A phase 2 liver trial where the add-on drug didn't help — and the base drug quietly did
Read the Sunday Brief →

Study wrapper · #1033

Oral Semaglutide and CV Benefits in the SOUL Trial: How Do Baseline or Changes in HbA1c or BMI Affect Clinical Outcomes?

Inzucchi SE, Abdul Ghani R, Deanfield J, et al. The Journal of clinical endocrinology and metabolism. 2026.
SupportedRCTMentions: Semaglutide

Editor's note

A post hoc analysis of the large, double-blind SOUL cardiovascular outcomes trial of oral semaglutide in high-risk type 2 diabetes. The cardiovascular benefit was more pronounced at higher baseline HbA1c and with greater HbA1c reduction, yet consistent across BMI, suggesting the effect is not simply weight-mediated. As a post hoc subgroup analysis, the interaction findings are hypothesis-generating despite the trial's strong randomized design.

Plain-language abstract

In a post hoc analysis of the SOUL trial, oral semaglutide's cardiovascular benefit was greater in people with higher starting blood sugar and larger blood-sugar reductions, but was consistent regardless of body-mass index or weight change. The overall trial found a 14% reduction in major cardiovascular events.