A meta-analysis of 18 cohort studies with over 1.1 million participants found that combining SGLT2 inhibitors with GLP-1 drugs reduced major cardiac events by 44% and cardiovascular death by 74% compared to monotherapy.
74% CV mortality reductionSGLT2i + GLP-1 RA combination vs. monotherapy across 18 cohort studies with 1.16M participants
What the researchers found
Combination SGLT2i + GLP-1 RA therapy reduced MACE by 44% (RR 0.56), cardiovascular mortality by 74% (RR 0.26), and kidney composite endpoint by 52% (RR 0.48) vs. monotherapy.
Why it matters
This is the strongest real-world evidence yet that combining these two drug classes produces additive or synergistic cardiorenal protection, supporting dual therapy as a potential new standard for high-risk diabetic patients.
How the study worked
Systematic review and meta-analysis of 18 cohort studies (1,164,774 participants) with GRADE certainty assessment and ROBINS-I bias evaluation.
What this study cannot tell us
All observational studies; residual confounding cannot be excluded. Evidence certainty rated low to very low by GRADE. Safety data were too sparse to pool.
How to read the evidence
Large meta-analysis of cohort studies with robust methodology and GRADE assessment, but observational design limits certainty (rated low to moderate).
When this study was published
Published in 2026, searching databases through May 2025.
The bigger picture
While randomized trials are needed for definitive proof, this meta-analysis of real-world data provides compelling evidence for a paradigm shift toward combination cardiometabolic therapy in type 2 diabetes.
Questions still open
- Will randomized trials (e.g., dedicated SGLT2i + GLP-1 RA combination trials) confirm these observational findings?
- Which patient subgroups benefit most from dual therapy vs. monotherapy?
- Are the benefits driven by additive or truly synergistic mechanisms?
Common questions
Should I take both an SGLT2 inhibitor and a GLP-1 drug?
Are there more side effects from taking both drugs together?
Read the original research
Effectiveness and safety of combining SGLT2 inhibitors and GLP-1 receptor agonists in individuals with type 2 diabetes: a systematic review and meta-analysis of cohort studies.
Diabetologia, 69(1), 36-49
Citation
Colombijn, Julia M T; de Leijer, Jan F; Visseren, Frank L J; Verhaar, Marianne C; van Raalte, Daniël H; Sattar, Naveed; Vernooij, Robin W M; van Sloten, Thomas T. (2026). Effectiveness and safety of combining SGLT2 inhibitors and GLP-1 receptor agonists in individuals with type 2 diabetes: a systematic review and meta-analysis of cohort studies.. Diabetologia, 69(1), 36-49. https://doi.org/10.1007/s00125-025-06565-6