Patient-Oriented Evidence That Matters

SGLT2 Inhibitors or GLP-1 Receptor Agonists Reduce Cardiovascular Outcomes in Patients with Type 2 Diabetes


Am Fam Physician. 2021 Aug ;104(2):206.

Clinical Question

Do sodium-glucose cotransporter 2 (SGLT2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists reduce patient-oriented outcomes in patients with type 2 diabetes mellitus?

Bottom Line

SGLT2 inhibitors, the diabetes medications ending in -flozin (such as dapagliflozin [Farxiga]), and GLP-1 receptor agonists, the -tide medications (such as dulaglutide [Trulicity]), decrease cardiovascular and renal outcomes to a greater extent than placebo or other treatments. They should be considered in addition to metformin and other glucose-lowering treatments for most patients with type 2 diabetes. (Level of Evidence = 1a)


The researchers searched three databases, including Cochrane CENTRAL, to identify randomized trials that compared SGLT2 inhibitors or GLP-1 receptor agonists with other treatment approaches. Two researchers independently screened studies for inclusion, extracted the data, and assessed the studies for risk of bias. Because there are a handful of drugs in each class that have not been directly compared with one another, the researchers completed a network meta-analysis, which combines direct and indirect evidence across studies to allow cross-comparison. They identified 764 trials including 421,346 patients, which allowed a view of the results according to patient baseline cardiovascular risk. The quality of the studies was generally high, with no heterogeneity for most outcomes. Both drug classes lowered all-cause mortality, cardiovascular mortality, nonfatal myocardial infarction, and kidney failure. SGLT2 inhibitors were more effective at reducing hospital admission, and GLP-1 receptor agonists were more likely to reduce nonfatal stroke. The absolute benefit of treatment varied based on underlying cardiac risk; for example, two to five fewer deaths per 1,000 patients over five years in patients at low risk and 24 to 48 fewer deaths per 1,000 patients at high risk. A calculator is available (https://magicevidence.org/match-it/200

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.

To subscribe to a free podcast of these and other POEMs that appear in AFP, search in iTunes for “POEM of the Week” or go to http://goo.gl/3niWXb.

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.



Want to use this article elsewhere? Get Permissions

CME Quiz

More in AFP

Editor's Collections

Related Content


May 2022

Access the latest issue of American Family Physician

Read the Issue

Email Alerts

Don't miss a single issue. Sign up for the free AFP email table of contents.

Sign Up Now

Navigate this Article