Dapagliflozin Use Could Reduce Risk of Developing Type 2 Diabetes

A new analysis of nondiabetic patients from the landmark DAPA-HF trial suggests use of dapagliflozin could slash the incidence rate of diabetes by almost a third.

Using the 55% of DAPA-HF participants without diabetes at baseline, results of the analysis, which was presented at the American Diabetes Association’s (ADA) 80th Scientific Sessions, indicates nondiabetics patients receiving dapagliflozin reduced the rate of new-onset diabetes by 32% compared to patients receiving placebo.

“We took this opportunity because they were going to be randomized to placebo or dapagliflozin to see if dapagliflozin had any specific benefit in preventing those patients from developing diabetes,” said study presenter Silvio Inzucchi, MD, clinical chief of the Section of Endocrinology and medical director of the Yale Diabetes Center, in an interview with HCPLive.

Designed as a prespecified exploratory analysis, investigators hoped to assess the rate of new-onset type 2 diabetes in patients with heart failure with reduced ejection fraction (HFrEF). Using data from study, investigators identified 2605 patients with a median of 18.2 months of follow-up for inclusion in their study.

For the purpose of their analysis, investigators defined new-onset type 2 diabetes as an HbA1c level of 6.5% or greater at 2 consecutive study visits post-randomization or the administration of a new glucose-lowering agent.

Of the 2605 nondiabetics identified for inclusion, 157 developed type 2 diabetes during the trial, of which 150 were classified as having prediabetes at baseline. Compared to those who did not develop type 2 diabetes, those with incident type 2 diabetes had a higher mean baseline HbA1c (6.2±0.3% vs 5.7±0.4%; P <.001), greater BMI (28.5±5.9 vs 27.1±5.7 kg/m2; P=.003), and lower eGFR (61.5±17.4 vs 68.2±19.3 ml/min/1.73 m2; P <.001) at baseline.

Using a Cox proportional hazards model, investigators determined those receiving dapagliflozin reduced risk of new-onset diabetes by 32% (HR, 0.68; 95% CI, 0.50-0.94; P=.019) compared to those receiving placebo. Specifically, 93 of 1307 (7.1%) in the placebo group developed type 2 diabetes compared to 64 of 1298 in the dapagliflozin groups. Investigators highlighted these results were confirmed using a Fine and Gray competing risk model.

For a better understanding of the potential mechanism behind dapagliflozin and what this latest data adds to the excitement surrounding the agent and SGLT2 class as a whole, HCPLive caught up with Inzucchi and that conversation is the subject of a special edition ADA 2020 House Call.

This study, “Effect of Dapagliflozin on the Incidence of Diabetes: A Prespecified Exploratory Analysis from DAPA-HF,” was presented at ADA 2020.