If blood sugar levels are controlled, this risk is reduced, but many people with type 2 diabetes are unable to achieve blood sugar goals, partly due to the low efficacy and adverse side-effects of available drugs. New findings reported by Richard Pratley, M.D., of the University of Vermont College of Medicine, compared the effectiveness of injections of a recently FDA-approved drug called liraglutide to sitagliptin, a commonly-used oral treatment, in controlling blood glucose levels in type 2 diabetes patients who have inadequate control on the standard treatment metformin. The study results appear in an “Article Online First” and in the April 24 issue of the journal Lancet.
“The most significant finding is that liraglutide was substantially better than sitagliptin,” said Pratley, professor of medicine and director of the Diabetes and Metabolism Translational Medicine Unit at UVM and Fletcher Allen Health Care. “The second major finding is that liraglutide leads to weight loss in the majority of patients. On average, participants lost more than six pounds, whereas most other medications cause weight gain, which is a significant problem in our patients with type 2 diabetes who are often already overweight.”
According to Pratley, roughly 10 to 12 million people with type 2 diabetes in the U.S. are treated with the oral drug metformin, which helps increase the body’s response to insulin, a hormone that helps regulate blood sugar levels. Both liraglutide and the oral drug sitagliptin, which was FDA-approved in 2006, increase secretion of insulin, aiding decreased blood sugar levels, and decreased secretion of the hormone glucagon, which prevents blood sugar levels from increasing again. However, the two drugs have a different mechanism of action: Lirgaglutide requires injection, while sitagliptin can be taken orally. Liraglutide promotes weight loss and causes nausea in some patients, while sitagliptin does not cause weight loss and rarely causes nausea. Data is rare for direct comparisons of these two drug types. Thus, the authors compared the two directly in patients who had inadequate blood sugar control on metformin alone.
In this randomized trial, patients aged 18 to 80 years with type 2 diabetes mellitus who had inadequate blood glucose control and taking metformin daily for at least three months were enrolled and treated at office-based sites in Europe, the U.S., and Canada. Participants received 26 weeks’ treatment with 1.2 mg. or 1.8 mg. injections of liraglutide once daily or 100 mg. sitagliptin orally once daily. The primary endpoint was change in hemoglobin A1c or HbA1c* — the standard blood glucose measurement used in type 2 diabetes monitoring — from baseline to week 26.
The researchers found greater lowering of mean HbA1c (8.5 percent at baseline) was achieved with a 1.8 mg. dose of liraglutide (-1.50 percent) and 1.2 mg. dose of liraglutide (-1.24 percent) than with sitagliptin (-0.90 percent). Estimated mean treatment differences for liraglutide versus sitagliptin were –0.60 percent for 1.8 mg. and –0.34 percent for 1.2 mg. liraglutide. Nausea was more common with liraglutide (59 [27 percent] patients on 1.8 mg.; 46 [21 percent] on 1.2 mg.) than with sitagliptin (10 [5 percent]). Minor hypoglycaemia (very low blood sugar levels) was recorded in about 5 percent of participants in each treatment group. But overall, both drugs were well tolerated.
“A 0.6 percent difference is large,” said Pratley. “For example, in the registration trials for sitagliptin, a 0.6 percent difference was typically seen against placebo.”
Pratley and his co-authors point out that in the UK Prospective Diabetes Study Group trial, a one percent reduction in HbA1c was associated with a 37 percent decreased risk of microvascular complications and a 21 percent decreased risk of death related to diabetes, making their study findings regarding the differences in HbA1c between liraglutide and sitagliptin clinically relevant. The group concludes that these findings support the use of liraglutide as an effective agent to add to metformin.
*Note: HbA1c is used to indicate the average plasma glucose concentration of the preceding two to three months. In general, the reference range (that found in healthy persons who do not have diabetes), is about 4 percent to 5.9 percent. Patients with diabetes usually have HbA1c levels above 6.5 percent.
(This news release was adapted from a release produced by The Lancet titled “Injected Liraglutide is Better than Oral Sitagliptin for Blood Glucose Control in Type 2 Diabetes”.)