Published online Dec 15, 2022. doi: 10.4239/wjd.v13.i12.1168
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
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.
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).
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.
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.
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.
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.