Clinicians should think twice before prescribing DPP-4 inhibitors for diabetes

While reviewing abstracts in my role as an Evidence Based Medicine editor, I recently encountered a seemingly strange randomised trial of sitagliptin, one of the new dipeptidyl peptidase-4 (DPP-4) inhibitor antidiabetic drugs. Appearing in the New England Journal of Medicine , the trial evaluated the impact of sitagliptin on cardiovascular outcomes in patients with non-ideally controlled type 2 diabetes with established cardiovascular disease, concluding that sitagliptin was both non-inferior and non-superior to placebo in this high-risk group.1 As a primary care physician, my hope for diabetic patients of mine is that a new medication, such as sitagliptin, would be superior to placebo in reducing their high cardiovascular risk. However, in this high-risk population with prevalent cardiovascular disease, sitagliptin seemed to have no impact on cardiovascular outcomes over the median 3-year follow-up of the trial, so the clinical implications of the findings for my patients seemed dubious. I wondered why a trial demonstrating the non-inferiority of sitagliptin to placebo merited appearance in the world's highest impact general medical journal. Of course, a trial such as this—the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS)—has a broader audience than front-line physicians. Indeed, on closer inspection, one suspects that …