SGLT-2 Inhibitors, GLP-1 Agonists Provide Greater Benefit for Patients With Type 2 Diabetes

What new treatments for patients with type 2 diabetes affect mortality and cardiovascular and renal outcomes?

In people with type 2 diabetes, sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) agonists outperform dipeptidyl-peptidase-4 (DPP-4) inhibitors and long-acting insulins as monotherapy or combination therapy, reducing all-cause mortality, major cardiovascular events, chronic kidney disease, and heart failure. SGLT-2 inhibitors and GLP-1 agonists are also less likely to cause severe hypoglycemia. (Level of Evidence = 1a)

The authors searched four databases and identified 84 randomized studies of the effect of SGLT-2 inhibitors, GLP-1 agonists, DPP-4 inhibitors, and long-acting insulins as monotherapy or combination therapy in adults with type 2 diabetes. These were large studies of middle-aged adults with long-standing (mean = 8.8 years) type 2 diabetes and comorbidities, such as hypertension or tobacco use, who were evaluated for a mean of almost 2 years. Data were abstracted by one investigator and verified by a second, and two reviewers independently assessed the risk of bias. The authors used direct and indirect comparisons of the treatments via network meta-analysis. Based on high-certainty evidence, SGLT-2 inhibitors and GLP-1 agonists reduced all-cause mortality and major adverse cardiovascular events compared with usual care. SGLT-2 inhibitors reduced the progression of chronic kidney disease and heart failure hospitalizations, and GLP-1 agonists reduced stroke. SGLT-2 inhibitors and GLP-1 agonists outperformed insulin regarding all-cause mortality. Long-acting insulins and DPP-4 inhibitors are not more effective than usual care to prevent bad outcomes. The risk of severe hypoglycemia is also lower with SGLT-2 inhibitors and GLP-1 agonists.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Self-funded or unfunded

Setting: Various (meta-analysis)

Reference: Drake T, Landsteiner A, Langsetmo L, et al. Newer pharmacologic treatments in adults with type 2 diabetes: a systematic review and network meta-analysis for the American College of Physicians. Ann Intern Med. 2024;177(5):618-632.

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