Treatment Strategy for Type 2 Diabetes with Obesity: Focus on Glucagon-like Peptide-1 Receptor Agonists

Purpose: The progressive nature of type 2 diabetes mellitus (T2DM) calls for step-wise intensification of therapy for maintaining normal glycemic levels and lowering cardiovascular (CV) risk. Because obesity is a prominent risk factor and comorbidity of T2DM, it further elevates the CV risk in T2DM. Therefore, it is vital to manage weight, obesity, and glycemic parameters for effective T2DM management. Few oral antidiabetic drugs (sulfonylureas and thiazolidinediones) and insulin are not suitable for obese patients with T2DM because these drugs cause weight gain. The present review discusses the place of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the treatment of obese patients with T2DM and the significance of these drugs in the prevention of future CV risk in patients with T2DM. Methods: A literature search of PubMed and EMBASE was conducted by using the search terms T2DM, GLP-IRAs, obesity, and cardiovascular complication. Randomized controlled trials measuring the effect of GLP-1RAs versus that of placebo on CV outcomes were included in the review. Findings: GLP-1RAs have emerged as a therapeutic alternative; these drugs exert their actions by providing glycemic control, improving insulin resistance and 6-cell function, and reducing weight. The risk of hypoglycemia with GLP-1RAs is minimal; however, GLP-1RAs are associated with gastrointestinal adverse events and raise concerns regarding pancreatitis. Combining GLP-1RAs with insulin analogues results in higher efficacy, a lowered insulin dose, and reduced insulin-related hypoglycemia and weight gain. Longer acting GLP-1RAs are also associated with improvement in medication adherence. Improvement in CV risk factors such as blood pressure and lipid profile further increases their usability for improving CV outcomes. Implications: Overall, the properties of GLP-1RAs make them suitable for combination with oral anti diabetic drugs in the early stages of T2DM and with insulins in the later stages for optimizing comprehensive management of the disease. (Clin Ther. 2017;39:1244-1264) (C) 2017 Elsevier HS Journals, Inc. All rights reserved.