ADA 2020: Dapagliflozin may help reduce onset of type 2 diabetes

A study presented at the American Diabetes Association's (ADA's) 80th Virtual Scientific Sessions – ‘Effect of Dapagliflozin on the Incidence of Diabetes: A Prespecified Exploratory Analysis from DAPA-HF’ has reported that the SGLT2 inhibitor dapagliflozin, when used in patients with heart failure, provided a benefit in preventing type 2 diabetes (T2D).

The original DAPA-HF trial was a phase 3 placebo-controlled international study of dapagliflozin in people with chronic heart failure and a reduced ejection fraction. The trial enrolled 4774 participants with a mean age of 66 years, both with and without type 2 diabetes, that were randomly assigned to take either 10 mg of dapagliflozin or a placebo once daily and were followed for 18.2 months. The study indicated the risk of worsening heart failure or death from cardiovascular causes was lower among the dapagliflozin patients than among those who received the placebo, regardless of the presence or absence of diabetes.

The current planned analysis assessed whether dapagliflozin reduced the incidence of T2D in the 2605 trial participants who did not have T2D when the study began. Of the participants without T2D, 1298 had been assigned to the dapagliflozin group, and 1307 to the placebo group. New-onset T2D was defined as A1C ≥ 6.5% on two consecutive study visits throughout the median 18.2-month follow-up.

The study showed that a total of 157 participants developed T2D, 150 of whom had prediabetes (A1C 5.7-6.4%) at the beginning of the study. Those who developed diabetes had higher mean HbA1c, greater body mass index (BMI) and lower eGFR at the beginning of the study than those who did not develop diabetes. Cox proportional hazards model data showed dapagliflozin reduced new-onset diabetes by 32%, with 4.9% of dapagliflozin patients (64 of 1298) developing T2D, compared to 7.1% (93 of 1307) in the placebo group. In an additional exploratory analysis, those patients who did develop diabetes during the trial experienced a 70% increase in mortality, after adjustments for baseline features.

To put into context – the risk reduction in developing diabetes here is comparable to the 31% reduction with metformin, as seen in the Diabetes Prevention Program. Further studies are needed to see if this observation can be extended to patients without heart failure and reduced ejection fraction, and to evaluate how durable the benefit might be or if the benefit persists after the discontinuation of therapy. It is also tempting to speculate that improvement in cardiac function among people with heart failure may precipitate improvement in glucose metabolism and insulin sensitivity by a variety of mechanism, including via improvement in muscle microvascular blood flow.