Kidney Week

Abstract: FR-OR144

Safety and Effectiveness of Bexagliflozin in Type 2 Diabetes Mellitus and Stage 3a/3b CKD: A Phase 3 Randomized Clinical Trial

Session Information

• High-Impact Clinical Trials
  October 26, 2018 | Location: 20A, San Diego Convention Center
  Abstract Time: 11:00 AM - 11:15 AM

Category: Diabetic Kidney Disease

• No subcategory defined

Authors

• Allegretti, Andrew S., Massachusetts General Hospital , Boston, Massachusetts, United States

Andrew S. Allegretti, MD, MS

• Thurber, Tara K., Massachusetts General Hospital , Boston, Massachusetts, United States

Tara K. Thurber,

• Zhang, Wenbin, Shanghai JiaYue PharmaTech Ltd, Shanghai, China

Wenbin Zhang,

• Zhou, Wenjiong, FMD K&L, Langhorne, Pennsylvania, United States

Wenjiong Zhou,

• Freeman, Mason W., Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States

Mason W. Freeman,

• Halvorsen, Yuan-Di C., Massachusetts General Hospital , Boston, Massachusetts, United States

Yuan-Di C. Halvorsen,

Background

Hyperglycemia exacerbates the progression of chronic kidney disease (CKD), but most glucose-lowering therapies seldom address morbidities associated with CKD. Sodium-glucose cotransporter-2 (SGLT2) inhibitors offer potential benefits to diabetics with CKD but their utility may be diminished with impaired renal function.

Methods

A phase 3, double-blind, placebo-controlled, multi-center, multi-national, randomized trial was conducted to evaluate the safety and effectiveness of bexagliflozin, a novel SGLT2 inhibitor, in patients with type 2 diabetes and stage 3a/3b CKD. Patients were randomly assigned to receive bexagliflozin or placebo for 24 weeks. The placebo-adjusted change in hemoglobin A_1c was the primary endpoint. Secondary endpoints were changes in body weight, systolic blood pressure, albuminuria, fasting plasma glucose and hemoglobin A_1c stratified by CKD 3a/3b status. Efficacy data were analyzed using repeated measures methodology with intent to treat population to demonstrate treatment effects at 24 weeks.

Results

312 patients across 54 sites were analyzed. Bexagliflozin lowered hemoglobin A_1c by 0.37% (95% CI 0.20, 0.54, p <0.0001) compared to placebo. Patients with CKD stage 3a (eGFR 45 to <60) and 3b (eGFR 30 to <45) had reductions in hemoglobin A_1c of 0.31% (p = 0.0068) and 0.43% (p = 0.0017), respectively. Bexagliflozin lowered body weight (1.61 kg, p <0.0001), systolic blood pressure (3.8 mmHg, p = 0.02), fasting plasma glucose (0.76 mmol/L, p =0.0029) and albuminuria (geometric mean ratio reduction of 20.1%, p = 0.027). Adverse events were comparable between groups.

Conclusion

Bexagliflozin was effective for lowering hemoglobin A_1c in diabetic patients with stage 3a/3b CKD and was well tolerated. Additional benefits in this population were reduction in body weight, systolic blood pressure, fasting plasma glucose and albuminuria.

Funding

• Commercial Support – Theracos LLC