Combining SGLT-2 Inhibitors With GLP-1 Drugs Linked to 29% Lower Death Risk in Diabetes Patients | Research

The takeaway

Adding a GLP-1 receptor agonist to an SGLT-2 inhibitor was associated with 29% lower mortality and 22% less heart failure compared to SGLT-2 inhibitors alone.

29% lower mortality
Adding a GLP-1 RA to SGLT-2 inhibitor therapy vs. SGLT-2 inhibitor alone in 21,664 matched pairs

What the researchers found

Combining SGLT-2 inhibitors with GLP-1 receptor agonists was associated with a 29% lower risk of death from any cause compared to SGLT-2 inhibitors alone (HR 0.71, 95% CI 0.63–0.80) in over 21,000 matched pairs of type 2 diabetes patients. The combination also showed a 19% reduction in the cardiovascular composite outcome (HR 0.81) and a 22% reduction in heart failure risk (HR 0.78). These benefits were consistent across patient subgroups and multiple sensitivity analyses.

Why it matters

SGLT-2 inhibitors and GLP-1 receptor agonists each have proven cardiovascular benefits individually, but real-world evidence for combining them has been limited. This large study provides strong support for the additive benefit of using both drug classes together — a strategy increasingly recommended in diabetes guidelines but not yet tested in a dedicated randomized trial.

The numbers in context

n=21,664 matched pairs · Median follow-up 1.3 years · All-cause mortality HR 0.71 (95% CI 0.63–0.80) · CV composite HR 0.81 (0.74–0.88) · Heart failure HR 0.78 (0.68–0.89)

How the study worked

Real-world cohort study using nationwide German BARMER health claims data (2013–2024). Used a prevalent new-user design matching individuals who added a GLP-1 RA to existing SGLT-2 inhibitor therapy with those continuing SGLT-2 inhibitors alone. Matching used hybrid exposure sets and time-conditional propensity scores. Cox proportional hazards models estimated hazard ratios for mortality and cardiovascular outcomes.

Who was studied

21,664 matched pairs of German adults with type 2 diabetes on SGLT-2 inhibitor therapy (nationwide insurance claims, 2013–2024)

What this study cannot tell us

Observational design means residual confounding cannot be fully excluded — patients prescribed combination therapy may be different from those on monotherapy in unmeasured ways. The median follow-up of 1.3 years is relatively short for mortality outcomes. The study uses claims data without access to lab values, imaging, or clinical notes.

How to read the evidence

This is a large, well-designed observational study using propensity score matching and multiple sensitivity analyses. While not a randomized trial, the sophisticated methodology and large sample size provide stronger evidence than typical observational studies. Rated moderate-high because residual confounding cannot be fully excluded.

When this study was published

Published in 2026 with follow-up through 2024, this is the most current large-scale real-world evidence on SGLT-2 + GLP-1 RA combination therapy outcomes.

The bigger picture

Diabetes treatment has shifted from focusing solely on blood sugar to prioritizing cardiovascular and kidney outcomes. Both SGLT-2 inhibitors and GLP-1 drugs have individually proven CV benefits, but evidence for combining them has been mostly extrapolated from separate trials. This study provides the largest real-world evidence to date that the combination is more than the sum of its parts — supporting a dual-mechanism approach to cardiometabolic protection.

Questions still open

Would a randomized controlled trial confirm the 29% mortality reduction seen with combination therapy?
Which specific SGLT-2 inhibitor + GLP-1 RA combination produces the best outcomes?
Are the benefits of combination therapy consistent across different levels of cardiovascular risk?

Common questions

Why combine SGLT-2 inhibitors with GLP-1 drugs instead of using one?

These two drug classes work through completely different mechanisms. SGLT-2 inhibitors help the kidneys remove excess sugar and have proven heart and kidney benefits. GLP-1 drugs mimic a gut hormone to improve insulin release and reduce appetite. This study suggests using both together provides significantly greater protection against death and cardiovascular events than either alone.

Should all diabetes patients take both types of drugs?

Not necessarily. This study focused on patients who were already on SGLT-2 inhibitors. Current guidelines recommend considering both drug classes for patients with type 2 diabetes who have or are at high risk for cardiovascular or kidney disease. Cost, side effects, and individual patient factors should guide the decision.

Read the original research

Comparative effectiveness of combination therapy with SGLT-2 inhibitors and GLP-1 RAs compared with SGLT-2 inhibitors in individuals with type 2 diabetes: A prevalent new-user cohort study.

Diabetes, obesity & metabolism

View on PubMed ↗Publisher’s paper ↗

Citation

Maier, Gregor A; Hennig, Beata; Rathmann, Wolfgang; Kuss, Oliver. (2026). Comparative effectiveness of combination therapy with SGLT-2 inhibitors and GLP-1 RAs compared with SGLT-2 inhibitors in individuals with type 2 diabetes: A prevalent new-user cohort study.. Diabetes, obesity & metabolism. https://doi.org/10.1111/dom.70523