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)

Synopsis

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/200820dist/#!/) that estimates benefit at various risk levels.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Self-funded or unfunded

Setting: Various (meta-analysis)

Reference: PalmerSC, Tendal B, Mustafa RA, et al. Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials. BMJ. 2021;372:m4573.

Editor's Note: Dr. Shaughnessy is an assistant medical editor for AFP.