Spotlight on potential risks of DPP-4 inhibitors

Dipeptidyl peptidase-4 (DPP-4) inhibitors were examined for potential associations with heart failure, pancreatic cancer, and fractures in recent studies.

Patients with known cardiovascular disease taking DPP-4 inhibitors may have an increased risk of hospitalization for heart failure, according to a meta-analysis published by The BMJ on Feb. 17. Moderate-quality evidence from 5 controlled trials showed an odds ratio (OR) for hospitalization of 1.13 (95% CI, 1.00 to 1.26) in patients taking the drugs, and a similar trend was found in the observational studies but with very low-quality evidence. Pooling of 38 trials reporting on heart failure provided low-quality evidence that DPP-4 inhibitors were not associated with any increased risk of heart failure, the analysis also found. A strength of this study was that it separately analyzed heart failure and hospitalization for heart failure, the authors noted. They concluded that the “relative effect of DPP-4 inhibitors on heart failure remains uncertain” and suggested that clinicians and patients consider the risk for heart failure hospitalization when choosing a diabetes drug for patients with existing cardiovascular disease.

More reassuring findings were offered by a study of pancreatic cancer risk, also published by The BMJ the same day. Almost a million new users of diabetes drugs were followed for a median of 1.3 to 2.8 years. Compared to sulfonylureas, incretin-based drugs (most patients were taking DPP-4 inhibitors, but glucagon-like peptide-1 receptor agonists were also included) were not associated with any increased risk for pancreatic cancer (pooled adjusted hazard ratio, 1.02; 95% CI, 0.84 to 1.23). Pancreatic cancer risk will need to be reassessed when the drugs have been on the market longer, but “these findings provide some reassurance on the safety of incretin based drugs,” the study authors said. An accompanying editorial noted that the information from this study and the heart failure study will be further supplemented by a forthcoming report from the Agency for Healthcare Research and Quality on diabetes drug risks and benefits.

Another study, looking specifically at sitagliptin, found no association between the drug and osteoporotic fractures. It included 8,894 new users of sitagliptin and 63,934 nonusers, all with type 2 diabetes. The sitagliptin group had 4.8 fractures per 1,000 person-years versus 4.0 per 1,000 person-years in nonusers (P=0.3). Although multivariable analysis found no association between sitagliptin and fractures, significant associations were observed with fractures for other drug classes, including insulin (P<0.001), sulfonylureas (P<0.001), and thiazolidinediones (P=0.019). The study authors conclude by suggesting the study results be considered in treatment decisions for patients with type 2 diabetes and high risk of fracture. The study was published by the Journal of Clinical Endocrinology and Metabolism on March 1.