A 12‐week, randomized, double‐blind, placebo‐controlled, four‐arm dose‐finding phase 2 study evaluating bexagliflozin as monotherapy for adults with type 2 diabetes

Abstract

Aim To compare the safety and efficacy of bexagliflozin administered as monotherapy at three dosage strengths over a 12‐week period to patients with type 2 diabetes who were either naïve to pharmacotherapy or were previously prescribed one oral hypoglycaemic agent and underwent a 6‐week period of medication abstinence. Methods Adults with type 2 diabetes (n = 292) having an HbA1c of between 7.0% and 8.5% were randomized to receive one of three dosage strengths of bexagliflozin (5, 10 or 20 mg) or placebo. The primary endpoint was the change from baseline to week 12 in the %HbA1c. Secondary endpoints included the changes from baseline in fasting plasma glucose (FPG), systolic blood pressure and diastolic blood pressure, body mass and fraction of patients achieving an HbA1c of <7%. Results The mixed model repeated measure estimates of the placebo‐adjusted change in %HbA1c from baseline to week 12 for the 5, 10 and 20 mg groups were −0.55% (95% CI: −0.76%, −0.34%, P < 0.0001), −0.68% (95% CI: −0.89%, −0.47%, P < 0.0001) and −0.80% (95% CI: −1.01%, −0.59%, P < 0.0001), respectively. Significant and dose‐dependent placebo‐adjusted mean reductions from baseline to week 12 in FPG and body mass were observed. The fraction of subjects achieving an HbA1c of <7% was significantly greater in the 20 mg bexagliflozin group. The incidence of adverse events was similar for participants in all active arms (42.3%) compared with the rate measured in those receiving placebo (40.3%). Conclusions Bexagliflozin confers substantial and dose‐dependent benefits on subjects with type 2 diabetes and has an acceptable safety profile. Further evaluation of bexagliflozin for the control of type 2 diabetes in adults is warranted.

A 96‐week, double‐blind, randomized controlled trial comparing bexagliflozin to glimepiride as an adjunct to metformin for the treatment of type 2 diabetes in adults

“…Additional benefits included a decrease in FPG and the rate of decline of eGFR, both of which were highly significant. The results of this study are consistent with previous investigations of bexagliflozin in diabetic adults, and in particular the treatment effect size agrees well with earlier estimates of −8.74 mmol/mol [−0.80%] 24‐26 …”

“…15,[18][19][20][21] Bexagliflozin is a benzylbenzene C-glycoside that is a potent selective inhibitor of human SGLT2 with an in vitro IC 50 (half-maximal inhibitory concentration) of 2.3 nM and a 2435-fold selectivity for SGLT2 compared to SGLT1. 22,23 In previous studies, bexagliflozin has been shown to produce a durable improvement in percent glycated haemoglobin (HbA1c) 24 with a placebo-adjusted effect size of 8.74 mmol/mol [0.80%] HbA1c at 12 weeks in a dose-range-finding study 25 and of 8.63 mmol/mol [0.79%] at 24 weeks, extending to 11.80 mmol/mol [1.08%] at 96 weeks in a longer-term placebo-controlled study. 24 Bexagliflozin tablets 20 mg were noninferior to sitagliptin tablets 100 mg 26 and produced a statistically significant and clinically meaningful reduction in percent HbA1c in a population of diabetic adults with Stage 3 chronic kidney disease.…”

Efficacy and safety of bexagliflozin in patients with type 2 diabetes mellitus: A systematic review and meta‐analysis

“…After removal of duplicate records and ineligible studies, 12 studies remained for full review according to prespecified criteria. Of these, six RCTs were included in this systematic review and meta‐analysis, comprising 3111 patients 14‐19 . A total of 1951 patients (62.7%) received bexagliflozin, while 1160 (37.3%) received placebo.…”

“…Of these, six RCTs were included in this systematic review and meta-analysis, comprising 3111 patients. [14][15][16][17][18][19] A total of 1951 patients (62.7%) received bexagliflozin, while 1160 (37.3%) received placebo. The follow-up period ranged from 12 to 168 weeks.…”

Basic and Clinical Pharmaco-Therapeutics of SGLT2 Inhibitors: A Contemporary Update

“…Various available SGLT2 inhibitors, and their basic pharmacological characteristics, are summarized in Table 7 [66,67,[71][72][73][74][75][76][77][78][79][80][81][82].…”