BRENZAVVY Safety and Effectiveness Compared to Dapagliflozin as an Adjunct to Metformin for Treatment of Type 2 Diabetes Mellitus in Adults
Study Design
A phase 3, randomized, double-blind, active-controlled trial compared the safety and effectiveness of BRENZAVVY, 20 mg, to dapagliflozin, 10 mg, as an adjunct to metformin for the treatment of type 2 diabetes mellitus in adults. The study population consisted of 406 participants who received BRENZAVVY or dapagliflozin in addition to ongoing metformin treatment for 24 weeks. The primary endpoint was the change in HbA1c from baseline to week 24. This clinical trial was the first to directly compare any two SGLT2 inhibitors using a randomized, double-blind, controlled design evaluating effectiveness and safety.
Study Population
The average age in the study population was 56.0 years. Enrolled patients had an average duration of diabetes of approximately 6.45 years, a mean baseline HbA1c level of 8.53%, fasting plasma glucose (FPG) of 9.59 mmol L-1, body mass of 70.2 kg, systolic blood pressure of 128 mmHg, and 2-hour postprandial blood glucose (PPG) concentration of 14.72 mmol L-1. Study patients were predominantly Asian (99.3%) and all resided in China.
HbA1c
BRENZAVVY treatment was noninferior to dapagliflozin for the management of type 2 diabetes mellitus in a population poorly controlled by metformin alone. The least-squares mean change in HbA1c from baseline to week 24 was -1.08% in the BRENZAVVY arm and -1.10% in the dapagliflozin arm. The improvement in glycemic control was considered clinically meaningful.
At week 24, 61 patients in the BRENZAVVY arm (32.3%) and 59 patients in the dapagliflozin arm (31.6%) had achieved HbA1c < 7.0%, while 23 patients in the BRENZAVVY arm (12.2%) and 21 patients in the dapagliflozin arm (11.2%) had achieved HbA1c < 6.5%.
Body Mass
BRENZAVVY or dapagliflozin treatment decreased body mass in patients from baseline to week 24. The change from baseline body mass in the BRENZAVVY arm was -2.52 kg compared to -2.22 kg in the dapagliflozin arm.
Systolic Blood Pressure
BRENZAVVY or dapagliflozin treatment decreased systolic blood pressure from baseline to week 24. The change from baseline SBP in the BRENZAVVY arm was -6.4 mmHg whereas patients in the dapagliflozin arm saw a change of -6.3 mmHg.
Fasting Plasma Glucose
BRENZAVVY or dapagliflozin treatment decreased fasting plasma glucose levels in patients from baseline to week 24. The change from baseline FPG in the BRENZAVVY arm was -1.95 mmol L-1 compared to -1.87 mmol L-1 in the dapagliflozin arm.
2-h Postprandial Plasma Glucose
BRENZAVVY or dapagliflozin treatment decreased 2-hour postprandial plasma glucose from baseline to week 24. The change from baseline PPG in the BRENZAVVY arm was -3.19 mmol L-1 whereas patients in the dapagliflozin arm saw a change of -3.05 mmol L-1 .
Safety
The number of patients that experienced adverse events was comparable between the BRENZAVVY and dapagliflozin arms. 62.6% of patients treated with BRENZAVVY and 65.0% of patients treated with dapagliflozin reported events during the trial with 4.4% and 3.5% of patients reporting serious adverse events in the BRENZAVVY and dapagliflozin arms, respectively.
REFERENCES: 1. Xie L, Han J, Cheng Z, Liu D, Liu, J, Xu C, Sun W, Li Q, Bian F, Zhang W, Chen, J, Zhu Q, Thurber TK, Lock JP. Efficacy and safety of Bexagliflozin compared with Dapagliflozin as an adjunct to metformin in Chinese patients with type 2 diabetes mellitus: a 24 week, randomized, double blind, active-controlled, phase 3 trial. Journal of Diabetes. 2024; 16(4):e13526. doi:10.1111/1753-0407.13526.