Combined SGLT2i and GLP1ra therapy reduces all-cause mortality in people with diabetes, with greater benefit in women

Abstract

Background and aims

Combined therapy, sodium-glucose cotransporter 2 inhibitors (SGLT2i), and glucagon-like peptide-1 receptor agonists (GLP1ra) reduce all-cause mortality in patients with diabetes. We aimed to analyse the differential behaviour of combined therapy between women and men regarding all-cause mortality.

Methods and results

This is a retrospective observational cohort study. Using “Big data” according to electronic medical records in the Santiago-Barbanza health area, which covers 450,000 patients. Out of 15,118 patients, 41 % were women. The median follow-up was 33 months. Women were older (71 [62–78] vs. 67 [59–75], p: <0.001) and with a higher incidence of obesity (53 % vs. 41 %, p: <0.001), meanwhile, men presented more coronary artery disease (CAD) (19 % vs. 9 %, p: <0.001). The multinomial propensity score and multivariate Cox regression were used for statistical analysis. All-cause mortality was compared between combined vs. monotherapy in women or men. Men had a higher risk of all-cause mortality than women in this population (HR [95 % CI] 1.50 [1.28–1.75]). Combined regarding monotherapy (GLP1ra (HR [95 % CI] 0.19 [0.14–0.27]), or SGLT2i (HR [95 % CI] 0.30 [0.23–0.40]), and treatment duration (HR [95 % CI] 0.95 [0.94–0.96] were associated with lower risk of all-cause mortality; with higher benefit in women (GLP1ra (HR [95 % CI] 0.14 [0.08–0.27]), or SGLT2i (HR [95 % CI] 0.18 [0.11–0.30]) regarding men (HR [95 % CI] 0.25 [0.16–0.40] for GLP1ra, and HR [95 % CI] 0.41 [0.29–0.58] for SGLT2i).

Conclusions

Combined therapy vs. monotherapy was associated with a lower risk of all-cause mortality in patients regardless of sex. Nevertheless, a higher benefit was observed in women regarding men.