BOSTON — Dapagliflozin may significantly benefit patients with type 2 diabetes and cardiovascular disease (CVD) by improving a variety of risk factors when taken over the long term, according to a new study presented at the American Diabetes Association (ADA) 75th Scientific Sessions.  

“We know that patients with type 2 diabetes have increased comorbidities, such as obesity and hypertension, as well as a two-fold higher risk for cardiovascular disease. We also recognize that lowering body weight and reducing high blood pressure are associated with reductions in cardiovascular disease, while chronic hyperglycemia is a risk factor for developing cardiovascular disease,” William T. Cefalu, MD, editor-in-chief of Diabetes Care and executive director of the Pennington Biomedical Research Center in Baton Rouge, Louisiana, said at the conference.

During his presentation, Cefalu also noted that dapagliflozin is known to reduce hyperglycemia and renal glucose reabsorption while also increasing urinary glucose excretion.

Cefalu and colleagues evaluated data from two phase 3 studies — an original 52-week study followed by a 52-week extension study — conducted in patients with type 2 diabetes and pre-existing CVD. Patients were treated with dapagliflozin 10 mg daily (n=284) or placebo (n=284), and all those included in this pooled analysis entered the 2-year follow-up study period.

In terms of baseline characteristics, including CVD characteristics, both study groups were similar, and demographics were similar for those who started the study and those who entered the extension study.

Average was 62 to 63 years; about 74% to 79% had coronary heart disease (CHD); and about 10% to 13% had some degree of renal insufficiency.

Most patients were on multiple medications, including antidiabetic medications and insulin, with 41% to 44% in both studies being treated with insulin or oral agents and about 40% being treated with at least two oral therapies in both studies, Cefalu said.

At 104 weeks, compared with patients receiving placebo, those receiving dapagliflozin experienced a greater reduction in HbA1c (–0.35%), body weight (–3.16 kg) and systolic BP (–2.03 mm Hg), according to the data.

The researchers also assessed patients using a prespecified three-item composite endpoint comprised of an absolute drop in HbA1c of at least 0.5%, a relative drop in body weight of at least 3.5% and an absolute drop of 3 mm Hg in seated systolic BP.

Results showed that more patients in the dapagliflozin group vs. the placebo group met this endpoint from week 24 (9.5% vs. 2.1%, respectively) to week 52 (10.9% vs. 3.5%, respectively) and week 104 (6.7% vs. 1.4%, respectively).

Despite these positive results, one question that the researchers primarily wanted to address was safety of dapagliflozin over 2 years, according to Cefalu.

“What was consistent and maintained was the frequency of hypoglycemia, which compares very favorably with placebo,” Cefalu said, noting that there were no significant differences between those receiving dapagliflozin and those receiving placebo.

The researchers also observed no significant differences between the two groups in terms of renal impairment or renal failure and volume depletion.

However, a greater percentage of patients in the dapagliflozin group vs. the placebo group experienced genital infections (6.7% vs. 0.4%, respectively) and urinary tract infections (9.2% vs. 6.3%, respectively).

“In this particular extension trial, dapagliflozin was generally well tolerated in this cohort of patients with type 2 diabetes and pre-existing CVD at 104 weeks. Rates of hypoglycemia were similar between dapagliflozin and placebo, and events of volume depletion were equally balanced between treatment groups. Genital and urinary tract infections were more frequently observed with dapagliflozin vs. placebo. There was also no evidence of declining renal function observed over time with dapagliflozin,” Cefalu concluded.

Reference

  1. Cefalu WT et al. Abstract 106-OR: Long-Term Safety and Efficacy of Dapagliflozin in Patients with T2DM and Cardiovascular Disease. Presented at: American Diabetes Association (ADA) 75th Scientific Sessions; June 5-9, 2015; Boston.