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- W3113013783 abstract "Over the last two decades, the large majority of clinical guidelines on the treatment of hyperglycemia in subjects with type 2 diabetes have suggested metformin as the first-line glucose-lowering treatment alongside lifestyle changes to reach personalized glycemic targets. Recently, the European Society of Cardiology recommended using glucagon-like peptide 1 receptor agonists (GLP-1RA) or sodium–glucose cotransporter 2 inhibitors (SGLT-2i) as first-line glucose-lowering therapy in subjects with type 2 diabetes at high or very high risk of cardiovascular disease, ahead of metformin treatment, to reduce cardiovascular events (1).Following the European Society of Cardiology guidelines, several analyses have investigated whether the cardiovascular effects of GLP-1RA or SGLT-2i would differ in relation to the use of metformin. Some of these studies reported a “statistically significant” difference (i.e., interaction) in the cardiovascular effects of SGLT-2is, whereby subjects with metformin have a lower cardiovascular protection from SGLT-2i, leading to several hypotheses about the possible pharmacological mechanisms. Interpreting interaction results, however, may be difficult, as they suffer from well-known drawbacks, including limited statistical power (2). For overcoming this problem and identifying who may be most likely to benefit from a specific treatment, trial-specific interactions may be combined with a meta-analytical approach (3).In this study, we systematically investigated the differences in the treatment effect of incretins (GLP-1RA and dipeptidyl peptidase 4 inhibitors [DPP-4i]) and SGLT-2i on cardiovascular outcomes according to metformin use. We included DPP-4i given their overlapping pharmacodynamics with GLP-1RAs and the previous evidence of interactions with metformin (4).On 5 October 2020, we searched for randomized controlled trials (RCTs) in adults with type 2 diabetes reporting incretin or SGLT-2i treatment effect for the primary cardiovascular outcome (major adverse cardiovascular event [MACE]) stratified by baseline metformin use; details of the search, included trials, and risk of bias are available on request. We …" @default.
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- W3113013783 date "2020-12-17" @default.
- W3113013783 modified "2023-10-16" @default.
- W3113013783 title "Use of Metformin and Cardiovascular Effects of New Classes of Glucose-Lowering Agents: A Meta-analysis of Cardiovascular Outcome Trials in Type 2 Diabetes" @default.
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- W3113013783 doi "https://doi.org/10.2337/dc20-2080" @default.
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