Weekly Semaglutide 2.4 mg Shows Promise in Treating Obesity and Prediabetes: Results from STEP 10 Phase 3 Trial

UK: A study published in The LANCET Diabetes and Endocrinology revealed that Semaglutide 2.4 mg led to significantly greater weight loss and a higher rate of reversion to normoglycemia compared to placebo in individuals with obesity and prediabetes.

Prof. Barbara M. McGowan, MD, Department of Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation Trust et. al., conducted a study to evaluate the efficacy and safety of semaglutide 2.4 mg for weight management and glycemic control in participants with obesity and prediabetes.

The STEP 10 study was a randomized, double-blind, parallel-group, phase 3 trial conducted at 30 sites across Canada, Denmark, Finland, Spain, and the UK. It included participants aged 18 and older with a BMI of 30 kg/m² or higher and prediabetes, as defined by the UK National Institute for Health and Care Excellence criteria (either an HbA1c of 6.0–6.4% [42–47 mmol/mol] or fasting plasma glucose [FPG] of 5.5–6.9 mmol/L at screening). Participants were randomly assigned in a 2:1 ratio to receive once-weekly subcutaneous semaglutide 2.4 mg or placebo, alongside diet and physical activity counseling, for 52 weeks, followed by a 28-week off-treatment period. The primary endpoints were the percentage change in body weight and the proportion of participants who reverted to normoglycemia (HbA1c <6.0% [<42 mmol/mol] and FPG <5.5 mmol/L) at week 52, analyzed in all randomly assigned participants based on intention to treat. Selective safety data were collected from participants who received at least one dose of the study drug.

The key findings of the study are as follows:

• A total of 138 participants were assigned to the semaglutide 2.4 mg group, while 69 were assigned to the placebo group. Of these, 71% were female and 29% were male, with 88% of participants identified as White.
• Baseline characteristics of the participants included a mean age of 53 years, mean bodyweight of 111.6 kg, mean BMI of 40.1 kg/m², mean waist circumference of 120.1 cm, mean HbA1c of 5.9% (41.3 mmol/mol), and mean fasting plasma glucose (FPG) of 5.9 mmol/L.
• The semaglutide 2.4 mg group showed a significantly greater reduction in body weight at week 52, with an average decrease of 13.9%, compared to a 2.7% reduction in the placebo group. The estimated treatment difference was –11.2%, with a 95% confidence interval (CI) of –13.0 to –9.4, and the result was statistically significant (p<0.0001).
• A higher proportion of participants in the semaglutide 2.4 mg group reverted to normoglycemia at week 52, with 81% achieving this outcome compared to 14% in the placebo group. The odds ratio for reversion to normoglycemia was 19.8, with a 95% CI of 8.7 to 45.2, and the result was statistically significant (p<0.0001).
• Serious adverse events were reported in 9% of participants in both the semaglutide 2.4 mg group and the placebo group. However, adverse events leading to treatment discontinuation were more common in the semaglutide group (6%) compared to the placebo group (1%). Importantly, no new safety signals were identified during the trial.

The study concluded that Semaglutide 2.4 mg led to a significantly greater reduction in body weight and a higher rate of reversion to normoglycemia compared to placebo in participants with obesity and prediabetes. The safety and tolerability profile of Semaglutide 2.4 mg was consistent with previous studies and aligned with the known characteristics of the GLP-1 receptor agonist class. These findings suggest that Semaglutide 2.4 mg could be a promising treatment option for individuals with obesity and prediabetes to help achieve reversion to normoglycemia.

Reference

McGowan BM, Bruun JM, Capehorn M, Pedersen SD, Pietiläinen KH, Muniraju HAK, Quiroga M, Varbo A, Lau DCW; STEP 10 Study Group. Efficacy and safety of once-weekly semaglutide 2·4 mg versus placebo in people with obesity and prediabetes (STEP 10): a randomised, double-blind, placebo-controlled, multicentre phase 3 trial. Lancet Diabetes Endocrinol. 2024 Jul 29:S2213-8587(24)00182-7. doi: 10.1016/S2213-8587(24)00182-7. Epub ahead of print. PMID: 39089293.