Efficacy and safety of GLP-1RAs with or without baseline SGLT-2i: post hoc analysis of the SUSTAIN 10 trial

Presented at the EASD 2021 by: Matthew Capehorn, MD – Rotherham, United Kingdom

Introduction and methods

Evidence of safety and efficacy of using the combination of GLP-1RAs and SGLT2i is limited, but this information is valuable for clinical decision-making. There is some evidence though that there is added benefit of the combination of GLP-1RAs and SGLT2i in reducing HbA1c and body weight compared to single use of either agent. PIONEER 4 and SUSTAIN 6 showed that adding semaglutide to an SGLT2 inhibitor resulted in added benefit.

In the SUSTAIN- 6 trial, the effect of semaglutide was compared to liraglutide after 30 weeks in patients with diabetes. Patients were stratified by background medication.

In this post hoc analysis, efficacy (change from baseline in HbA1c, body weight and SBP) and safety with the GLP-1RAs semaglutide and liraglutide, in patients with and without background SGLT2 inhibitors was examined. Therefore, there were 4 groups: semaglutide minus SGLT2i (n=217), semaglutide plus SGLT2i (n=73), liraglutide minus SGLT2i (n=218), liraglutide plus SGLT2i (n=69). Characteristics and background medications were similar across treatment arms. SGLT2i used were empagliflozin, dapaglifozin, and canaglifozin.

Main results

• Regardless of SGLT2i use, semaglutide and liraglutide reduced HbA1c, body weight and SBP from baseline to week 30.
• There were no unexpected safety concerns in patients receiving a combination of GLP-1RA and SGLT2 inhibitor. Premature treatment discontinuations due to adverse events were low with semaglutide and liraglutide in both SGLT2i subgroups.

Conclusion

The GLP-1RAs semaglutide and liraglutide reduced HbA1c, body weight and SBP, regardless of background use of an SGLT2 inhibitor, in patients with diabetes.

In the discussion, dr. Capehorn said that these findings are in line with other studies and analyses investigating the addition of a GLP-1RA to SGLT2i. In addition, these findings expand the evidence on the safety and efficacy of combining GLP-1RA and SGLT2is, and are valuable for decision-making.

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