BRENZAVVY (BEXAGLIFLOZIN) FOR TYPE-2 DIABETES

BY SAMANTHA BODAN, Pharm.D., PGY1 resident

Benzavvy™ (bexaglifozin), a new medication to help improve glycemic control in adults with type-2 diabetes (T2DM), has recently gained FDA approval. Manufactured by TheracosBio, LLC, in Massachusetts, Brenzavvy is a sodium-glucose cotransporter 2 (SGLT2) inhibitor available in 20-milligram tablets for a once-a-day dose.(1) Below are summaries of clinical trials recently published highlighting the efficacy of Brenzavvy.

In phase 3, a 24-week trial investigated the efficacy of add-on therapy in patients with T2DM. Patients were randomized to receive bexagliflozin (20 milligrams) or sitagliptin (100 milligrams) concurrently with metformin. Bexagliflozin achieved non-inferiority for the primary outcome, reduction in hemoglobin A1c (HbA1C) at 24 weeks.(2) It also demonstrated a mean change in HbA1c of - 0.74 (95 percent CI -0.86 percent to - 0.62 percent) compared to - 0.82 (95 percent CI - 0.93 percent to - 0.71 percent).(2) Secondary endpoints included changes in fasting plasma glucose (FBG), body mass and systolic blood pressure (SBP) from baseline to the 24-week period. Bexagliflozin did show significant differences compared to sitagliptin in FBG, - 1.82 millimoles per liter (mmol/L) vs. - 1.45 mmol/L (one-sided P equals 0.0123) and body mass - 3.35 kilograms vs. - 0.81 kilograms (P less than 0.0001), respectively.2 An additional secondary endpoint included the evaluation of SBP, where a mean difference of - 2.33 millimeters of mercury (mmHg) (P equals 0.0276) was observed between the bexagliflozin and the sitagliptin arm.(2)

A phase 3 multi-national trial evaluated the safety and efficacy of bexagliflozin in patients with T2DM and chronic kidney disease (CKD) compared to a placebo.(3) The primary outcome was a percent change in HbA1c from baseline to 24 weeks. Secondary outcomes included changes in body weight, SBP, albuminuria and HbA1c stratified by CKD stage. Bexagliflozin reduced HbA1c levels by an average of 0.37 percent (95 percent CI, 0.02 to 0.54 percent, P less than 0.001) compared to placebo.3 Additionally, patients with CKD stage 3a and 3b experienced average placebo corrected reductions in HbA1c of 0.31 percent (P equals 0.007) and 0.43 percent (P equals 0.002), respectively. Bexagliflozin decreased body weight by an average of 1.61 kilograms (95 percent CI, 1.00 to 2.22, P less than 0.001), SBP 3.8 mmHg (95 percent CI, 0.67 to7.1, P equals 0.02), and FPG 0.76 mmol/L (95 percent CI 0.26 to 1.26).3 Investigators also observed a placebo-adjusted reduction in albuminuria (-20.1 percent, P equals 0.03).3

The Bexagliflozin Efficacy and Safety Trial (BEST) was presented at the American Diabetes Association's eighth scientific session. The investigators evaluated the efficacy and safety of bexagliflozin (20 milligrams) compared to a placebo for glucose control, weight and blood pressure in patients with T2DM. They established cardiovascular disease or multiple risk factors for cardiovascular disease. Patients had an HbA1c of 7.5 to 11 percent and an eGFR greater than or equal to 45. Patients (n equals 1,700) were stratified into one of the following groups: established atherosclerotic CVD; heart failure; or greater than or equal to 55 years with at least two cardiovascular risk factors. The primary endpoint showed a placebo-corrected reduction in HbA1c of 48 percent (95 percent CI -0.56 to -0.39, P less than 0.0001), SBP reduced by 3.0 mmHg (95 percent -5.5 to -0.4, P equals 0.02), and decreased weight by 2.7 kilograms (-3.1 to -2.2, P less than 0.0001). These preliminary results demonstrate the greatest potential clinical impact of bexagliflozin.

SGLT2 inhibitors have revolutionized the management of T2DM, which have shown additional benefits, including weight loss, blood pressure reduction and slowing kidney disease progression.(2-5) The data from landmark trials demonstrate the beneficial effects of SGLT2 inhibitors extending to non-diabetic patients with CKD and heart failure.5 Bexagliflozin has been shown to be safe and effective in patients with diabetes and CKD stage 3b and preliminary findings of the BEST trial suggest similar effects of bexagliflozin to other licensed drugs in its class.(1-5) Experts feel this approval presents physicians with additional therapeutic options in managing patients with T2DM and has the potential to extend to non-diabetic patients with established CKD and/or heart failure.(5)

Bexagliflozin is not recommended for patients with type-1 diabetes, for treating diabetic ketoacidosis or in type-2 patients with end-stage renal disease requiring dialysis. In the aforementioned studies, bexagliflozin showed good safety and tolerability profiles.(1-5) Overall, adverse event rates were generally balanced between the intervention arm compared to the active or placebo treatment arms.(1-5) Most common adverse reactions included polyuria and mycotic infections.(5) These effects mirror similar agents on the market currently.

References available upon request