medwireNews: The selective sodium-glucose cotransporter (SGLT)2 inhibitor bexagliflozin significantly lowers glycated hemoglobin (HbA1c), weight, and blood pressure relative to placebo in people with type 2 diabetes at high risk for cardiovascular (CV) events, phase 3 study findings show.
The data, presented at the virtual ADA 80th Scientific Sessions, also showed that the drug was noninferior to placebo when considering the composite CV safety endpoint of major CV events (CV death, myocardial infarction, stroke) plus unstable angina, which occurred in 7.9% of patients on bexagliflozin and 10.1% of those on placebo.
The international BEST study included 1700 individuals (30% women) with type 2 diabetes who were aged 40 years and older (mean 64 years), with an HbA1c of 7.5–11.0% and an estimated glomerular filtration rate of at least 45 mL/min per 1.73 m2.
The patients were divided into those with established atherosclerotic vascular disease (63%), those with a history of heart failure (HF; 14%), and those aged 55 years and older with at least two other CV risk factors (23%), and were then randomly assigned on a 2:1 basis to receive bexagliflozin 20 mg once daily or placebo.
John McMurray, from the University of Glasgow in the UK, told delegates that after 24 weeks of treatment, HbA1c fell from a mean 8.3% at baseline to 7.4% with bexagliflozin and to 7.9% with placebo, resulting in a “highly statistically significant” difference in the mean reduction from baseline, of 0.48%. This was despite the fact that significantly fewer patients in the bexagliflozin group had rescue glucose-lowering therapy (7.1 vs 19.6%), McMurray pointed out.
Furthermore, the difference between the two groups was apparent from week 6 and persisted up to 3 years, with similar results observed among the subgroup of patients who were receiving insulin at baseline (n=834).
Among the secondary endpoints assessed, bexaglifloxin was associated with significantly greater weight loss at week 48 among participants with a baseline BMI above 25 kg/m2 (n=1378), at 3.0 versus 0.4 kg with placebo, and a significantly greater reduction in systolic blood pressure among those with a baseline level of at least 140 mmHg (n=663), at 9.8 versus 6.9 mmHg.
For time to first hospitalization with HF, bexagliflozin was noninferior to placebo, with a hazard ratio (HR) of 0.63, and despite the small number of events (23 vs 17), McMurray commented that “the effect size is as large as [that] seen in the other SGLT inhibitor trials and you see exactly the same pattern for the composite of cardiovascular death or heart failure hospitalization.”
The study drug was well-tolerated and had a similar adverse event (AE) profile to that of other SGLT2 inhibitors. Serious AEs occurred in 33.0% of people in the bexagliflozin group and 36.7% of those in the placebo group, with treatment discontinuations due to AEs reported in 8.4% and 8.5%, respectively.
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