Evaluating the Long-term Efficacy and Safety of SGLT2 Inhibitor Canagliflozin in Older Patients with Type 2 Diabetes

During a session at the American Diabetes Association’s 74th Scientific Sessions, held June 13-17, 2014, in San Francisco, CA, Bruce Bode, MD, Clinical Associate Professor in the Department of Medicine at Emory University in Atlanta, GA, spoke on the use of the SGLT2 inhibitor canagliflozin in the treatment of older patients with type 2 diabetes.

In describing the challenges of treating this group of patients, Bode said, “Managing type 2 diabetes in older patients requires consideration of the impact of advancing age and comorbidities on the benefit/risk profiles of the anti-hyperglycemic agents used when treating this group. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, has demonstrated improvement in glycemic control, bodyweight, and blood pressure across a broad population of patients with type 2 diabetes, including older individuals.”

The long-term efficacy and safety of canagliflozin were evaluated over a 104-week period in a randomized, double-blind, placebo-controlled study in patients 55-80 years of age with type 2 diabetes inadequately controlled on a stable anti-hyperglycemic agent regimen. Patients were randomized to canagliflozin 100 mg, canagliflozin 300 mg, or placebo. A total of 714 patients entered the trial with mean age of 63.6 years, mean HbA1C level of 7.7%, mean fasting plasma glucose of 156.8 mg/dL, and mean BMI of 31.6 kg/m².

Efficacy endpoints at week 104 were changes from baseline in HbA1c, fasting plasma glucose, bodyweight, systolic blood pressure, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Statistical testing of canagliflozin compared with placebo was not conducted (not pre-specified) for analyses of efficacy parameters at week 104; therefore no P values were reported. Over 104 weeks, canagliflozin 100 mg and 300 mg reduced HbA1C, fasting plasma glucose, bodyweight, and systolic blood pressure. Small increases in HDL-C and LDL-C were observed in the 2 canagliflozin groups compared with those receiving placebo.

Regarding overall safety and tolerability, Bode reviewed selected adverse events observed through week 104, saying, “Canagliflozin was associated with increased incidence of genital mycotic infections and adverse events related to osmotic diuresis compared with placebo but was overall generally well tolerated over 104 weeks. The incidence of documented hypoglycemia was higher with both canagliflozin doses than with placebo. There were few severe episodes of hypoglycemia in any of the groups.”

Bode summarized the results of the study, saying, “In older patients with type 2 diabetes inadequately controlled by their current regimens, canagliflozin at the 100 mg and 300 mg doses improved glycemic control, reduced bodyweight, and lowered blood pressure compared with placebo over 104 weeks. Increases in HDL-C and LDL-C were observed with canagliflozin compared with placebo at week 104. LDL-C levels plateaued after 26 weeks.”

“Canagliflozin was efficacious in treating older patients with type 2 diabetes and was generally well tolerated over 104 weeks. The efficacy and safety profile of canagliflozin in this study is consistent with that seen in other phase 3 studies of canagliflozin across a broad range of patients with type 2 diabetes,” Bode said.