Does Gender Influence the Cardiovascular Benefits Observed with Sodium Glucose Co-Transporter-2 (SGLT-2) Inhibitors? A Meta-Regression Analysis

Abstract

IntroductionAlthough a large recent trial had shown improved cardiovascular outcomes of diabetic patients on sodium glucose co-transporter-2 (SGLT-2) inhibitors, the influence of gender differences on such outcomes is not known. Thus, we aimed to assess the impact of gender on such outcomes in the patients with type 2 diabetes mellitus receiving SGLT-2 inhibitors.MethodsA search of electronic databases was conducted for all randomized trials comparing SGLT-2 inhibitors with placebo in patients with diabetes mellitus. Primary outcomes were all-cause mortality and cardiovascular mortality. Random effects meta-regression was conducted using the percentage of women included in the SGLT-2 inhibitor arm of each trial with a P value of <0.1 for statistical significance.ResultsA total of 22,256 patients from 26 trials were included. The overall odds ratio (OR) of all-cause mortality [OR = 0.72, 95% confidence interval (CI) 0.60–0.86, P < 0.001, I 2 = 0%], and cardiovascular mortality (OR = 0.67, 95% CI 0.53–0.84, P = 0.001, I 2 = 23%) were lower with SGLT-2 inhibitors. Meta-regression suggested a possible incremental increase in the OR for all-cause mortality and cardiovascular mortality as the percentage of women in the SGLT-2 inhibitor arm increased (P = 0.07 and 0.08, respectively).ConclusionGender might influence the cardiovascular benefits observed with SGLT-2 inhibitors in patients with type 2 diabetes mellitus.Electronic supplementary materialThe online version of this article (doi:10.1007/s40119-016-0075-1) contains supplementary material, which is available to authorized users.

Dose‐dependent glucosuria of DWP16001, a novel selective sodium–glucose cotransporter‐2 inhibitor, in healthy subjects

“…Since differences including cardiovascular results between men and women have been reported for some SGLT-2 inhibitors, it is necessary to explore sex-associated differences in the effects of DWP16001 in further studies. 38,39 Nevertheless, since there were similarities in the PD response between healthy subjects and patients for other SGLT-2 inhibitors, the results of this study are thought to provide meaningful information for clinical use. Oropharyngeal pain 3 (37.50) Oropharyngeal pain 1 (12.50) 1 Chest discomfort 1 (12.50) 1 Chest pain 1 (12.50) 1 Chills 1 (9.09) 1 Cold sweat 1 (12.50) 1 1 (12.50) 1 Dysuria 1 (12.50) 1 Urinary retention 1 (12.50) 1 Balanoposthitis 1 (12.50) 1 All data presented as number of subjects (percentage of subjects) number of events.…”

“…Because a relatively small number of healthy male subjects participated, information on the AEs of DWP16001 was limited. Since differences including cardiovascular results between men and women have been reported for some SGLT‐2 inhibitors, it is necessary to explore sex‐associated differences in the effects of DWP16001 in further studies 38,39 . Nevertheless, since there were similarities in the PD response between healthy subjects and patients for other SGLT‐2 inhibitors, the results of this study are thought to provide meaningful information for clinical use.…”

Underrepresentation of Women in Recent Landmark Kidney Trials: The Gender Gap Prevails

“… 2 A 2016 meta-analysis of 26 SGLT-2i trials demonstrated a relatively smaller reduction in cardiovascular mortality when the proportion of women enrolled in the trials increased. 3 In addition to sex-based differences in efficacy, women experience a higher proportion of some drug-related adverse events with SGLT2i (primarily genital and urinary infections) compared with men. 4 , 5 Sex-specific differences in efficacy have also been reported with GLP1-RAs, namely, a larger relative reduction in cardiovascular events in women compared with men, 6 but more frequent adverse events (particularly gastrointestinal events).…”

Pharmacokinetic and pharmacodynamic interaction of DWP16001, a sodium–glucose cotransporter 2 inhibitor, with gemigliptin and metformin in healthy adults

“…It is necessary to explore the sex‐associated differences in the effects of DWP in further studies, as differences in PD (i.e. cardiovascular results) between men and women were reported for some SGLT‐2 inhibitors 24,25 . Second, drug interactions were explored in healthy subjects in this study.…”