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Reduced new-onset T2D: Another benefit of dapagliflozin

Roshini Claire Anthony
23 Jul 2020

Dapagliflozin reduced the incidence of new-onset type 2 diabetes (T2D) in patients with heart failure and reduced ejection fraction (HFrEF), according to a prespecified exploratory analysis of the DAPA-HF* trial.

“While the major role of dapagliflozin is to reduce cardiovascular (CV) mortality and worsening of HF, decreasing incident diabetes could be considered an additional benefit,” said study author Professor Silvio E. Inzucchi from the Yale University School of Medicine and Yale Diabetes Center, New Haven, Connecticut, US, who presented the findings at ADA 2020.

“In this very high-risk population, the safety profile of dapagliflozin was excellent, the treatment well-tolerated with low discontinuation rates,” he added.

Of the 4,744 patients with HFrEF (NYHA class II–IV and LVEF** 40 percent) enrolled in the DAPA-HF trial, 55 percent (n=2,605) were without T2D at baseline (mean age 66.2 years, 75.7 percent male, mean BMI 27.2 kg/m2, mean HbA1c 5.8 percent). They were randomized to receive once-daily doses of dapagliflozin (10 mg) or placebo. Median follow-up was 18.2 months.

A total of 157 patients (6.0 percent) developed T2D, 95.5 percent of whom (n=150) had pre-diabetes at baseline (HbA1c 5.7–6.4 percent).

There was a 32 percent significant reduction in the incidence of new-onset T2D, defined as HbA1c 6.5 percent at two consecutive assessments or initiation of glucose-lowering medication, among those assigned to dapagliflozin vs placebo (4.9 percent vs 7.1 percent; hazard ratio [HR], 0.68, 95 percent confidence interval, 0.50–0.94; p=0.019). [ADA 2020, abstract 271-OR]

Compared with those who did not develop T2D, those who did had a higher baseline HbA1c (mean 6.2 vs 5.7; p<0.001), higher BMI (mean 28.5 vs 27.1 kg/m2; p=0.003), and lower estimated glomerular filtration rate (eGFR; mean 61.5 vs 68.2 mL/min/1.73 m2; p<0.001), with a greater proportion with eGFR <60 mL/min/1.73 m2 (48.4 percent vs 35.5 percent; p=0.001).

The effects of dapagliflozin in reducing new-onset T2D appeared greater among patients aged 65 vs >65 years (HR, 0.44 and 0.89, respectively; p=0.04) or with below vs above median NT-proBNP levels (HR, 0.42 and 1.02; p=0.01).

Exploratory analysis suggested an increased risk of all-cause mortality (HR, 1.70; p=0.035) and CV death (HR, 1.77; p=0.035) with new-onset T2D vs non-diabetics. 

Inzucchi noted that the findings only applied to patients with HFrEF, and that the lack of oral glucose tolerance testing or fasting plasma glucose assessments were limitations. “We will need to do more studies to see if this effect extends to patients without HFrEF and to evaluate how durable the benefit might be and how long diabetes prevention persists after the discontinuation of therapy.”

“DAPA-HF was the first trial to show the effectiveness of an SGLT2*** inhibitor (dapagliflozin) to improve clinical outcomes in patients with HFrEF with or without T2D,” pointed out Inzucchi. This was previously demonstrated with a reduction in a composite of CV death and worsening HF with dapagliflozin vs placebo (HR, 0.74; p=00001), a result consistent regardless of whether patients did or did not have T2D (HR, 0.75 and 0.73, respectively). [N Engl J Med 2019;38:1995-2008]

“DAPA-HF is [also] the first trial to demonstrate a “diabetes prevention” effect from an SGLT2 inhibitor,” he added. He noted that the minimal reduction in HbA1c with dapagliflozin in those without diabetes at baseline “may dispel concerns about merely masking the development of T2D.”

 

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Most Read Articles
Stephen Padilla, 22 Jul 2019
Zinc supplementation significantly lowers key glycaemic indicators, particularly fasting glucose (FG) in individuals with diabetes and in those who received an inorganic supplement, results of a systematic review and meta-analysis have shown.
Elaine Soliven, 15 Oct 2020

Higher levels of exercise appear to be associated with a lower risk of all-cause mortality in adults with type 2 diabetes (T2D) compared with no exercise at all, according to a study presented at EASD 2020.

Elvira Manzano, 07 Oct 2020
Exendin-4 imaging targeting GLP-1* receptor (GLP-1R) ably detects residual, dysfunctional pancreatic beta cells in individuals with long-standing type 1 diabetes (T1D), according to a study presented at EASD 2020. This breakthrough brings research closer to the possibility of restoring insulin-producing cells depleted in T1D.
Elaine Soliven, 4 days ago
Ultra rapid lispro (URLi) was noninferior to lispro in reducing HbA1c levels in adults with type 1 diabetes (T1D), according to the PRONTO-Pump-2* study presented at EASD 2020.