CardioExchange Archive

Sulfonylureas are often added to metformin to improve glycemic control, but at the known risk of increasing hypoglycemia and weight gain. In a report published in the Lancet, more than 1,500 patients with type 2 diabetes taking metformin were randomized to the addition of either linagliptin, a dipeptidyl peptidase-4 inhibitor, or glimepiride, a sulfonylurea.

After two years, the trial achieved the prespecified criterion for noninferiority as treatment with both drugs resulted in a similar effect on HbA1c. Both hypoglycemia and weight gain were reduced in patients taking linagliptin. There was only one case of severe hypoglycemia in the linagliptin group, compared with 12 cases in the glimepridie group. In addition, although there were only a small number of cardiovascular (CV) events, a significant reduction was observed in the linagliptin group.

• Reduction in mean HbA1c: −0.16% for linagliptin vs. −0.36% for glimepiride (difference 0.20%, CI 0.09–0.30)
• Hypoglycemia: 7% for linagliptin vs. 36% for glimepiride (p<0.0001)
• Weight: −1.4 kg vs.  +1.3 kg (p<0.0001)
• CV events: 12 vs. 26 events (RR 0.46, CI 0.23—0.91, p=0.0213)

The results, write the authors, “support the use of linagliptin in combination with metformin as a therapeutic option for treatment of type 2 diabetes.”

In an accompanying editorial, André Scheen and Nicolas Paquot discuss the potential benefits of linagliptin and other DPP-4 inhibitors. They note that the smaller reduction in HbA1c with linagliptin “might support the view of a slightly lower efficacy of DPP-4 inhibitors compared with sulphonylureas,” but  say that only a trial with longer followup can assess the durability of glucose lowering with DPP-4 inhibitors. In the meantime, the effects on weight and the lower rate of hypoglycemia are “important to patients with diabetes” and can improve quality of life.

However, firm conclusions about the drugs can not be reached until long-term trials with cardiovascular outcomes are completed. These trials will “provide enough data for both efficacy (i.e., effects on diabetic complications) and safety (i.e., concerns about pancreatitis and pancreatic cancer) to draw firm conclusions about the real value of this new approach.”