Incretin-based therapy offers alternative option for treating type 2 diabetes

A review of previous studies indicates that use of a class of medications known as "incretin-based therapy", which act via certain pathways that affect glucose metabolism may provide modest effectiveness and favorable weight change outcomes for the treatment of type 2 diabetes and may represent an alternative to other hypoglycemic therapies, according to an article in the July 11 issue of JAMA: The Journal of the American Medical Association.

Current therapies for type 2 diabetes are often limited by adverse effects such as weight gain or hypoglycemia (low blood sugar). A more recent class of treatment to address these issues is incretin therapy, which involves glucose-stimulated insulin secretion by intestinally derived peptides, which are released in the presence of glucose or nutrients in the gut, according to background information in the article. In October 2006 the Food and Drug Administration approved the first oral incretin enhancer, sitagliptin, a selective DPP4 inhibitor (a class of oral hypoglycemics), for use as monotherapy or in combination with other medications. The effectiveness of this class of medications in managing type 2 diabetes is not well understood.

Renee E. Amori, M.D., of Tufts-New England Medical Center, Boston, and colleagues conducted a meta-analysis of 29 studies to assess the effectiveness and safety of incretin-based therapy (GLP-1 analogues and DPP4 inhibitors) in nonpregnant adults with type 2 diabetes.

“Our analysis of randomized controlled trials showed that incretin-based therapy with GLP-1 analogues or DPP4 inhibitors in adults with type 2 diabetes is moderately effective in improving glycemia, with greater reductions in postprandial [after a meal] glycemia and favorable (GLP-1 analogues) or neutral (DPP4 inhibitors) effects on weight. Glucagon [a hormone secreted by the pancreas]-like peptide 1 analogues were associated with gastrointestinal adverse effects, while DPP4 inhibitors had a slightly increased risk of infection (nasopharyngitis [inflammation of the nasal passages] and urinary tract infection) and headache,” the authors write.

“Incretin therapy offers an alternative option to currently available hypoglycemic agents for nonpregnant adults with type 2 diabetes with modest efficacy and a favorable weight change profile,” they write. “Individuals with mild diabetes, suggesting an adequate pancreatic beta cell reserve, who are at risk of hypoglycemic sequelae and in need of weight loss may benefit from this new class. However, these new classes of hypoglycemic agents will need continued evaluation both in long-term efficacy and safety controlled trials and in clinical practice to assess their effectiveness and safety profile to determine their role among the many available and well-established therapies for type 2 diabetes.”

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