Saturday , November 25 2017
Home / Resources / Articles / Canagliflozin Versus Glimepiride in T2DM Patients Taking Metformin

Canagliflozin Versus Glimepiride in T2DM Patients Taking Metformin

Canagliflozin shows good results when compared to glimepiride in type 2 diabetes patients who were taking metformin…

A global team of researchers assessed the efficacy and safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT-2), when compared with glimepiride over a period of 104 weeks in patients with type 2 diabetes who were inadequately controlled with metformin.

This is a phase 3 randomized, double-blind actively controlled study. There were a total of 1,450 patients who received canagliflozin 100 or 300 mg or glimepiride (titrated up to 6 or 8 mg/day) during a 52-week core period. After the core period the study was followed by a 52-week extension period. The primary end point was the change in A1c from baseline to week 52. The secondary end points assessed at week 104 included change in A1c, fasting plasma glucose, and systolic and diastolic BP; percentage change in body weight and fasting plasma lipids (including triglycerides, HDL cholesterol [HDL-C], LDL cholesterol [LDL-C], LDL-C/HDL-C ratio, and non–HDL-C); and the proportion of patients achieving A1C <7.0%.

See more SGLT-2 Resources

At week 104, reductions from baseline A1C were -0.65%, -0.74%, and -0.55% with canagliflozin 100 and 300 mg and glimepiride. A durability analyses showed sustained A1c lowering with both canagliflozin doses when compared to glimepiride. Reductions in body weight (-4.1%, -4.2%, and +0.9%, respectively) and systolic blood pressure (-2.0, -3.1, and +1.7 mmHg, respectively) were observed with canagliflozin 100 and 300 mg compared with glimepiride at week 104. The overall incidence of adverse events over the entire 104-week treatment period was higher with canagliflozin 300 mg and glimepiride (77.9% and 78.4%, respectively) than with canagliflozin 100 mg (73.3%). The incidences of adverse effects leading to discontinuation were 6.2%, 9.5%, and 7.3%, respectively, with canagliflozin 100 and 300 mg and glimepiride. Incidences of genital mycotic infections, urinary tract infections, and osmotic diuresis related adverse events were higher with canagliflozin than glimepiride; these were reported to be generally mild to moderate in intensity and led to very few discontinuations. Fewer patients had hypoglycemic events with canagliflozin 100 and 300 mg than glimepiride (6.8%, 8.2%, and 40.9%). Mild decreases in estimated glomerular filtration rate occurred initially in patients who were taking canagliflozin; this occurrence decreased over 104 weeks.

In conclusion, canagliflozin was shown to provide durable glycemic improvements, body weight and blood pressure reductions when compared with glimepiride. In most cases canagliflozin was safe and well tolerated in patients with type 2 diabetes who were also receiving treatment with metformin over the period of 104 weeks. Discontinuation from adverse events was the lowest in the canagliflozin 100 mg group.

Practice Pearls:

  • There was a greater decrease in body weight in the canagliflozin groups when compared to glimepiride in T2DM patients receiving metformin.
  • Beneficial reductions in blood pressure were greater in the canagliflozin groups when compared to glimepiride in T2DM patients receiving metformin.
  • Risk for hypoglycemia in the canagliflozin groups were very low compared to glimepiride in T2DM patients receiving metformin.

Lawrence A. Leiter. “Canagliflozin Provides Durable Glycemic Improvements and Body Weight Reduction Over 104 Weeks Versus Glimepiride in Patients With Type 2 Diabetes on Metformin: A Randomized, Double-Blind, Phase 3 Study”. Diabetes Care. March 2015;38:355–364