Results of the STEP 2 trial presented at the recently concluded European Association for the Study of Diabetes (EASD) Annual Meeting held in Stockholm, Sweden show that treatment with higher doses of semaglutide (2.4 mg) led to greater weight loss, which translated to greater odds of achieving A1c levels <5.7% among the overweight or obese type 2 diabetes patients.¹ The number of patients who achieved improvement in glycemic control across all HbA1c thresholds in the three groups of participants increased with greater decrements in body weight.

Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue, which is currently approved for the treatment of type 2 diabetes in adults in doses up to 1 mg administered subcutaneously once weekly.²

The STEP 2 trial randomized 1210 overweight/obese adults (BMI ≥27 kg/m2) with type 2 diabetes to receive semaglutide 2.4 mg (n=404), semaglutide 1.0 mg (n=403) or placebo (n=403) to 68 weeks. The participants were also instructed to increase physical activity and eat a low-calorie diet. The objective of the study was to establish an association between weight loss and glycemic control among the overweight/obese diabetic patients with semaglutide. The study endpoint was the mean change in body weight (%) in individuals who attained A1c <5.7% at week 20 and 68 from the baseline. The percentage of individuals with A1c <5.7%, <6.5% or <7.0% at week 68 was also determined.

The reduction in body weight (mean) at the end of the study was greater among patients who reached HbA1c level less than 5.7%.

At 68 weeks, the decrease in body weight (mean) was 14.6% with semaglutide 2.4 mg, 9.5% with semaglutide 1.0 mg and 7.8% with placebo among participants who achieved HbA1c <5.7% at 20 weeks. Among those who did not attain A1c <5.7% at 20 weeks, the corresponding percentages for decrease in body weight were 10.0%, 7.2% and 3.2%, respectively.

Among those who achieved A1c <5.7% at 68 weeks were 16.7% (semaglutide 2.4 mg), 13.5% (semaglutide 1.0 mg) and 11.6% (placebo) compared to 8.8%, 6.2% and 2.9%, respectively, who did not achieve HbA1c <5.7% at 68 weeks. “The proportions of participants with HbA1c <5.7% at week 20/week 68 were 14%/25% (semaglutide 2.4 mg), 10%/18% (semaglutide 1.0 mg) and 3%/2% (placebo).”

More patients receiving semaglutide 2.4 mg and 1 mg achieved loss of body weight (≥5%, ≥10%, ≥15%) across all categories and A1c (<5.7%, <6.5%, <7.0%) than those given placebo.

Weight management has now become an integral component of management of type 2 diabetes. Weight loss helps in glycemic control by enhancing insulin sensitivity. Results of the The Diabetes Remission Clinical Trial (DiRECT) conducted by UK researchers show that participants who lost more than 10 kg and sustained this weight loss achieved diabetes remission.³

However, the benefits of weight loss extend beyond just glycemic control. It also helps control other cardiometabolic risk factors such as cholesterol, TGs, blood pressure. Type 2 diabetes is marked by underlying low grade inflammation. An additional advantage of weight loss is reduction in inflammation, which also prevents or delays onset of complications. The outcome is reduced demand for pharmacotherapy and better quality of life.

References

1. Davies M, et al. Abstract #499. Associations between weight loss and glycaemic control with once weekly semaglutide 1.0 mg and 2.4 mg in the STEP 2 trial. Diabetologia. 2022; 65(Suppl 1):S254-55.
2. Ozempic (semaglutide) injection prescribing information, Revised 2020. US FDA. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209637s003lbl.pdf
3. Lean ME, et al. Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol. 2019 May;7(5):344-355.