Janssen has announced that the investigational agent Canagliflozin substantially lowers blood glucose levels compared to placebo when used as add-on therapy in patients with type 2 diabetes who are inadequately controlled with the antihyperglycemic agents Metformin and Pioglitazone. These results were presented at the 4th World Congress on Controversies to Consensus in Diabetes, Obesity, and Hypertension ( CODHy ).

The data presented are the latest Phase 3 results for Canagliflozin, which is being evaluated across a spectrum of patients with type 2 diabetes. Results from the study ( known as DIA3012 ) has showed that Canagliflozin, dosed once daily at 100 mg or 300 mg in addition to Metformin and Pioglitazone, had statistically greater A1C reductions at 26 weeks relative to placebo ( change from baseline, -0.89% and -1.03%, vs. -0.26%, respectively, p less than 0.001 ). The overall incidence of adverse events was generally similar across all treatment arms.

In secondary efficacy endpoint measures of the study, both the Canagliflozin 100 mg and 300 mg dose groups provided reductions in body weight compared to placebo ( -2.8% and -3.8% vs -0.1%, respectively, p less than 0.001 ) and reductions in systolic blood pressure ( -5.3 mmHg, p less than 0.01 and -4.7 mmHg, p less than 0.05, vs -1.2 mmHg, respectively ).
Reductions in fasting plasma glucose were consistent with the primary endpoint for Canagliflozin 100 mg and 300 mg, compared to placebo ( -1.49 and -1.84 mmol/L vs 0.14 mmol/L, respectively, p less than 0.001 ).
Increases in high-density lipoprotein cholesterol were observed with Canagliflozin 100 mg and 300 mg, compared to placebo [ 7.2% ( 0.08 mmol/L ), p less than 0.05, and 8.9% ( 0.10 mmol/L ), p less than 0.001, vs 2.4% ( 0.02 mmol/L ), respectively ], and increases in low-density lipoprotein cholesterol were also seen [ 7.1% ( 0.08 mmol/L ) and 11.3% ( 0.19 mmol/L ) vs -0.4% ( -0.10 mmol/L ), respectively ].
Canagliflozin has decreased triglyceride levels at the 300 mg dose [ -1.7% ( -0.16 mmol/L ), p less than 0.01 ) ]. Triglyceride levels increased at the 100 mg dose [ 3.1% ( -0.06 mmol/L ), p=ns ) ], though placebo was associated with a higher increase [ 15.3% ( 0.10 mmol/L ) ].

The incidence of adverse events leading to discontinuation was low and similar across treatment groups ( 3.5% for Canagliflozin total and 5.2% for placebo ). Most adverse events were assessed by the investigator as mild to moderate in intensity, and the overall incidence of adverse effects was balanced across treatment arms.
Adverse events of genital mycotic infections in men and women, and increased frequency of urination ( pollakiuria ) were more common with Canagliflozin 100 mg and 300 mg compared to placebo in men and women; these specific adverse events were generally mild or moderate in intensity and did not lead to discontinuation. Rates of urinary tract infections and hypoglycemia were low and similar across groups.

Canagliflozin is an investigational sodium glucose co-transporter 2 ( SGLT2 ) inhibitor for the treatment of patients with type 2 diabetes. The kidneys of people with type 2 diabetes reabsorb greater amounts of glucose back into the body compared to non-diabetic people, which may contribute to elevated glucose levels. Canagliflozin blocks the reabsorption of glucose by the kidney, increasing glucose excretion and lowering blood glucose levels.

Source: Janssen Research & Development, 2012

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