Is the new drug Canagliflozin (Invokana) effective in type 2 diabetes?

The authors reviewed the use of canagliflozin (Invokana) in type 2 diabetes.

For type 2 diabetes, initial treatment with metformin (Glucophage) as a single therapy when lifestyle intervention is inadequate followed by additional agents such as insulin or sulfonylureas is typically recommended. However, many of these drugs increase the risk of hypoglycaemia (dangerously low blood sugar levels) or may lead to weight gain which may worsen insulin resistance. Thus, new anti-diabetes drugs that provide long-term glycemic control with minimal hypoglycaemia and weight gain are needed.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of diabetes medication. These drugs promote glucose excretion through the kidneys in order to lower blood sugar levels. Canagliflozin is the first drug of this class to be approved in the US for type 2 diabetes. This article provided a review of the effectiveness and safety of canagliflozin.

10 randomized clinical trials were included in this review. Trial duration ranged from 12 to 52 weeks. Patients were mainly middle-aged and overweight adults who had type 2 diabetes for more than 4 years. All trials evaluated canagliflozin 300 mg administered orally once daily. HbA1c level (a measurement of average blood glucose levels over the past 3 months) was used to evaluate the effectiveness of canagliflozin.

Compared to placebo (substance with no therapeutic effect), canagliflozin resulted in a 1.08% greater decrease in HbA1c level when evaluated as a single therapy, and a 0.73% greater decrease in HbA1c level when evaluated in combination with other therapies.  Patients treated with canagliflozin were 2.41 times more likely to achieve HbA1c levels of less than 7% compared to those taking placebo.

Compared with an active comparator (another diabetes drug such as sitagliptin or glimepiride), canagliflozin resulted in a 0.21% greater decrease in HA1c level. Canagliflozin reduced HbA1c level 0.24% more than sitagliptin (Januvia) and 0.12% more than glimepiride (Amaryl).

Compared with both placebo and an active comparator, canagliflozin resulted in a greater decrease in fasting plasma glucose levels (glucose levels after 8 hours without food). Compared with placebo, canagliflozin resulted in a 2.81kg greater decrease in body weight, and a 3.49 kg greater decrease in body weight compared to active comparator. Canagliflozin reduced body weight 2.84 kg more than sitagliptin and 5.4 kg more than glimepiride. Canagliflozin resulted in greater decreases in systolic (pressure when the heart is contracting) and diastolic blood pressure (pressure when the heart is relaxing) compared to both placebo and an active comparator. 

No severe hypoglycemic events were reported in most studies. The risk of hypoglycaemia with canagliflozin 300 mg was deemed to be 13% higher than placebo, but this was not statistically significant. However, the incidence of hypoglycaemia was 49% higher with canagliflozin than placebo in patients who were also taking a sulfonylurea or insulin.

The authors concluded that treatment with canagliflozin provided significant reductions in HbA1c levels in patients with type 2 diabetes, while also showing the potential to reduce weight gain.

Many of the studies were of 26 weeks' duration, and longer studies are warranted to confirm these findings.