GLP-1RA reduces risk of MACE regardless of metformin use in T2DM

Semaglutide reduced cardiovascular events regardless of metformin use: a post hoc exploratory subgroup analysis of SUSTAIN 6 and PIONEER 6

Presented at the EASD 2021 by: Mansoor Husain, MD - Toronto, ON, Canada

Introduction and methods

This post hoc analysis of the SUSTAIN 6 and PIONEER 6 trials investigated whether use of metformin affects the benefits of semaglutide on CV and metabolic outcomes in patients with T2DM.

SUSTAIN 6 tested once weekly s.c. semaglutide vs. placebo and PIONEER 6 tested daily oral semaglutide vs. placebo in patients with T2DM aged ≥50 years and with established CVD or ≥60 years with CV risk factors. In SUSTAIN 6, the minimum treatment duration was 104 weeks. There was no minimum treatment duration in PIONEER 6 and median time in trial was 69 weeks. The current analysis pooled data from SUSTAIN 6 and PIONEER 6 and included in total 6480 patients (4881 with baseline metformin and 1599 without baseline metformin). The primary endpoint of this analysis was MACE (defined as CV death, non-fatal MI and non-fatal stroke). Metabolic outcomes (change in HbA1c and body weight) and safety outcomes (serious adverse events and severe hypoglycemic events) were analyzed as well.

Main results

• Compared to patients with baseline metformin, patients without baseline metformin had a higher CV risk score, were older, had lower eGFR and higher body weight. More patients without baseline metformin received concomitant insulin and less received sulphonylureas compared to patients with baseline metformin.
• Semaglutide reduced the risk of MACE compared to placebo regardless of baseline metformin use (With metformin: HR 0.70, 95%CI 0.55-0.89; without metformin: HR 0.86, 95%CI 0.60-1.22; P for interaction=0.355).
• HbA1c and body weight reductions from baseline with semaglutide compared to placebo were similar in both metformin subgroups (P for interaction=0.42 and 0.51, respectively).
• Serious adverse events and severe hypoglycemic events were also comparable for the two metformin groups (P for interaction=0.993 and 0.969, respectively).

Conclusion

This post hoc analysis showed that semaglutide reduced the risk of CV outcomes compared to placebo in patients with T2DM regardless of metformin use. Metabolic outcomes and safety outcomes were also similar across metformin subgroups.

-Our reporting is based on the information provided at the EASD Virtual Meeting–