Transitioning to Fixed-Ratio Combination Therapy: Five Frequently Asked Questions Health Care Providers Should Anticipate From Their Patients.

Abstract

A patient who is overweight with type 2 diabetes and takes multiple oral antihyperglycemic agents has been informed that the current treatment plan is not providing adequate glycemic control and that adding insulin therapy is recommended. However, the patient is concerned about insulin causing weight gain or leading to hypoglycemia and is looking for a treatment that will avoid or reduce these issues. Taking all of these considerations into account, the health care provider recommends that the patient start insulin and a glucagon-like peptide 1 (GLP-1) receptor agonist given as fixed-ratio combination (FRC) therapy administered with a prefilled pen device that allows for both basal insulin and a GLP-1 receptor agonist to be delivered in a single daily injection. Basal insulin and GLP-1 receptor agonists have different but complementary modes of action. Basal insulin predominantly regulates blood glucose between widely spaced meals and overnight (1) through the movement of glucose from blood into certain cells of the body (including skeletal muscle) and the suppression of hepatic glucose production (2); GLP-1 receptor agonists affect glucose control through glucose-dependent insulin secretion, slowing gastric emptying, inducing satiety, and suppressing excess postprandial glucagon release (3). FRC therapies that contain both a basal insulin and a GLP-1 receptor agonist have been shown to improve glycemic control with a risk of hypoglycemia that is similar to that associated with the use of basal insulin alone (4,5). In addition, FRC therapies have been shown to mitigate insulin-induced weight gain and to reduce the likelihood of the gastrointestinal (GI) adverse events that are associated with the use of GLP-1 receptor agonists. This effect is the result of slower up-titration of the GLP-1 receptor agonist component of an FRC compared with the titration schedule recommended when a GLP-1 receptor agonist is used alone (6–8). …