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World J Diabetes. Apr 15, 2023; 14(4): 424-434
Published online Apr 15, 2023. doi: 10.4239/wjd.v14.i4.424
Semaglutide-eye-catching results
Maja Cigrovski Berkovic, Felice Strollo
Maja Cigrovski Berkovic, Faculty of Kinesiology, University of Zagreb, Zagreb 10000, Croatia
Felice Strollo, Department of Endocrinology and Metabolism, IRCCS San Raffaele Pisana, Rome 00163, Italy
Author contributions: Cigrovski Berkovic M conceived and wrote the original draft; Strollo F was involved in data collection and analysis and writing the manuscript; both authors approved the final version of the manuscript.
Conflict-of-interest statement: The authors declare no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Maja Cigrovski Berkovic, MD, PhD, Adjunct Associate Professor, Faculty of Kinesiology, University of Zagreb, 15 Horvacanski zavoj, Zagreb 10000, Croatia. maja.cigrovskiberkovic@gmail.com
Received: December 15, 2022
Peer-review started: December 15, 2022
First decision: January 20, 2023
Revised: February 8, 2023
Accepted: March 20, 2023
Article in press: March 20, 2023
Published online: April 15, 2023
Processing time: 117 Days and 19.1 Hours
Abstract

Semaglutide is a glucagon-like peptide-1 receptor agonist used either orally every day or subcutaneously once a week for the treatment of type 2 diabetes mellitus and, more recently, at higher doses, for the treatment of obesity. Both diseases are reaching epidemic proportions and often coexist, posing patients with a high risk for cardiovascular disease and death. Therefore, an agent such as semaglutide, which offers clinically significant weight loss and cardiovascular benefits, is essential and will be increasingly used in high-risk patients. However, during the SUSTAIN clinical trial program (Semaglutide Unabated Sustainability in treat-ment of type 2 diabetes), a safety issue concerning the progression and worsening of diabetic retinopathy emerged. The existing explanation so far mainly supports the role of the magnitude and speed of HbA1c reduction, a phenomenon also associated with insulin treatment and bariatric surgery. Whether and to which extent the effect is direct is still a matter of debate and an intriguing topic to investigate for suitable preventative and rehabilitative purposes. In this minireview, we will summarize the available data and suggest guidelines for a comprehensive semaglutide clinical utilization until new evidence becomes available.

Keywords: Glucagon-like peptide-1 receptor agonists; Semaglutide; Diabetic retinopathy; Microvascular complications; Cardiovascular benefit; Rehabilitation

Core Tip: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) benefit patients with type 2 diabetes mellitus in terms of glucose management, weight control, oxidative damage, and prevention of adverse renal and cardiovascular events without increasing the of risk of hypoglycemia. After reviewing the literature to investigate upon such a clinically relevant issue, the authors found that: Semaglutide per se seems to cause no direct damage to the retina, and the reported adverse effects might even be ascribed to a bias in the trial design. Special attention to the retinopathy status should be paid at present when using semaglutide in older patients with longstanding diabetes.