BRENZAVVY Safety and Effectiveness in Patients as an Adjunct to Metformin
Study Design
A phase 3, randomized, double-blind, placebo-controlled trial evaluated the effectiveness and safety of BRENZAVVY, 20 mg, in adults with type 2 diabetes mellitus as an adjunct to metformin. 317 adults received BRENZAVVY, 20 mg, or placebo in addition to ongoing metformin treatment for 24 weeks. Eligible patients were stratified based on baseline HbA1c (> 8.5% or not) and country of residence. The primary endpoint was the change in HbA1c from baseline to week 24.
An open label group enrolled an additional 34 patients with HbA1c > 10.5 and ≤ 12.0% and was analyzed separately.
Study Population
The average age in the double-blind group was 55.8 years. Enrolled patients had an average duration of diabetes of approximately 9.1 years, a mean baseline HbA1c level of 8.6%, fasting plasma glucose (FPG) of 189 mg dL-1 and systolic blood pressure (SBP) of 129 mmHg. 52.1% of patients had a baseline HbA1c < 8.5% at baseline while 47.9% had baseline HbA1c between 8.5 and 10.5%. 47.6% of study patients were from Japan while 52.4% of patients resided in the United States.
The majority of the open label group resided in the United States (79.4%) and the average age was 52.1 years. The average duration of diabetes was approximately 9.2 years and the mean baseline values for HbA1c, FPG, and SBP were 11.1%, 239.6 mg dL1 and 131 mmHg, respectively.
HbA1c
BRENZAVVY treatment improved glycemic control in patients. The reduction of 1.09% from baseline HbA1c and the placebo-corrected treatment effect of −0.53% was clinically meaningful and statistically significant. Rescue medication was provided to 38 patients (6 in the BRENZAVVY arm and 32 in the placebo arm). Exclusion of values observed after treatment with rescue medication gave a reduction of 1.07% from baseline HbA1c and a placebo-corrected treatment effect of −0.67%.
The open label group had a mean change in HbA1c of −2.82% after 24 weeks of BRENZAVVY treatment.
Fasting Plasma Glucose
BRENZAVVY treatment decreased fasting plasma glucose levels in patients. The change from baseline FPG in the BRENZAVVY arm was −45.2 mg dL-1 with a placebo-adjusted change of −24.3 mg dL-1.
Systolic Blood Pressure
BRENZAVVY treatment decreased systolic blood pressure. The change from baseline SBP in the BRENZAVVY arm was −5.03 mmHg with a placebo-adjusted reduction of −7.07 mmHg as patients in the placebo arm had an overall increase from baseline of 1.67 mmHg.
The open label group had a mean change in SBP of −8.19 mmHg after 24 weeks of BRENZAVVY treatment.
REFERENCES: 1. Halvorsen YD, Conery AL, Lock JP, Zhou W, Freeman MW. Bexagliflozin as an adjunct to metformin for the treatment of type 2 diabetes in adults: A 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2023; 1- 9. doi: 10.1111/dom.15192. PMID: 37409573.