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Mini-Reviews in Medicinal Chemistry


ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Review Article

Role of GLP-1 Analogs in the Management of Diabetes and its Secondary Complication

Author(s): Ponnurengam Malliappan Sivakumar, B. Premkumar *, Veluchamy Prabhawathi and Pranav Kumar Prabhakar*

Volume 21, Issue 20, 2021

Published on: 22 April, 2021

Page: [3166 - 3182] Pages: 17

DOI: 10.2174/1389557521666210422114909

Price: $65


Abstract: The cardiovascular complications of Type 2 Diabetes Mellitus (T2DM) including myocardial infarction, heart failure, peripheral vascular disease and, stroke and retinopathy, nephropathy and neuropathy are microvascular complications. While the newer therapies like glitazones or even Dipeptidyl- peptidase-IV (DPP-IV) inhibitors increase the risk of therapy, the Glucagon Like Peptide-1 Receptor Agonists (GLP-1RAs), were reported as suitable alternates. The GLP-1RAs reduce Major Adverse Cardiovascular Events (MACE), have anti-atherogenic potential, and possess pleiotropic activity. The GLP-1RAs were found to improve neuroprotection, enhance neuronal growth, reduce the incidence of stroke, and improve central insulin resistance. The GLP-1RAs are beneficial in improving the glycemic profile, preventing macroalbuminuria and reducing the decline in eGFR and enhancing renal protection. The renal benefits of add-on therapy of GLP-1RAs with SGLT-2 inhibitors have composite renal outcomes such as suppression of inflammatory pathways, improvement in natriuresis, diuresis, found to be nephroprotective. Improvement in glycemic control with a reduction in body weight and intraglomerular pressure and prevention of tubular injury makes the GLP-1RAs as suitable add-on therapies in improving cardiorenal outcomes. Obesity, an important contributor to insulin resistance and a reduction in weight, is an essential therapeutic option in addressing diabetic-obesity. It also reduces the damage to blood-retinal-barrier, thus beneficial in halting the development of diabetic retinopathy. In diabetic complications, glycemic control, addressing insulin resistance through weight loss, controlling atherosclerosis through anti-inflammatory effects and cardio-renal-neuro protection, makes GLP-1RAs a suitable therapeutic strategy on long-term treatment of T2DM. This review discusses the role of GLP-1RAs in diabetes, the dosage, mono or combination therapy with other antidiabetics in long-term treatment and its effect in uncontrolled diabetes.

Keywords: Glucagon like peptide-1, dipeptidyl-peptidase, diabetes, neuropathy, retinopathy, microvascular complications.

Graphical Abstract

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