Lancet: Liraglutide better than sitagliptin for certain diabetes patients

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For type 2 diabetes patients whose glucose levels cannot be controlled with metformin, treatment from an injection of liraglutide (Victoza, Novo Nordisk), rather than sitagliptin (Januvia, Merck), provides better glucose control, according to a trial published in the April 22 issue of the Lancet.

“Although good glycemic control can decrease the risk of microvascular, and possibly macrovascular complications, many people with type 2 diabetes are not achieving glycemic goals, partly because of the low efficacy and adverse side-effects of available drugs,” wrote the authors.

Richard E. Pratley, MD, of the University of Vermont, College of Medicine in Burlington, Vt., and colleagues compared the effectiveness of liraglutide and sitagliptin to control glucose levels in 665 type 2 diabetes mellitus patients aged 18 to 80 between June 16, 2008, and June 11, 2009.

In the parallel-group, open-label clinical trial, the researchers evaluated three arms: 221 patients treated with 1.2 mg of subcutaneous liraglutide; 225 patients treated with a 1.8 mg injection of liraglutide once daily; and 219 patients administered 100 mg of oral sitagliptin once daily.

The patients were selected at random to receive the aforementioned treatments and received treatment over a period of 26 weeks. The primary endpoint measured was the change in HbA1c (average plasma glucose concentration) at 26 weeks.

After the 26-week follow-up, results showed that HbA1c declined by 1.5 percent, 1.24 percent and 0.9 percent in patients treated with 1.8 mg of liraglutide, 1.2 mg of liraglutide and sitagliptin, respectively.

For patients who exhibited a baseline HbA1c of 9 percent or higher, after treatment of 1.8 mg of liraglutide, HbA1c levels decreased by 1.9 percent. These same rates declined by 2.2 percent and 1.4 percent for patients treated with 1.2 mg of liraglutide and sitagliptin, respectively.

The researchers found that more patients treated with liraglutide achieved target levels of HbA1c as defined by the American Diabetes Association (less than 7 percent) or by the National Institute of Clinical Health and Excellence, American Association of Clinical Endocringologists and the International Diabetes Federation (6.5 percent or lower).

However, the authors reported that almost 5 percent of patients in each arm had reports of hyperglycemia.

Additionally, the results showed declines in fasting plasma glucose levels by 2.14 mmol/L, 1.87 mmol/L and 0.83 mmol/L for patients treated with 1.8 mg of liraglutide, 1.2 mg of liraglutide and sitagliptin, respectively.

According to the authors, previous trials have shown that a 1 percent decline of HbA1c is associated with a 37 percent decrease in risk of microvascular complications and a 21 percent decrease in the risk of death associated with diabetes.

The authors wrote that patients administered 1.8 mg of liraglutide showed better patients satisfaction than those administered sitagliptin, “despite the fact that liraglutide was given by injection and sitagliptin was given by injection and sitagliptin was taken orally.”

"Liraglutide was superior to sitagliptin for reduction of HbA1c, and was well tolerated with minimum risk of hypoglycemia. These findings support the use of liraglutide as an effective agent to add to metformin,” the authors concluded.

In an accompanying editorial, André J. Scheen, MD, and Régis P. Radermecker, MD, of the University of Liège in Belgium, recommended that a 1.2 mg dose of liraglutide be the starting dose for patients with type 2 diabetes but be increased to 1.8 mg if HbA1c target levels are unreachable.

“Even though Pratley and colleagues recorded superior treatment satisfaction with 1.8 mg liraglutide than with sitagliptin, the gastrointestinal tolerance profile is better with sitagliptin than with liraglutide, and one pill of sitagliptin daily might be judged as easier to administer than one subcutaneous injection of liraglutide daily,” they concluded.