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Am Fam Physician. 2021;104(4):424

Clinical Question

For patients with type 2 diabetes mellitus who are taking a glucagon-like peptide-1 (GLP-1) receptor agonist, is a sodium-glucose cotransporter 2 (SGLT2) inhibitor or a sulfonylurea preferred if an additional drug is needed?

Bottom Line

This propensity score–matched analysis (not funded by industry) concluded that an SGLT2 inhibitor is preferred over a sulfonylurea for patients with type 2 diabetes who are already taking a GLP-1 receptor agonist, with favorable effects on the likelihood of hospitalization for myocardial infarction and heart failure, and all-cause mortality. (Level of Evidence = 2b)


There have been no randomized trials that address whether there are benefits to adding an SGLT2 inhibitor or sulfonylurea in patients with type 2 diabetes who are already taking a GLP-1 receptor agonist. The researchers used three U.S. insurance registries to identify adults with type 2 diabetes who were taking a GLP-1 receptor agonist and had not taken an SGLT2 inhibitor or a sulfonylurea in the previous three months. Patients with gestational or type 1 diabetes, cancer, end-stage renal disease, or HIV infection were excluded. After initially identifying 32,221 patients adding an SGLT2 inhibitor and 26,894 adding a sulfonylurea, the authors used propensity score matching with more than 95 covariates to create 12,584 matched pairs for comparison. Patients were followed up for a mean of 10 months. The primary outcome was a composite of hospitalization for myocardial infarction and stroke, and all-cause mortality. A secondary outcome was hospitalization for heart failure. The primary outcome was significantly less likely in the group given an SGLT2 inhibitor (9.9 vs. 13.0 events per 1,000 person-years; adjusted hazard ratio [HR] = 0.76; 95% CI, 0.59 to 0.98; number needed to treat = 322 per year to prevent one event). Heart failure hospitalizations were also less common in the group given an SGLT2 inhibitor (13.0 vs. 20.8 per 1,000 person-years; adjusted HR = 0.64; 95% CI, 0.50 to 0.82; number needed to treat = 128 per year to prevent one hospitalization). The reduction in the composite outcome was driven primarily by reductions in myocardial infarction (adjusted HR = 0.71; 95% CI, 0.51 to 1.003) and all-cause mortality (adjusted HR = 0.68; 95% CI, 0.40 to 1.14), but not for stroke (adjusted HR = 1.05; 95% CI, 0.62 to 1.79).

Study design: Randomized controlled trial (single-blinded)

Funding source: Industry and government

Setting: Emergency department

Reference: Dave CV, Kim SC, Goldfine AB, et al. Risk of cardiovascular outcomes in patients with type 2 diabetes after addition of SGLT2 inhibitors versus sulfonylureas to baseline GLP-1RA therapy [published correction appears in Circulation. 2021;143(8):e744]. Circulation. 2021;143(8):770–779.

Editor's Note: Dr. Ebell is deputy editor for evidence-based medicine for AFP and cofounder and editor-in-chief of Essential Evidence Plus, published by Wiley-Blackwell.

POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see Copyright Wiley-Blackwell. Used with permission.

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