Treatment effects of semaglutide consistent across race and ethnicity subgroups

In a post-hoc analysis of 3 STEP trials among patients with overweight or obesity, with or with no T2D, the efficacy and safety of semaglutide 2.4 mg did not differ by race or ethnicity.

This summary is based on the publication of Rubino D, Angelene H, Fabricatore A, et al. - Efficacy and safety of semaglutide 2.4 mg by race and ethnicity: A post hoc analysis of three randomized controlled trials. Obesity (Silver Spring). 2024 Jul;32(7):1268-1280. doi: 10.1002/oby.24042

Introduction and methods

Background

In clinical trials of pharmacological therapies for obesity, racial and ethnic minority groups are often underrepresented [1]. Moreover, some obesity intervention trials have shown higher attrition rates and lower efficacy in these populations [2,3]. The GLP-1RA semaglutide was evaluated in 5 STEP (Semaglutide Treatment Effect in People with Obesity) trials [4], which involved a large cohort of adults with overweight or obesity, giving the opportunity to examine treatment effects by race and ethnicity.

Aim of the study

In a post-hoc analysis of 3 STEP trials, the authors examined the efficacy and safety of semaglutide in patients with overweight or obesity, stratified by race and ethnicity.

Methods

The STEP trials were US- or global-based, multicenter, placebo-controlled, double‐blind, phase 3 RCTs in which the efficacy and safety of subcutaneous semaglutide 2.4 mg once weekly versus placebo were investigated in patients with overweight or obesity, with or with no T2D. For this analysis, data were pooled from the STEP 1 and 3 trials (n=2572), which had similar patient populations, study duration, and endpoints [5,6]. As the STEP 2 trial included patients with comorbid T2D (n=807), data from this trial were assessed separately [7]. Participants self-identified their race and ethnicity: White (STEP 1 and 3: 75.3%; STEP 2: 59.4%), Black (8.8% vs. 8.9%), Asian (10.6% vs. 27.3%), or other racial group (5.3% vs. 4.4%); and Hispanic or Latino (13.9% vs. 11.9%) or non-Hispanic or non-Latino ethnicity (83.9% vs. 88.1%).

Outcomes

The primary efficacy endpoint was the estimated treatment difference (ETD) in percent body weight change from baseline to 68 weeks for semaglutide versus placebo. Secondary efficacy endpoints were changes in metabolic outcomes (waist circumference and systolic blood pressure) from baseline to 68 weeks and the OR of reaching a body weight reduction of ≥5%, ≥10%, and ≥15% for semaglutide versus placebo by 68 weeks. Safety assessment included the frequencies of adverse events, serious adverse events, and adverse events leading to discontinuation of the study drug.

Main results

Efficacy

• In the STEP 1 and 3 trial pooled sample, the ETD in percent body weight reduction from baseline to 68 weeks for semaglutide versus placebo ranged from 9.3% to 12.5% across all subgroups, with no interaction by race (P=0.0758) or ethnicity (P=0.4042).
• In the STEP 2 trial sample, the ETD in percent body weight reduction ranged from 4.5% to 7.3%, with no interaction by race (P=0.1547) or ethnicity (P=0.8589).
• Race and ethnicity also did not influence the ETD in waist circumference for semaglutide versus placebo in the STEP 1 and 3 pooled sample and STEP 2 sample (all P for interaction≥0.25), nor the ETD in systolic blood pressure (all P for interaction≥0.10).
• In addition, there were no statistically significant interactions between the odds of reaching ≥5%, ≥10%, or ≥15% weight reduction and race or ethnicity in both data sets (all P for interaction≥0.12).

Safety

• The safety profile of semaglutide was generally consistent across racial and ethnic subgroups in both data sets.
• The most common adverse events were nausea, vomiting, diarrhea, and constipation.
• The frequencies of changes in treatment (dose reduction, temporary interruption, and permanent treatment discontinuation) were overall consistent across all subgroups in both data set.

Conclusion

In this post-hoc analysis of 3 STEP trials among patients with overweight or obesity, with or with no T2D, the efficacy and safety of semaglutide 2.4 mg did not differ by race or ethnicity. The authors conclude their “results highlight the need for equitable access to effective therapies for underserved groups of people with obesity to reduce health disparities.”

Find this article online at Obesity (Silver Spring).

References

1. Anekwe CV, Jarrell AR, Townsend MJ, Gaudier GI, Hiserodt JM, Stanford FC. Socioeconomics of obesity. Curr Obes Rep. 2020;9:272-279.
2. Harvey JR, Ogden DE. Obesity treatment in disadvantaged population groups: where do we stand and what can we do? Prev Med. 2014;68:71-75.
3. Osei-Assibey G, Kyrou I, Adi Y, Kumar S, Matyka K. Dietary and lifestyle interventions for weight management in adults from minority ethnic/non-White groups: a systematic review. Obes Rev. 2010;11:769-776.
4. Kushner RF, Calanna S, Davies M, et al. Semaglutide 2.4 mg for the treatment of obesity: key elements of the STEP trials 1 to 5. Obesity (Silver Spring). 2020;28:1050-1061.
5. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384:989-1002.
6. Wadden TA, Bailey TS, Billings LK, et al. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: the STEP 3 randomized clinical trial. JAMA. 2021;325:1403-1413.
7. Davies M, Faerch L, Jeppesen OK, et al. Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021;397:971-984.