of the study design, but those results are not reported in this paper ^[1].

The population studied was narrow in some ways: mostly female, mostly White, with an average BMI of 40, and all enrolled outside the United States ^[1]. How closely those results apply to a broader group of US patients has not been established. The study tested a 2.4 mg weekly injection dose specifically ^[1].

The authors write that the findings support the potential use of semaglutide 2.4 mg as a treatment option for people with obesity and prediabetes to achieve reversion to normoglycemia ^[1]. No regulatory decision or label change for prediabetes has been reported.

What happens next

The trial is registered as NCT05040971 and is complete ^[1]. Results from the 28-week off-treatment period have not been reported, and it has not been disclosed whether the manufacturer plans to seek an approved prediabetes use. A separate commentary in the same journal issue, titled "Prediabetes remission in people with obesity," discusses the findings; no abstract is available for it ^[1].

The study appears in The Lancet Diabetes & Endocrinology, with a 2024 copyright held by Elsevier Ltd. ^[1].