No significant protective effect against stroke was found with the use of DPP-IV inhibitors, according to results from a meta-analysis.
“[Type 2 diabetes] is undoubtedly associated with an increased risk of microvascular complications, such as retinopathy, nephropathy and neuropathy,” the researchers wrote. “However, macrovascular complications are the primary cause of death in such patients, with acute ischemic myocardial infarction and stroke accounting for 80% of deaths in diabetes individuals. Despite the development of insulin as well as other agents to improve glycemic control in diabetes patients, there is considerable debate over whether these treatment modalities can lower the risk of major cardiovascular disease outcomes, including stroke.”
H. J. Milionis, MD, PhD, of the department of internal medicine at the School of Medicine, University of Ioannina in Greece, and colleagues conducted a meta-analysis of 22 studies to determine the risk for stroke in individuals prescribed DPP-IV inhibitors.
The studies included 19 small prospective studies evaluating the efficacy and safety of gliptins and three large-scale randomized controlled trials evaluating CV outcomes as the primary endpoint.
The DPP-IV inhibitors evaluated were saxagliptin (Onglyza, AstraZeneca), alogliptin (Nesina, Takeda), vildagliptin, sitagliptin (Januvia, Merck) and linagliptin (Tradjenta, Boehringer Ingelheim).
Researchers found a slight benefit of DPP-IV inhibitors against stroke in evaluation of the prospective studies, but the trend was not significant compared with placebo (OR = 0.639; 95% CI, 0.336-1.212).
Evaluation of the large-scale trials revealed no differences in the risk for stroke with DPP-IV inhibitors compared with placebo (OR = 0.996; 95% CI, 0.85-1.166).
“Our analyses of the available data from small prospective studies found a nonsignificant trend toward a benefit for diabetes patients taking gliptins against ischemic stroke incidence over placebo,” the researchers wrote. “This finding is in line with evidence from preclinical studies, which demonstrated neuroprotective actions of DPP-IV inhibitors in experimental models of ischemic stroke. However, our analysis of the data derived from the three large [randomized controlled trials] showed that, in the long term, treatment with these agents actually had neutral effects on the risk of stroke.” – by Amber Cox
Disclosure: Milionis reports having given talks, attended conferences and participated in trials and advisory boards sponsored by various pharmaceutical companies.