Patient-Oriented Evidence That Matters

For Patients with Type 2 Diabetes Mellitus Who Are Taking a GLP-1 Receptor Agonist, an SGLT2 Inhibitor May Be Preferred to a Sulfonylurea as Add-on Therapy


Am Fam Physician. 2021 Oct ;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;

Athens, Ga.

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 http://www.essentialevidenceplus.com. Copyright Wiley-Blackwell. Used with permission.

For definitions of levels of evidence used in POEMs, see http://www.essentialevidenceplus.com/product/ebm_loe.cfm?show=oxford.

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This series is coordinated by Sumi Sexton, MD, editor-in-chief.

A collection of POEMs published in AFP is available at https://www.aafp.org/afp/poems.



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