WASHINGTON, DC—Dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose co-transporter 2 (SGLT-2) inhibitors all displayed favorable cardiovascular (CV) safety profiles, according to a network meta-analysis presented at the ACC.17 Scientific Session by First Affiliated Hospital researchers, from Guangzhou, China.

It is still not clear what the benefits and risks for CV outcomes are for choosing one antidiabetic drug over another. Lead study author, Xiaodong Zhuang, and colleagues conducted a network meta-analysis to compare the effects on CV outcomes among 3 major antidiabetic drug classes: DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors. They first searched various electronic databases for randomized controlled trials comparing novel antidiabetics with other comparators in adults with type 2 diabetes.

Primary outcomes were major adverse cardiovascular events (MACEs), reported as odds ratios (OR) with 95% confidence intervals (CI). A separate correlation analysis of severe hypoglycemia and MACEs according to the ranking order was conducted. A total of 149 trials involving 145,884 patients were identified. 

“No single antidiabetic drug was significantly better than placebo for MACEs,” said Zhuang. 

Sulfonylureas (OR 1.28, 95% CI: 0.60–2.73) were ranked the lowest in terms of CV outcomes and SGLT-2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors were all significantly better than sulfonylureas. Empagliflozin, lixisenatide, exenatide, canagliflozin, sitagliptin, and vildagliptin were significantly better than sulfonylureas. 

Sulfonylureas were also associated with the highest risk of severe hypoglycemia (OR 6.75, 95% CI: 1.39–32.72). “Ranking order of MACEs risk was positively correlated with the ranking order of severe hypoglycemia risk both by class (P=0.002) and by individual (P=0.001),” added Zhuang.

The highest risk of MACEs seen with sulfonylureas may be explained by its increase in the risk of severe hypoglycemia. Study authors noted that these study results should be considered in healthcare policy making and in the development of clinical practice guidelines.