A combination therapy of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) may prevent major adverse cardiac and cerebrovascular events (MACCE) and heart failure (HF) in people with type 2 diabetes (T2D). These findings were published in Diabetes Care.

Data were sourced from the Clinical Practice Research Datalink (CPRD) GOLD, CPRD Aurum, and Secure Anonymised Information Linkage (SAIL) Databank repositories for this nested case-control study. Within each database, incident MACCE and HF events were assessed on the basis of antidiabetic drug use among patients with T2D. Each patient with T2D was matched with up to 20 healthy control participants.

Among 440,089 individuals with T2D, the unadjusted incidence of MACCE was 18.1 per 1000 person-years (py) and HF was 13.9 per 1000 py. Compared with controls, patients who had MACCE were more likely to be White, live in deprived areas, smoke, have diabetes-related microvascular complications, and several other comorbidities. Those with HF had similar characteristics were more likely to be older than the MAACE group but have the same comorbidities.

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Among the T2D cohort with MACCE (n=18,490), 3.2% used SGLT2i, 2.5% used GLP-1RAs, 0.3% used SGLT2i/GLP-1RAs combination therapy, and 26.5% used other combination therapies. In patients without prior cardiovascular disease, SGLT2i treatment was associated with decreased risk for MACEE compared with other combination therapies (adjusted odds ratio [aOR], 0.82; 95% CI, 0.73-0.92) as was SGLT2i/GLP-1RA combination therapy (aOR, 0.70; 95% CI, 0.50-0.98). Treatment with a GLP-1RA alone was not associated with a significantly lower odds of MAACE (aOR, 0.93, 95% CI, 0.81-1.06).

Among the T2D cohort with HF (n=17,428), 1.7% used SGLT2i regimens, 2.8% used GLP-1RA regimens, 0.2% used SGLT2i/GLP-1RA combination therapy, and 25.0% used other combination therapies. Compared with other combinations, SGLT2i (aOR, 0.49; 95% CI, 0.42-0.58), GLP-1RA (aOR, 0.82; 95% CI, 0.71-0.95), and SGLT2i/GLP-1RA combination (aOR, 0.43; 95% CI, 0.28-0.64) therapies were associated with decreased HF risk. The combination SGLT2i and GLP-1RA regimen was associated with a 57% lower odds of HF compared with other combination regimens.

The investigators acknowledged one of the limits of the study’s findings was the assessment of outcomes by drug classes and not by individual medications.

“SGLT2i and SGLT2i/GLP-1RA combination regimens may be beneficial in [the] primary prevention of MACCE and HF and GLP-1RA for HF,” the researchers concluded. “These data call for primary prevention trials using these agents and their combination.”

Disclosure: Some authors declared affiliations with pharmaceutical companies. . Please refer to the original reference for a full list of authors’ disclosures.


Wright AK, Carr MJ, Kontopantelis E, et al. Primary prevention of cardiovascular and heart failure events with SGLT2 inhibitors, GLP-1 receptor agonists, and their combination in type 2 diabetes. Diabetes Care. 2022;dc211113. doi:10.2337/dc21-1113