Could metformin modulate cardiovascular outcomes differently with DPP-4 inhibitors compared with SGLT2 inhibitors?
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…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 24,821 participants or records.
Read the paper
Related studies
- Metformin as an adjuvant in breast cancer treatment
- Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?
- Aberrant HSF1 signaling activation underlies metformin amelioration of myocardial infarction in mice
- Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines
- Protein Interaction Network for Identifying Vascular Response of Metformin (Oral Antidiabetic)
- Preventing Long COVID With Metformin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.