Canagliflozin plus insulin improves glycaemic control, reduces body weight in T2DM patients
Combination therapy with canagliflozin and insulin is effective in improving glycaemic control and reducing body weight and well tolerated by Japanese patients with type 2 diabetes mellitus (T2DM), according to a study presented at the 53rd European Association for the Study of Diseases (EASD 2017) held in Lisbon, Portugal.
“This regimen provides a novel option in the treatment of patients with T2DM who require additional treatment,” researchers said.
In this double-blind, placebo-controlled study, patients with inadequate glycaemic control despite insulin, diet and exercise therapies were randomly assigned to either placebo (n=70) or canagliflozin 100 mg (n=76) that were administered once daily in addition to their prior insulin therapy. The change in glycated haemoglobin (HbA1c) levels from baseline to week 16 was the primary endpoint.
HbA1c levels from the baseline significantly decreased in the canagliflozin group (−0.97±0.08 percent) compared with the placebo group (0.13±0.08 percent) at week 16. The decrease in HbA1c levels in patients given canagliflozin was independent of the insulin treatment (premixed, long-acting and long-acting plus rapid- or short-acting). [Cardiovasc Diabetol 2016;15:89]
“The decrease in HbA1c levels here was slightly greater than that observed in a previous study in non-Japanese patients, including Caucasians (difference between placebo and canagliflozin at 18 weeks, −0.62 percent), suggesting that the effects of canagliflozin are independent of the pathologic features among races. A significant decrease in HbA1c levels was observed regardless of the type of the insulin regimen,” researchers said. [Diabetes Care 2015;38:403–11; Curr Med Res Opin 2015;31:1693–702]
Canagliflozin, compared with placebo, also significantly reduced fasting plasma glucose levels (−34.1±4.8 vs −1.4±5.0 mg/dL) and body weight (−2.13±0.25 vs 0.24±0.26 percent), and significantly increased high-density lipoprotein (HDL) cholesterol (3.3±1.0 vs −0.5±1.0 mg/dL) and homeostasis model assessment 2 steady-state beta-cell function (HOMA2- %B; 10.15±1.37 vs 0.88±1.42 percent).
“The results of the present study demonstrated that the combination of canagliflozin and insulin, regardless of the insulin regimen, controlled plasma glucose levels without causing weight gain in Japanese patients with T2DM who were inadequately controlled by insulin,” researchers said.
“Interestingly, canagliflozin combination with insulin slightly increased HOMA2- %B, suggesting improved beta-cell function. This is possibly resulting from a reduction of glucotoxicity,” they added. [Diabetes Care 2015;38:2344–53; Cardiovasc Diabetol 2015;17:142]
Both the placebo and canagliflozin groups showed similar overall incidence of adverse events. The incidence and incidence per patient-year exposure of hypoglycaemia (hypoglycaemic symptoms and/or decreased blood glucose) were slightly higher in the canagliflozin group (40.0 percent and 7.97) than in the placebo group (29.6 percent and 4.51).
Hypoglycaemic events in both groups, however, were mild in severity and dose-reduction of insulin by <10 percent from baseline following hypoglycaemic events lowered the incidence per patient-year exposure in the canagliflozin group. There was no between-group difference in the incidence of hypoglycaemia according to the insulin regimen.
“[T]he incidence per [patient]-year exposure decreased in patients undergoing insulin dose reduction following a hypoglycaemic event. These findings suggest that adjusting the insulin dose of the combined regimen prevents the occurrence of hypoglycaemic events,” researchers said.
One of the limitations of this study is the short course of treatment, which is why it has been extended for up to 52 weeks. Also, patients treated with insulin in the form of an intermediate-acting or rapid-acting product were not included, and there were a small number of patients in each type of insulin subgroup. Thus, the investigators did not deliberate which insulin regimen fit better with canagliflozin.