Impact of Current and Emerging Glucose-Lowering Drugs on Body Weight in Type 2 Diabetes

Abstract

Type 2 diabetes is a progressive disease, and most people with diabetes will eventually require adjunctive pharmacotherapy to optimize their glycemic control. As the majority of people with type 2 diabetes are overweight or obese, weight management is an essential component of diabetes management to improve their overall health and quality of life. Many of the currently available glucose-lowering drugs are associated with weight gain, which makes it challenging for both prescribing clinicians and patients. The 2015 Canadian Diabetes Association Clinical Practice Guidelines interim update on the pharmacologic management of type 2 diabetes recommend individualization of therapy and glycemic targets. Clinicians should take into consideration not only the drug's efficacy and safety profiles but also its propensity for causing hypoglycemia and weight gain. Given that the number of glucose-lowering drugs is expanding rapidly, a better understanding of the impacts of current and emerging therapies on body weight will serve as a useful guide. Metformin remains the first-line drug after diet and exercise therapy. The next add-on agent could be selected from the incretin or sodium-glucose cotransporter-2 inhibitor class because these drugs rarely cause hypoglycemia and may lead to modest weight loss. When insulin therapy is considered, choosing a basal insulin that is associated with less nocturnal hypoglycemia and weight gain is recommended. Emerging therapies using combination therapy of an incretin-sodium-glucose cotransporter 2 inhibitor or glucagon-like peptide-1 agonist-basal insulin hold promise to achieve robust glycemic control with weight loss and low risk for hypoglycemia.

Keywords: agonistes des récepteurs du GLP–1 (glucagon-like peptide–1); dipeptidyl peptidase-4 inhibitors; glucagon-like-peptide-1 agonists; glucose-lowering drugs; hypoglycémiants; inhibiteurs de la dipeptidyl peptidase–4; inhibiteurs du cotransporteur sodium-glucose de type 2; insulin/insulin secretagogues; insuline/sécrétagogues de l'insuline; sodium-glucose cotransporter-2 inhibitors.