Three cardiovascular outcome trials failed to show superiority of DPP4 inhibitors compared with placebo in patients with type 2 diabetes mellitus and high cardiovascular risk, a rather disappointing finding. Now, a post hoc subgroup analysis suggests that patients treated with metformin at baseline might benefit from DPP4 inhibitors in contrast with metformin non-users.
References
Scheen, A. J. Cardiovascular effects of gliptins. Nat. Rev. Cardiol. 10, 73–84 (2013).
Standl, E. et al. Integration of recent evidence into management of patients with atherosclerotic cardiovascular disease and type 2 diabetes. Lancet Diabetes Endocrinol. 5, 391–402 (2017).
White, W. B. et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N. Engl. J. Med. 369, 1327–1335 (2013).
Scirica, B. M. et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N. Engl. J. Med. 369, 1317–1326 (2013).
Green, J. B. et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N. Engl. J. Med. 373, 232–242 (2015).
Crowley, M. J. et al. Metformin use may moderate the effect of DPP-4 inhibitors on cardiovascular outcomes. Diabetes Care http://dx.doi.org/10.2337/dc17-1528 (2017).
Hernandez, A. V. et al. Subgroup analyses in therapeutic cardiovascular clinical trials: are most of them misleading? Am. Heart J. 151, 257–264 (2006).
Sun, X. et al. How to use a subgroup analysis: users' guide to the medical literature. JAMA 311, 405–411 (2014).
Migoya, E. M. et al. Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1. Clin. Pharmacol. Ther. 88, 801–808 (2010).
Wang, F. et al. Combination therapy of metformin plus dipeptidyl peptidase-4 inhibitor versus metformin plus sulfonylurea and their association with a decreased risk of cardiovascular disease in type 2 diabetes mellitus patients. Medicine (Baltimore) 96, e7638 (2017).
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The author declares that no competing interests are directly relevant to the content of this manuscript. A.J.S. has received lecturer,scientific adviser and clinical investigator fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck Sharp & Dohme, NovoNordisk, Sanofi and Servier. A.J.S. was a clinical investigator in the TECOS, LEADER, EMPA-REG OUTCOME and CANVAS-R trials.
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Scheen, A. Metformin — a cardiovascular moderator of DPP4 inhibitors?. Nat Rev Endocrinol 14, 8–9 (2018). https://doi.org/10.1038/nrendo.2017.154
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DOI: https://doi.org/10.1038/nrendo.2017.154
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