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14-02-2012 | Diabetes | Article

Canagliflozin improves glycemic control in insulin-refractory diabetes


Free abstract

MedWire News: Patients with diabetes who show poor glycemic control despite insulin therapy could benefit from canagliflozin, a potent and selective inhibitor of the sodium-glucose co-transporter 2 (SGLT2), results of randomized trial show.

This study was conducted to provide an initial evaluation of the safety and tolerability of the addition of canagliflozin to diabetes care and indeed found no deaths, serious adverse events, or severe hypoglycemic episodes.

Patients with Type 2 diabetes often require insulin therapy to control glucose level as their illness progresses; however, many patients still do not achieve glycemic goals.

"As SGLT2 inhibition is a glucose-lowering mechanism distinct from that of current antihyperglycemic agent (AHA) classes, it would be expected to provide efficacy in combination with other AHA classes, including insulin," Damayanthi Devineni (Janssen Research and Development, New Jersey, USA) and colleagues comment.

They therefore conducted a randomized, double-blind, placebo-controlled, parallel-group, 28-day study at two sites, in 29 Type 2 diabetes patients who were not optimally controlled on insulin and up to one oral AHA. Patients were treated with canagliflozin 100 mg once daily or 300 mg twice daily or placebo.

The researchers found that A1C, fasting plasma glucose decreased in patients administered canagliflozin from -0.19% with placebo, to -0.73% with 100 mg once daily, and -0.92% with 300 mg twice daily.

Likewise bodyweight change showed a trend for reduction with canagliflozin, with a 0.03 kg increase with placebo, 0.73 kg reduction with 100 mg once daily, and 1.19 kg reduction with 300 mg twice daily.

Although six patients in the canagliflozin group experienced at least one symptomatic treatment-emergent hypoglycemic episode, none were classified as severe or serious and no patients discontinued treatment.

Devineni et al comment: "As the insulin independent mechanism of action of canagliflozin preserves the glucose-responsiveness of β-cell insulin secretion, the intrinsic risk of hypoglycemia is limited.

"However, AHAs can increase the risk of insulin-induced hypoglycemia by improving glycemic control, thereby reducing the 'cushion' above the hypoglycemic threshold."

They add that larger and longer-term studies will be needed to fully evaluate the risk for hypoglycemia with the use of canagliflozin in combination with insulin therapy.

The findings are published in Diabetes, Obesity and Metabolism.

MedWire ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012

By Andrew Czyzewski

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