Systematic Reviews
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Dec 15, 2022; 13(12): 1168-1183
Published online Dec 15, 2022. doi: 10.4239/wjd.v13.i12.1168
Comparison of gliclazide vs linagliptin on hypoglycemia and cardiovascular events in type 2 diabetes mellitus: A systematic review
Viswanathan Mohan, Subhash Wangnoo, Sambit Das, Rajnish Dhediya, Kumar Gaurav
Viswanathan Mohan, Department of Diabetes, Madras Diabetes Research Foundation & Dr Mohan’s Diabetes Specialties Centre, Chennai 600086, Tamil Nadu, India
Subhash Wangnoo, Department of Diabetes, Apollo Hospital Education and Research Foundation, New Delhi 110001, India
Sambit Das, Department of Endocrinology, Endeavour Clinics, Bhubaneswar 750017, India
Rajnish Dhediya, Kumar Gaurav, Medical Affairs, Dr. Reddy’s Laboratories Ltd, Hyderabad 500016, India
Author contributions: Mohan V, Wangnoo S, Das S, Dhediya R and Gaurav K read and approved the final manuscript; all authors contributed equally.
Conflict-of-interest statement: There are no conflicts of interest to report.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: Rajnish Dhediya, MBBS, MD, Medical Affairs, Dr. Reddy’s Laboratories Ltd, 7-1-27 Ameerpet, Hyderabad 500016, India. rajnishd@drreddys.com
Received: July 20, 2022
Peer-review started: July 20, 2022
First decision: September 4, 2022
Revised: September 20, 2022
Accepted: October 27, 2022
Article in press: October 27, 2022
Published online: December 15, 2022
Processing time: 148 Days and 4.9 Hours
Abstract
BACKGROUND

Cardiovascular outcome trials have demonstrated cardiovascular safety of glimepiride (a sulfonylureas) against dipeptidyl peptidase-4 inhibitor linagliptin. Gliclazide (another newer sulfonylureas) has shown similar glycemic efficacy and 50% decreased risk of hypoglycemia compared to glimepiride.

AIM

Considering the absence of cardiovascular outcome trials for gliclazide, we decided to conduct a systematic review of the literature to assess the car-diovascular (CV) safety by assessing the risk for major adverse CV events and hypoglycemia risk of gliclazide vs linagliptin in patients with type 2 diabetes (T2D).

METHODS

This systematic review followed the current Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to analyze all the clinical studies published from 2008 that compared the two drugs in patients with T2D with no risk of CV disease (CVD). We included only evidence designated high quality by the Oxford Center for Evidence-based Medicine-Levels of Evidence.

RESULTS

Eight clinical studies were included in the narrative descriptive analysis (gliclazide: 5 and linagliptin: 3). The CV safety of gliclazide in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation trial and of linagliptin in the Cardiovascular and Renal Microvascular Outcome Study With Linagliptin (CARMELINA) and CARdiovascular Outcome study of LINAgliptin vs glimepiride in patients with T2D (CAROLINA) trials were excluded from the comparative analysis as these trials demonstrated CV and hypoglycemia benefits in patients at high risk of CVD. However, since these are landmark trials, they were discussed in brief to show the CV benefits and low hypoglycemia risk of gliclazide and linagliptin. We did not find any study comparing gliclazide with linagliptin. Hence, direct comparison of their major adverse CV events and hypoglycemia risk could not be carried out. However, the literature meeting the inclusion criteria showed that both drugs were effective in achieving the desired glycemic control and had low major adverse CV events and hypoglycemia risk in adult patients with no history of CVD.

CONCLUSION

Gliclazide can be considered an effective and safe glucose-lowering drug in T2D patients with no established CVD but at high risk of CVD due to their T2D status. Future randomized controlled trials comparing gliclazide with linagliptin or dipeptidyl peptidase-4 inhibitors can confirm these findings.

Keywords: Linagliptin; Gliclazide; Hypoglycemia; Major cardiovascular adverse events; Type 2 diabetes

Core Tip: This systematic review showed the lack of high-quality evidence and head-to head trials comparing the cardiovascular safety and hypoglycemia risk of gliclazide (a sulfonylurea) vs linagliptin (dipeptidyl peptidase-4 inhibitor) in adults with type 2 diabetes and no cardiovascular disease. While dipeptidyl peptidase-4 inhibitors have been proven to be cardiovascular neutral, sulfonylureas like gliclazide are commonly prescribed and recommended glucose-lowering drugs in low resource settings. Hence, it is important to establish the cardiovascular safety and hypoglycemia risk of gliclazide vs linagliptin to highlight that gliclazide may be a cost-effective yet safe treatment option for patients with type 2 diabetes.