Glucagon-like peptide-1 receptor agonists versus sodium-glucose cotransporter-2 inhibitors in adults with type 2 diabetes and atrial fibrillation: a multicenter comparative effectiveness cohort study of cardiovascular and arrhythmic outcomes.
Islam M & Okere A • Diabetes research and clinical practice • 2026
GLP-1RA initiation was associated with lower risks of mortality, hospitalization, atherosclerotic events, and adverse AF disease-course outcomes than SGLT-2i in adults with concurrent AF and T2D over one year.
Key Findings
Results
GLP-1RA use was associated with significantly lower all-cause mortality compared to SGLT-2i use in adults with concurrent AF and type 2 diabetes.
HR 0.64 (95% CI 0.57–0.71) at 365 days
After 1:1 propensity-score matching, 18,035 GLP-1RA users were compared with 18,035 SGLT-2i users
Mean age of cohort was 67.4 years; 52.2% male, 47.8% female
E-values ranged 1.5–2.5, quantifying robustness to unmeasured confounding
The Benjamini-Hochberg procedure was used to control the false discovery rate
Results
GLP-1RA use was associated with lower risk of hospitalization compared to SGLT-2i use.
HR 0.88 (95% CI 0.84–0.92) at 365 days
Study used a new-user, active-comparator design from the TriNetX Research Network (2016–2024)
Patients were matched on demographic, clinical, laboratory, and medication covariates
Cox proportional hazards regression was used to estimate hazard ratios
Results
GLP-1RA use was associated with lower risk of 3-point major adverse cardiovascular events (MACE) compared to SGLT-2i use.
HR 0.78 (95% CI 0.71–0.86) at 365 days
3-point MACE is a composite endpoint typically including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke
Effects were consistent across age and body mass index subgroups
Results
GLP-1RA use was associated with lower risk of atrial fibrillation progression compared to SGLT-2i use.
HR 0.94 (95% CI 0.90–0.98) at 365 days
AF progression was one of the pre-specified AF disease-course outcomes
Results were consistent across age and BMI subgroups
Results
GLP-1RA use was associated with lower rates of AF ablation and cardioversion compared to SGLT-2i use.
AF ablation: HR 0.81 (95% CI 0.70–0.94) at 365 days
Cardioversion: HR 0.79 (95% CI 0.70–0.90) at 365 days
These outcomes represent procedural interventions reflecting adverse AF disease-course progression
E-values ranged 1.5–2.5 across outcomes, indicating moderate robustness to unmeasured confounding
Conclusions
The established benefits of SGLT-2i for heart failure and chronic kidney disease (CKD) were acknowledged as remaining the basis for class choice in those subpopulations.
The study design was a retrospective comparative effectiveness cohort study, not a randomized controlled trial
The authors note that SGLT-2i advantages for heart failure and CKD subpopulations were not negated by these findings
The study period was 2016–2024 using the TriNetX Research Network, a multicenter database
Methods
The study cohort comprised 36,070 propensity-score-matched adults with concurrent atrial fibrillation and type 2 diabetes drawn from a multicenter database.
18,035 GLP-1RA users matched 1:1 to 18,035 SGLT-2i users
Mean age was 67.4 years
Sex distribution was 52.2% male and 47.8% female
Matching was performed on demographic, clinical, laboratory, and medication covariates
Data source was the TriNetX Research Network covering 2016–2024
What This Means
This research compared two classes of diabetes medications—GLP-1 receptor agonists (such as semaglutide or liraglutide) and SGLT-2 inhibitors (such as empagliflozin or dapagliflozin)—in over 36,000 adults who had both type 2 diabetes and atrial fibrillation (an irregular heart rhythm). Using medical records from a large multicenter U.S. database spanning 2016 to 2024, researchers statistically matched patients in the two groups to make them as similar as possible, then tracked outcomes over one year. They found that patients who started GLP-1 receptor agonists had meaningfully lower rates of death, hospitalization, major cardiovascular events (such as heart attack and stroke), and atrial fibrillation-related procedures (such as ablation and cardioversion) compared to those who started SGLT-2 inhibitors.
The differences were notable: GLP-1RA users had a 36% lower risk of dying, a 22% lower risk of major cardiovascular events, and a 21% lower risk of needing cardioversion during the one-year follow-up. These advantages held up across different age groups and body weights. The researchers also tested how robust their findings were to potential hidden confounding factors (variables they couldn't measure), and found moderate but not exceptional robustness, meaning unmeasured differences between the groups could still partially explain the results.
This research suggests that for people living with both type 2 diabetes and atrial fibrillation, GLP-1 receptor agonists may offer broader cardiovascular and heart rhythm-related benefits compared to SGLT-2 inhibitors over a one-year period. However, the authors note that SGLT-2 inhibitors still have well-established advantages for people who also have heart failure or kidney disease, and those benefits should continue to guide treatment decisions in those specific patient groups. Because this was an observational study and not a randomized controlled trial, these findings should be interpreted with caution and ideally confirmed in future prospective research.
Islam M, Okere A. (2026). Glucagon-like peptide-1 receptor agonists versus sodium-glucose cotransporter-2 inhibitors in adults with type 2 diabetes and atrial fibrillation: a multicenter comparative effectiveness cohort study of cardiovascular and arrhythmic outcomes.. Diabetes research and clinical practice. https://doi.org/10.1016/j.diabres.2026.113346