Could metformin modulate cardiovascular outcomes differently with DPP-4 inhibitors compared with SGLT2 inhibitors? - 12/08/21
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Highlights |
• | The place of metformin as first-line therapy in patients with T2DM and high CV risk has been recently challenged. |
• | Preliminary data suggested that metformin may favourably influence CV effects of DPP-4is but potentially reduce CV protection by SGLT2is. |
• | Meta-analyses of CVOTs showed that metformin does not modify the neutral impact of DPP-4is neither the reduction in major CV events with SGLT2is. |
• | Our results do not challenge the preferred position of metformin as first line therapy still recommended by the 2020 ADA-EASD consensus report. |
Abstract |
Aims |
Preliminary data have suggested that metformin might potentiate cardiovascular (CV) protection by dipeptidyl peptidase-4 inhibitors (DPP-4is), but reduce CV protection by sodium–glucose cotransporter type-2 inhibitors (SGLT2is), in patients with type 2 diabetes (T2DM) at high CV-related risk. For this reason, the present meta-analyses aimed to compare metformin moderation of the CV effects of the two pharmacological classes.
Methods |
Major adverse CV events (3-point MACEs) were counted in high-risk patients with T2DM treated with or without metformin as background therapy in five CV outcome trials with DPP-4is (SAVOR–TIMI 53, EXAMINE, TECOS, CARMELINA, CAROLINA) involving 24,821 patients (17,870 with and 6951 without metformin) and 2550 events (1696 with and 854 without metformin), and four trials with SGLT2is (EMPA-REG OUTCOME, CANVAS, DECLARE–TIMI 58, VERTIS CV) involving 24,563 patients (19,090 with and 5473 without metformin) and 1829 events (1300 with and 529 without metformin).
Results |
DPP-4is failed to reduce 3-point MACEs in both metformin users (OR: 0.96, 95% CI: 0.89–1.03) and non-users (OR: 1.05, 95% CI: 0.95–1.16), with no heterogeneity between trials and no significant between-subgroup differences (P = 0.4074), whereas SGLT2is significantly reduced 3-point MACEs in both patients with (OR: 0.91, 95% CI: 0.84–0.98) and without (OR: 0.81, 95% CI: 0.71–0.91) metformin, but again with no heterogeneity between trials and no significant between-subgroup differences (P = 0.2977). Overall, metformin non-users had a poorer risk profile than metformin users.
Conclusion |
Our meta-analyses involving a larger number of trials than before have revealed that background metformin therapy has no significant influence on either the neutral impact of DPP-4is or the positive impact of SGLT2is on CV events (3-point MACEs) in T2DM patients at high CV risk.
Il testo completo di questo articolo è disponibile in PDF.Keywords : Cardiovascular outcome trial, Gliflozin, Gliptin, 3-point MACEs, Meta-analysis, Metformin
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Vol 47 - N° 4
Articolo 101209- luglio 2021 Ritorno al numero
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