Does race/ethnicity affect the safety, efficacy of semaglutide?

A post hoc analysis of the Semaglutide Treatment Effect in People with Obesity (STEP) clinical trials has shown that the treatment effect and safety profile of semaglutide 2.4 mg, compared with placebo, are consistent across racial and ethnic subgroups.

“We did not observe any significant differences in the treatment effect or safety profile by racial or ethnic subgroups,” the investigators said. “These results highlight the need for equitable access to effective therapies for underserved groups of people with obesity to reduce health disparities.”

The STEP clinical trials assessed both the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg. In the current study, the investigators pooled data from STEP 1 and 3 for analysis and examined those from STEP 2 separately. They carried out all analyses using data from racial and ethnic subgroups.

The estimated treatment difference in percent body weight change for semaglutide 2.4 mg as compared with placebo served as the primary outcome.

Majority of the participants were White (STEP 1 and 3: 75.3 percent; STEP 2: 59.4 percent), while the rest were Black (STEP 1 and 3: 8.8 percent; STEP 2: 8.9 percent), Asian (STEP 1 and 3: 10.6 percent; STEP 2: 8.9 percent), or other racial group (STEP 1 and 3: 5.3 percent; STEP 2: 4.4 percent).

Additionally, ethnicities were either Hispanic/Latino (STEP 1 and 3: 13.9 percent; STEP 2: 11.9 percent) or not Hispanic/Latino (STEP 1 and 3: 83.9 percent; STEP 2: 88.1 percent). [Obesity 2024;32:1268-1280]

The treatment effect of semaglutide 2.4 mg did not significant differ across racial (STEP 1 and 3: p≥0.07; STEP 2: p≥0.15) or ethnic groups (STEP 1 and 3: p≥0.40; STEP 2: p≥0.85). Similarly, the safety profile of the study drug was consistent across all subgroups.

“The treatment effect of semaglutide was statistically significant versus placebo and clinically relevant across all racial and ethnic subgroups in STEP 1 and 3 and STEP 2,” the investigators said. “All subgroups across both samples demonstrated good tolerability.”

Chronic diseases

This post hoc analysis was conducted given the underrepresentation in clinical trials of racial and ethnic minority groups, who may have disproportionate access to healthcare and high rates of poverty and unemployment. These social factors are associated with a greater risk of chronic diseases, such as obesity. [Front Endocrinol (Lausanne) 2021;12:706978; Nat Rev Drug Discov 2022;21:201-223]

“When examining the treatment effect of semaglutide 2.4 mg by race and ethnicity across three phase IIIa clinical trials, we found no evidence of interactions,” the investigators said.

“This suggests similar efficacy for percent reduction in body weight (measured continuously and categorically) as well as reductions in waist circumference and systolic blood pressure, and the odds of achieving ≥5-, ≥10-, or ≥15-percent weight loss for participants who described their race as Asian, Black, or White, and ethnicity as Hispanic or Latino, or not Hispanic or Latino.”

However, one interaction effect approached significance (p=0.07). In STEP 1 and 3, the estimated treatment difference (ETD) for percent body weight reduction among Asians was lower by nearly 2 percent and 3 percent than Black or White participants, respectively. In STEP 2, the ETD was about 2‒3-percent lower among Asian or Black participants than their White counterparts.

“These differences in treatment effect may in part be explained by the lower mean baseline BMI in the Asian subgroup compared with the Black and White racial subgroups, which may have resulted in a reduced weight loss threshold for Asian participants to achieve a healthy weight,” the investigators said.