Evaluation of GLP-1 Receptor Agonists in Combination With Multiple Daily Insulin Injections for Type 2 Diabetes

Abstract

Objective: To assess the available literature evaluating the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with multiple daily insulin injections (MDII). Data Sources: A literature search of MEDLINE and Embase was performed (2004 to May 2020) using the following search terms: glucagon-like 1 receptor agonist, liraglutide, albiglutide, dulaglutide, exenatide, semaglutide, diabetes mellitus, and prandial insulin or bolus insulin. Additional references were obtained from cross-referencing the bibliographies of selected articles. Study Selection and Data Extraction: All information obtained from the searches were reviewed. All relevant trials are included in this review. Data Synthesis: Eight studies met criteria for inclusion. The addition of a GLP-1 RA to multiple daily insulin injections was associated with a reduction in A1c in 7 out of 8 studies, and weight loss in 5 studies. In studies that allowed insulin adjustment after the addition of GLP-1 RA, the average total daily insulin dose was reduced in 3 studies. When evaluated, hypoglycemia frequency or other adverse events were not increased when GLP-1 RAs were added to MDII. Relevance to Patient Care and Clinical Practice: Guidelines do not offer recommendations regarding the use of GLP-1 RAs in combination with MDII regimens. This review evaluates current studies demonstrating efficacy and safety considerations of this combination. Conclusions: While some studies did demonstrate an improvement in A1c and reduction in insulin doses without increased hypoglycemia, larger randomized controlled trials are needed to adequately assess the benefit and safety of GLP-1 RAs in combination with MDII.