Semaglutide reduces hsCRP levels across different treatment settings: post hoc analyses of SUSTAIN and PIONEER trials

Presented at the EASD 2021 by: Ofri Mosenzon, MD – Jerusalem, Israel

Introduction and methods

It has been reported that high-sensitivity C-reactive protein (hsCRP) is elevated in patients with T2DM. There is limited evidence on the effects of GLP-1RAs on hsCRP.

This exploratory analysis examined the effect of semaglutide (subcutaneous and oral) vs. comparators on hsCRP levels in patients with T2DM.

Data on hsCRP in four semaglutide trials were used: SUSTAIN 3 (once-weekly SC semaglutide vs. once-weekly exenatide), PIONEER 1 (once-daily oral semaglutide vs. placebo), PIONEER 2 (once-daily oral semaglutide vs. once-daily empagliflozin) and PIONEER 5 (one-daily oral semaglutide vs placebo). Baseline characteristics of patients in PIONEER 5 were different from those of patients in the other trials.

Main results

• Treatment with semaglutide resulted in greater reduction of hsCRP from baseline compared to comparators in SUSTAIN 3, PIONEER 1 and PIONEER 2 (estimated treatment ratio ranged from 0.70-0.75) (a non-significant reduction was observed in PIONEER 5).
• The reduction of hsCRP by semaglutide was partially explained by changes in HbA1c (percentage mediated ranged from 22.6-38.9%).
• There was a wide distribution of the percentage explaining reduction in hsCRP by changes in body weight (from 5.3 to 50.9%).
• When combining the percentages that explain the reduction in hsCRP by changes in HbA1c and body weight there was a wide distribution between the trials.

Conclusion

This analysis showed that semaglutide (subcutaneous and oral) reduced hsCRP when compared to comparators in patients with diabetes, which may partially be explained by reductions in HbA1c and body weight.

More trials, such as the SOUL and SELECT, will provide more insights in the effect of semaglutide on inflammation and CV effect in patients with T2DM and obesity. Currently, renal outcomes with semaglutide are studied in patients with T2DM and CKD in the FLOW trial, said dr. Mosenzon.

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