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Dapagliflozin improves glycemic control, weight, BP in patients with type 2 diabetes, HF
Adults with concomitant type 2 diabetes and heart failure assigned dapagliflozin therapy saw reduced HbA1c, body weight and systolic blood pressure vs. those assigned placebo, according to a pooled, post-hoc analysis of completed clinical trials.
“There is a substantial need for glucose-lowering therapies that have proven safety and which may have beneficial effects on HF outcomes in patients with concomitant diabetes and HF — a growing and highly complex group that currently experiences high rates of hospitalizations and substantial symptom burden,” Mikhail Kosiborod, MD, of the department of cardiology at Saint Luke’s Mid America Heart Institute in Kansas City, Missouri, and colleagues wrote. “The majority of the currently available options for [type 2 diabetes] management have not been specifically tested for safety and efficacy in patients with established HF. Furthermore, several existing classes of glucose-lowering medications present potential safety issues, specifically in terms of volume overload and hospitalizations for HF.”
Kosiborod and colleagues analyzed data from five clinical trials (one phase 2b/3 and four phase 3 studies) involving patients with type 2 diabetes and a history of HF randomly assigned 10 mg dapagliflozin (n = 171; Farxiga, AstraZeneca) or placebo (n = 149; mean age, 64 years; mean diabetes duration, 14 years; mean HbA1c, 8.2%; 50% with New York Heart Association class II/III HF). Researchers assessed HbA1c, weight and systolic BP (two studies) up to 52 weeks, using longitudinal repeated-measures models, as well as composite cardiovascular outcomes, hospitalizations for HF and adverse events.
At 52 weeks, patients assigned dapagliflozin therapy had greater reductions in HbA1c (mean placebo-adjusted reduction, –0.55%; 95% CI, –0.8 to –0.3), body weight (mean placebo-adjusted reduction, –2.67 kg; 95% CI, –3.88 to –1.47) and systolic BP (mean placebo-adjusted reduction, –2.05 mm Hg; 95% CI, –5.68 to 1.57) vs. placebo.
Hospitalization for HF was rare, but numerically lower in the dapagliflozin group vs. placebo (1 vs. 7) for an HR of 0.14 (95% CI, 0-1.2), according to researchers.
The point estimate of HRs for composite CV outcomes, hospitalization for HF and major adverse cardiac events favored dapagliflozin vs. placebo. No between-group differences were observed for serious adverse events, which included cardiac, gastrointestinal, musculoskeletal and nervous system disorders. There was one death in the placebo group. Additionally, no between-group differences were observed for volume reduction events, an adverse event of special interest.
“Variability in change in [systolic BP] was observed in both treatment arms in our analysis, which may be attributed to the fact that many patients had a change in medications affecting [BP] and data after such a change was excluded,” the researchers wrote. “However, while changes in [systolic BP] were less consistent, they numerically favored dapagliflozin vs. placebo at most time points. In addition, the trend toward a decrease in [systolic BP] seen with dapagliflozin occurred without an increase in heart rate; an observation previously reported with SGLT2 inhibitors in other patient populations.” – by Regina Schaffer
Disclosure: AstraZeneca supported this study. Kosiborod reports receiving consultant honoraria or research support or serving on advisory panels for AstraZeneca, Amgen, Boehringer Ingelheim, Eli Lilly, Genentech, Gilead Sciences, GlaxoSmithKline, Glytec, Merck, Novo Nordisk, Sanofi Aventis, Takeda and ZS Pharma. All other researchers are employees and shareholders of AstraZeneca.