Janagliflozin

To evaluate the efficacy and safety of janagliflozin, a selective renal sodium‐glucose cotransporter‐2 inhibitor, as monotherapy in drug‐naive Chinese patients with type 2 diabetes mellitus (T2DM).

This Phase 3 trial included a 24‐week, multicentre, randomized, double‐blind, placebo‐controlled period, followed by a 28‐week extension period. A total of 432 patients with glycated haemoglobin (HbA1c) levels ≥7.0% (53 mmol/mol) and ≤10.5% (91 mmol/mol) were randomized (1:1:1) to receive once‐daily placebo, 25 mg or 50 mg janagliflozin. After 24 weeks, patients on placebo were switched and re‐randomized (1:1) to 25 mg or 50 mg janagliflozin, whereas patients on janagliflozin maintained the initial therapy. The primary endpoint was change from baseline in HbA1c after 24 weeks.

At Week 24, the placebo‐adjusted least squares mean changes in HbA1c were −0.80% (95% confidence interval [CI] −0.98% to −0.62%)/−8.7 mmol/mol (95% CI −10.7 mmol/mol to −6.8 mmol/mol) and −0.88% (95% CI −1.06% to −0.70%)/−9.6 mmol/mol (95% CI −11.6 mmol/mol to −7.7 mmol/mol), respectively (P < 0.001 for both). A higher proportion of patients achieved HbA1c <7.0% (53 mmol/mol) with janagliflozin 25 mg and janagliflozin 50 mg compared with placebo (47.2%, 49.3%, and 23.5%, respectively). Both janagliflozin doses significantly decreased fasting plasma glucose, 2‐hour postprandial glucose, body weight and systolic blood pressure, as well as increased high‐density lipoprotein (HDL) cholesterol and insulin sensitivity compared with placebo (P < 0.05 for all). The trends in improvement of these variables were sustained during the 28‐week extension period. Overall incidences of adverse events were 67.8%, 71.5% and 60.7% with janagliflozin 25 mg, janagliflozin 50 mg and placebo, respectively. The incidence of urinary tract infections and genital fungal infections was low. No severe hypoglycaemia or ketoacidosis occurred.

Janagliflozin 25 mg and 50 mg monotherapy once‐daily effectively improved glycaemic control, reduced body weight and blood pressure, improved HDL cholesterol and insulin sensitivity, and was generally well tolerated.

To evaluate the efficacy and safety of janagliflozin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin monotherapy.

This multicentre phase 3 trial included a 24‐week, randomized, double‐blind, placebo‐controlled period, followed by a 28‐week extension period. Patients (N = 421) with HbA1c of 7.0% or higher and 10.5% or less were randomized (1:1:1) to receive once‐daily placebo, janagliflozin 25 or 50 mg. After the 24‐week treatment period, patients on placebo were re‐randomized (1:1) to janagliflozin 25 or 50 mg for the additional 28‐week treatment, whereas patients on janagliflozin maintained the same therapy. The primary endpoint was the change from baseline in HbA1c to week 24.

At week 24, the placebo‐adjusted least squares mean changes of HbA1c were –0.58% and –0.58% with janagliflozin 25 and 50 mg, respectively (P < .0001 for both). The proportion of patients achieving HbA1c less than 7.0% was higher with janagliflozin 25 and 50 mg compared with placebo (41.8%, 41.7% and 28.0%, respectively). Both janagliflozin doses provided significant reductions in fasting plasma glucose, 2‐hour postprandial glucose, body weight and systolic blood pressure, and improvements in high‐density lipoprotein cholesterol and insulin sensitivity compared with placebo (P < .05 for all). The trends in improvement of these variables were retained during the 28‐week extension period. No severe hypoglycaemia occurred throughout the whole 52‐week treatment.

Janagliflozin 25 or 50 mg once‐daily added to metformin therapy significantly improved glycaemic control, reduced body weight and systolic blood pressure, improved high‐density lipoprotein cholesterol and insulin sensitivity, and was generally well‐tolerated by Chinese T2D patients who had poor glycaemic control with metformin monotherapy.