Incretin-based drugs were not linked to HF hospitalization compared with other oral antidiabetic drug combinations

Incretin-based drugs, including dipeptidyl peptidase-4 inhibitors and glucagon-like peptide 1 analogues, did not appear to be associated with greater heart failure (HF) hospitalization risk compared with commonly used combinations of oral antidiabetic drugs, according to a cohort study of 1.4 million patients. No association with HF hospitalization was found in patients with or without HF at baseline or when the 2 incretin-based drug classes were compared separately to other combination therapies.

The study was published in the March 24 New England Journal of Medicine and was summarized in the April ACP Diabetes Monthly. The following commentary by Donald A. Smith, MD, MPH, was published in the ACP Journal Club section of the July 19 Annals of Internal Medicine.

The increased risk for morbidity and mortality associated with congestive HF (CHF) in patients with diabetes may be underappreciated. CHF is a major cause of premature death in patients with diabetes. Although it is often caused by coronary heart disease or hypertension, CHF may also be independent of these 2 diagnoses and referred to as diabetic cardiomyopathy. In a study of Medicare claims, older patients with diabetes and incident CHF had higher mortality rates than those without CHF (33 vs. 3.7/100 patient-years). In addition, each 1% increase in HbA1c level has been associated with an 8% relative increase in incident CHF. Although glucose control has been shown to decrease incident myocardial infarction, it has not been shown to decrease CHF hospitalization or mortality. A recent meta-analysis of 14 trials assessing different glucose-lowering drugs or other strategies suggested that greater treatment-related weight gain was associated with greater risks for incident CHF.

The conceptually complex, nested case–control study of incretin-based drugs by Filion and colleagues might reassure us that these drugs do not increase CHF risk. However, although a large 3-year trial found no increased risk for HF hospitalization with sitagliptin vs. placebo, randomized trials found that saxagliptin increased HF hospitalizations, leading to a recent Food and Drug Administration warning about both saxagliptin and alogliptin. This illustrates why individual placebo-controlled trials of diabetes drugs and cardiovascular outcomes are needed for adequate safety assessment.

Clinicians should continue to focus on controlling lipids and hypertension to prevent coronary events that often precede CHF. In choosing methods to improve glucose control, one must take care not to use agents that promote CHF.