No rise in serious HF seen in patients taking saxagliptin or sitagliptin

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HF risks appear comparable

The findings of Toh et al. allay concerns about a saxagliptin- or sitagliptin-associated risk for heart failure. This risk was similar between the two agents and either comparable to or lower than that in all other comparator groups.

Beyond reassuring clinicians, this study illustrates the value of large, longitudinal databases built from clinical and administrative data, to complement the findings of clinical trials. These investigators were able to draw their conclusions from rich demographic, diagnostic, prescription, and utilization data based in routine real-world practice.

Joseph V. Selby, M.D., is at the Patient-Centered Outcomes Research Institute, Washington. He reported having no relevant financial disclosures. Dr. Selby made these remarks in an editorial accompanying Dr. Toh’s report (Ann. Intern. Med. 2016 April 25. doi:10.7326/M16-0869).




Neither saxagliptin nor sitagliptin, the two oral DPP-4 inhibitors most commonly used as antihyperglycemic medications, raised the risk of hospitalization for heart failure in a large population-based cohort study that analyzed data from a Food and Drug Administration surveillance program.

The report was published online April 25 in Annals of Internal Medicine.

The cardiovascular safety of DPP-4 inhibitors is controversial: Several postmarketing studies have produced conflicting results, particularly with regard to HF risk. “Patients with diabetes have a higher HF risk than those without, so any antihyperglycemic agent that modifies the risk warrants further examination,” said Sengwee Toh, Sc.D., a pharmacoepidemiologist in the department of population medicine, Harvard Medical School and Harvard Pilgrim Health Institute, Boston, and his associates.

They compared rates of HF among demographically and geographically diverse patients who initiated antidiabetic medications during a 7-year period in routine clinical settings. The study population included 78,553 adults who initiated saxagliptin and 298,124 who initiated sitagliptin, who were compared with patients who initiated pioglitazone, second-generation sulfonylureas, or long-acting insulins. Mean follow-up was 7-9 months.

There was no evidence of an increased risk of hospitalization for HF among new users of saxagliptin or sitagliptin. The hazard ratios for developing HF were 0.83 for saxagliptin vs. sitagliptin, 0.63 for saxagliptin vs. pioglitazone, 0.69 for saxagliptin vs. sulfonylureas, and 0.61 for saxagliptin vs. insulin. Similarly, the hazard ratios for developing HF were 0.74 for sitagliptin vs. pioglitazone, 0.86 for sitagliptin vs. sulfonylureas, and 0.71 for sitagliptin vs. insulin.

These results were consistent across sensitivity analyses and subgroup analyses that categorized patients by whether or not they had preexisting cardiovascular disease and whether or not they had a history of prior HF, the investigators said (Ann Intern Med. 2016 April 25. doi:10.7326/M15-2568).

However, this was an observational study with a relatively short follow-up. “Well-designed randomized trials with hospitalization for HF as the main endpoint or observational studies that address the limitations of our study will help provide more definitive evidence on the topic,” Dr. Toh and his associates said.

This study was supported by the FDA. Dr. Toh reported having no relevant financial disclosures; one of his associates reported receiving personal fees from Novartis unrelated to this work.

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