The Effect of Liraglutide Added to U-500 Insulin in Patients with Type 2 Diabetes and High Insulin Requirements

Abstract

Patients with insulin-treated type 2 diabetes and high insulin requirements are subject to undesirable treatment-related weight gain. These patients would potentially benefit from the insulin-sparing and weight loss benefits of glucagon-like peptide 1 (GLP-1) receptor agonist therapy; however, GLP-1 receptor agonists currently are not approved for use in combination with insulin. We examined the effects of adding liraglutide at a daily dose of 1.2 or 1.8 mg to an intensive regimen (either multiple daily injections or continuous subcutaneous insulin infusion) of U-500 insulin on hemoglobin A1c (HbA1c), total daily insulin dose, and weight in 15 patients with type 2 diabetes and high insulin requirements (initial mean daily insulin dose of 192 ± 77 units per day; initial mean weight, 300.9 ± 55.7 lbs) in a clinical practice setting. In this observational case series, we identified 15 patients treated with a combination of U-500 insulin and liraglutide for at least 12 weeks at routine follow-up office visits. The U-500 insulin dose was reduced by 0-30% upon initiation of liraglutide. Insulin doses were subsequently adjusted to optimize glycemic control. Endpoints included change in HbA1c, change in total daily insulin dose, change in weight, and incidence of hypoglycemia. Comparisons of 12-week and baseline values were evaluated by paired two-tailed t tests. At 12 weeks, the reduction in HbA1c from baseline (8.48%) was 1.4% (P = 0.0001). Weight fell by an average of 11.2 LB (5.1 KG) (P = 0.0001). Total daily insulin dose was reduced by 28% (P = 0.0001). No severe episodes of hypoglycemia occurred. Adding liraglutide to U-500 insulin resulted in significant improvements in glycemic control, weight loss, and reduced insulin requirements in patients with type 2 diabetes and high insulin requirements.