Insulin plus incretin: A glucose-lowering strategy for type 2-diabetes

Abstract

There are many advantages of combining incretin therapy [glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors] with insulin therapy as a glucose-lowering strategy in type 2 diabetes. One important advantage is the complementary mode of the mechanistic action of incretin and insulin therapy. Another advantage is the reduction in risk of hypoglycemia and weight gain when adding incretin therapy to insulin. Several clinical trials have studied the addition of GLP-1 receptor agonists [exenatide BID (twice daily), lixisenatide, albiglutide] or DPP-4 inhibitors (vildagliptin, sitagliptin, saxagliptin, alogliptin, linagliptin) to ongoing insulin therapy or adding insulin to ongoing therapy with a GLP-1 receptor agonist (liraglutide). These studies show improved glycemia in the presence of limited risk for hypoglycemia and weight gain with the combination of incretin therapy with insulin. This article reviews the background and clinical studies on this combination.

Keywords: Type 2 diabetes, Glucose lowering, Insulin therapy, Glucagon-like peptide-1 receptor agonists, Dipeptidyl peptidase-4 inhibitors, Incretin therapy, Combination

Core tip: Incretin therapy (glucagon-like peptide-1 receptor agonists or dipeptidyl peptidase-4 inhibitors) combined with insulin therapy is a glucose-lowering strategy in type 2 diabetes. The combination allows a complementary mode of mechanistic action and, as demonstrated in several clinical trials, is glucose-lowering in association with limited risk for hypoglycemia and weight gain. The combination is a promising strategy in patients in whom metformin with either incretin therapy or basal insulin is insufficient for adequate glycemic control. This article reviews the background and clinical studies on this combination.