A new study published June 27 in The Lancet showed that linagliptin, a dipeptidyl peptidase-4 inhibitor, is non-inferior to glimepiride, a frequently used sulphonylurea, in patients with type 2 diabetes.
While "metformin is widely accepted as the first-line oral agent in the treatment of type 2 diabetes," metformin alone is often insufficient in maintaining glycaemic control due to a loss of insulin secretory function. According to the authors, "when metformin alone is insufficient, the choice of second-line treatment is challenging, and there is no clear consensus on the optimum approach."
Combining a sulphonylurea and metformin to improve glycemic control is currently the most common approach; however, hypoglycemia and weight gain are potential consequences.
The study looked at type 2 diabetic outpatients with glycated hemoglobin A1c (HbA1c) 6∙5-10∙0 percent on solely metformin or on metformin as well as an oral antidiabetic drug who were randomly assigned to daily oral doses of either linagliptin (5 mg) or glimepiride (1-4 mg). Out of the 777 patients who were randomly assigned to linagliptin and 755 to glimepiride, results showed there were fewer patients with hypoglycemia or severe hypoglycemia with linagliptin versus glimepiride. The study also found that patients treated with linagliptin alone or in combination with metformin resulted in reductions of HbA1c and a low risk of hypoglycemia and no weight gain—showing that linagliptin is associated with fewer cardiovascular events overall.
According to the authors, "the results of this long-term randomized active-controlled trial advance the clinical evidence and comparative effectiveness bases for treatment options available to patients with type 2 diabetes mellitus. The findings could improve decision making for clinical treatment when metformin alone is insufficient."
In a related editorial comment, Andre J. Scheen, MD, and Nicolas Parquot, MD, of the University of Liege in Belgium note that, "high-quality comparative research is needed, not only on HbA1c reduction during the first year after treatment, but also over a longer period to study the durability of effectiveness."
"Only long-term trials with incretin-based treatments would provide enough data for both efficacy and safety to draw firm conclusions about the real value of this new approach," add the authors.