Abstract Background Several real-world studies have already shown that combined therapy with sodium-glucose cotransporter-2 inhibitors (SGLT2i), and glucagon-like peptide-1 receptor agonists (GLP1ra), regarding monotherapy reduce mortality in patients with diabetes. However, it might differ between women and men because of their disparate risk burdens. Purpose Analyse the differential benefits of combined therapy (SGLT2i and GLP1ra) vs. monotherapy (SGLT2i or GLP1ra) between women and men regarding all-cause mortality. Methods We performed a non-concurrent observational prospective study of patients with type 2 diabetes mellitus (T2DM) who were prescribed SGLT2i and/or GLP1ra. Inclusion criteria: All patients with T2DM ≥ 18 years old who started taking SGLT2i or/and GLP1ra from January 2018 to June 2022, and follow-up until October 2022. A multinomial propensity score was performed for treatment adjustment in women and men. The multivariate Cox regression analysis was determined by the hazard rate (HR) of age, risk factors, and treatment in women and men for all-cause mortality. Results We included 15.118 patients with T2DM (11.601 with SGLT2i, 1.069 with GLP1ra, and 2.448 with both treatments) from the treatment initiation. Women were represented by 41%. The median follow-up was 33 months. Women were older (7162-78 vs. 6759-75, 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) (Figure 1a). Men had a higher risk of all-cause mortality than women in this population (HR 95% CI 1,50 1,28-1,75) (Figure 1b). Combined therapy (GLP1ra and SGLT2i) 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; the Cox regression survival curve showed a lower risk of all-cause mortality in women (Figure 2a) and men (Figure 2b) with combined therapy regarding monotherapy, 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) (Figure 2c). Conclusions Combined therapy (SGLT2i and GLP1ra) vs. monotherapy was associated with a lower risk of all-cause mortality in patients with T2DM regardless of sex, nevertheless, a higher benefit was observed in women regarding men.
Vega et al. (Sat,) studied this question.