CHICAGO – Canagliflozin outperformed sitagliptin for the treatment of patients with type 2 diabetes in the first randomized head-to-head comparison of drugs representing the two different classes of oral antidiabetic medications.
Canagliflozin (Invokana) received approval from the Food and Drug Administration in March as the first in a new class of medications for type 2 diabetes known as sodium glucose co-transporter 2 (SGLT2) inhibitors. SGLT2 is responsible for most glucose reabsorption in the kidney, so its inhibition boosts urinary glucose excretion. Other SGLT2 inhibitors are coming through the developmental pipeline.
In a phase III, double-blind, 52-week clinical trial, canagliflozin improved glycemic control, lowered body weight, and reduced blood pressure to a significantly greater extent than did sitagliptin (Januvia), a dipeptidyl peptidase-4 (DPP-4) inhibitor, Dr. Fernando Lavalle Gonzalez reported at the annual scientific sessions of the American Diabetes Association.
The multicenter four-armed study included 1,020 type 2 patients with diabetes who had inadequate glycemic control on metformin monotherapy. They were randomized to canagliflozin at 100 or 300 mg/day, sitagliptin at 100 mg/day, or 26 weeks of placebo followed by 26 weeks on sitagliptin at 100 mg/day. All participants continued on metformin.
Reductions in fasting plasma glucose at 52 weeks averaged 26.2 mg/dL in the lower-dose canagliflozin group and 35.2 mg/dL in the higher-dose group, both significantly greater than the 17.7-mg/dL decrease in patients on sitagliptin.
In addition to the better outcomes seen with canagliflozin in terms of the major efficacy endpoints involving glycemic control, weight loss, and blood pressure, the SGLT2 inhibitor resulted in a bigger boost in HDL cholesterol (see chart). On the downside, both canagliflozin and sitagliptin resulted in modest increases in low-density lipoprotein (LDL), noted Dr. Gonzalez, an endocrinologist at the Autonomous University of Nuevo Leon in Monterrey, Mexico.
Canagliflozin was associated with significantly higher rates of genital mycotic infections in both men and women, as well as more adverse events related to osmotic diuresis. The infections were symptomatic, easily diagnosed, and readily treated with topical or oral antifungals. The adverse events related to increased urination were typically mild. These side effects led to very few study discontinuations, according to Dr. Gonzalez.
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Dr. Fernando L. Gonzalez
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He said mechanistic studies have identified two factors as being responsible for the clinically meaningful reductions in blood pressure seen with canagliflozin in this study, which amounted to a mean 3.5 mm Hg decrease in systolic blood pressure at 100 mg/day and a 4.7 mm Hg reduction at 300 mg/day. It appears that about half of the blood pressure reduction is due to the negative salt and water balance, on the order of 750-1,000 cc, occurring in the first 3-4 days of treatment, and the other half is related to the weight loss accompanying canagliflozin therapy.
We all learned in medical school that gluocose is reabsorbed in the proximal renal tubule.
This particular drug inhibits this reabsorption of glucose, creating glucosuria and the consequent osmotic diuresis to a certain degree.
Because of sugar in urine, it invites urinary tract infection in women in particular and men who are not circumcised.
Amazingly it outperformed sitagliptin(Januvia) which is currently the most popular brand name drug for type 2 diabetes.