- Results from TECOS, which included more than 14,000 patients, showed no increased risk of heart problems, including cardiovascular (CVD) death, heart attack, stroke or hospitalization for chest pain, among patients who took Merck's mega-blockbuster diabetes drug Januvia (sitagliptin).
- Januvia is part of a class of hypoglycemic drugs known as DPP-4 inhibitors. Januvia became the first FDA-approved DPP-4 inhibitor in 2006.
- Previous studies, including the SAVOR study, have shown a link between certain DPP-4 inhibitors and increased risk of hospitalization for heart failure.
Not all DPP-4 inhibitors are created alike, at least according to the safety data from two large-scale trials—SAVOR and TECOS. In the SAVOR trial, the DPP-4 inhibitor, Onglyza (saxagliptin) from AstraZeneca, was associated with a 27% increased risk of being hospitalized with heart failure. In a different trial, EXAMINE, Nesina (alogliptin), a DPP-4 inhibitor from Takeda, was associated with a slightly elevated heart failure risk, though the results were not deemed significant. (CORRECTION: In a previous version of this post, we misstated the name of the Nesina trial).
It should be noted, however, that despite the lack of increased heart failure risk, Januvia is associated with a 0.1% increased risk of acute pancreatitis—a small risk to be sure, but still a risk. As for Nesina and Onglyza, both drugs are associated with a 0.2% increased risk of acute pancreatitis.
It's clear that some of the CVD safety issues that have arisen with Onglyza are not a class effect; but overall, DPP-4 inhibitors are an important part of the treatment armamentarium for type 2 diabetes—especially in terms of long-term control of glycosolated hemoglobin (A1C).
A meta-analysis of 19 studies has shown that taking a DPP-4 inhibitor can decrease A1C levels by an average of 0.74%—and as much as 1.2%—for long periods of time. For this reason, many physicians have determined that the benefits outweigh the risks, and DPP-4 inhibitors continue to be a go-to therapy for treating patients with type 2 diabetes.