Does Gender Influence the Cardiovascular Benefits Observed with Sodium Glucose Co-Transporter-2 (SGLT-2) Inhibitors? A Meta-Regression Analysis
Cardiology and Therapy - 2016
Tóm tắt
Although 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. A 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. A 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). Gender might influence the cardiovascular benefits observed with SGLT-2 inhibitors in patients with type 2 diabetes mellitus.
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Tài liệu tham khảo
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–28.
Juutilainen A, Kortelainen S, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Gender difference in the impact of type 2 diabetes on coronary heart disease risk. Diabetes Care. 2004;27(12):2898–904.
Peters SA, Huxley RR, Woodward M. Diabetes as risk factor for incident coronary heart disease in women compared with men: a systematic review and meta-analysis of 64 cohorts including 858,507 individuals and 28,203 coronary events. Diabetologia. 2014;57:1542–51.
Saad M, Mahmoud AN, Elgendy IY, et al. Cardiovascular outcomes with sodium–glucose cotransporter-2 inhibitors in patients with type II diabetes mellitus: a meta-analysis of placebo-controlled randomized trials. Int J Cardiol. 2017;228:352–58.
Food And Drug Administration. FDA briefing document: endocrine and metabolic drug advisory committee meeting. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM508422.pdf. Accessed 28 June 2016.
Taub ME, Ludwig-Schwellinger E, Ishiguro N, et al. Sex-, species-, and tissue-specific metabolism of empagliflozin in male mouse kidney forms an unstable hemiacetal metabolite (M466/2) that degrades to 4-hydroxycrotonaldehyde, a reactive and cytotoxic species. Chem Res Toxicol. 2015;28:103–15.
Vrhovac I, Eror DB, Klessen D, et al. Localizations of Na+-d-glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart. Pflugers Arch. 2015;467:1881–98.