Bexagliflozin exhibits favourable glycaemic, weight, BP control in T2D patients

The highly selective SGLT2 inhibitor bexagliflozin demonstrated significant efficacy and safety in controlling hyperglycaemia, weight, and blood pressure (BP) in patients with type 2 diabetes (T2D) who were at high risk of cardiovascular (CV) events, results of the BEST* trial have shown.

“BEST met its primary and secondary efficacy endpoints,” said Dr John McMurray from the University of Glasgow in Scotland, who presented the findings at the ADA 2020 virtual meeting.

At the prespecified analysis at week 24, mean HbA_1c reduction was significantly greater with bexagliflozin vs placebo (least squares mean [LSM] change, –0.85 percent vs –0.37 percent; p<0.0001). This was observed within 6 weeks and was sustained up to the 3-year follow up mark. [ADA 2020, abstract 32-OR]

Bexagliflozin demonstrated effective glycaemic control despite the higher number of placebo recipients receiving rescue glucose-lowering therapy** (19.6 percent vs 7.1 percent), noted McMurray.

Sustained efficacy

Bexagliflozin also bested placebo in terms of HbA_1c reduction at week 24 in participants on insulin (LSM change, –0.84 percent vs –0.32 percent) and weight loss at week 48 among those with baseline BMI of ≥25 kg/m² (LSM change, –3.03 vs –0.38 kg; p<0.0001 for both). The weight loss with bexagliflozin was also apparent within 6 weeks, which continued to drop significantly over time.

There was also a rapid reduction in systolic BP at week 24 among participants with baseline systolic BP ≥140 mm Hg (LSM change, –9.83 vs –6.87 mm Hg; p=0.012). As with other endpoints, this was observed as early as 6 weeks and persisted throughout the follow up period, generating a significant overall treatment effect (p<0.0001).

Exploratory, safety endpoints

The risk of first heart failure (HF) hospitalization (hazard ratio [HR], 0.63) and the composite of CV death or HF hospitalization (HR, 0.73) were also lower with bexagliflozin vs placebo. “Despite the smaller number of events … the effect size is as large as those seen in other SGLT2 inhibitor trials,” said McMurray.

The proportion of adverse events (AEs) leading to treatment withdrawal was 8 percent in each arm. In terms of specific AEs of interest, genital mycotic infections were significantly higher with bexagliflozin vs placebo (9.5 percent 3 percent; p<0.0001). However, the fraction of patients who discontinued bexagliflozin due to such infections was only 1.2 percent.

Another notable finding was the very low percentage of participants with serious hypoglycaemia in both bexagliflozin and placebo arms (0.9 percent vs 1.4 percent) despite the high overall incidence of hypoglycaemia (42 percent vs 44 percent).

In terms of CV safety, bexagliflozin-treated patients were less likely to experience MACE*** (HR, 0.79) and MACE+^# events (HR, 0.77; p_{noninferiority}<0.0001 for both) vs placebo recipients.

A total of 1,700 high-risk patients (70 percent male, mean age 64 years, mean BMI 32.6 kg/m², mean HbA_1c 8.32 percent) were randomized 2:1 to receive bexagliflozin 20 mg QD or placebo. Of these, 63 percent had a history of atherosclerotic vascular disease, 14 percent had a history of HF, while the remaining 23 percent had ≥2 CV risk factors. Moreover, ~20 percent had kidney disease (eGFR <60 mL/min/1/73 m²). Median follow up was 123 weeks.

“[Taken together,] in high-risk T2D patients, bexagliflozin effectively reduced HbA_1c, was well-tolerated with an AE profile similar to other SGLT2 inhibitors, was associated with a low rate of treatment discontinuation, and had a good overall safety profile,” concluded McMurray.