Comparative toxicological analysis of metformin (Biguanide) and glibenclamide (Sulfonylureas), using zebrafish embryotoxicity test (ZFET)

Abstract

Background and Objective: Type 2 (T2DM) and gestational diabetes mellitus (GDM) among pregnant Filipinos have been increasing over the years because of lifestyle westernization. While insulin has been the safe mainstay when dietary measures fail to maintain normoglycemia during pregnancy, recent studies have suggested oral hypoglycemic agents (OHAs) such as metformin and glibenclamide, may offer cheaper and efficacious alternatives. The problem however, is the passage of these drugs through the placenta which may pose possible danger towards the development of the growing embryo. The proposed study aims to evaluate and compare the embryotoxic and teratogenic potentials of the varying concentrations of the two PhilHealth covered oral hypoglycemic agents in the Philippines, namely metformin (biguanide) and glibenclamide (sulfonylureas).

Methodology: In this study, a comparison on embryotoxic potentials of metformin and glibenclamide was conducted using zebrafish embryotoxicity test (ZFET) across concentrations found in fetal (10, 20, 100, 500, 1000, 2000 μg/L) and maternal serum (10, 20, 100, 500, 1000, 2000 mg/L).

Results and Conclusions: Results revealed that metformin showed no significant (p>0.05) lethal effects, but revealed significant risk for teratogenicity, specifically decreased head and tail lengths and advanced hatching. Conversely, glibenclamide revealed significant potential for lethal (e.g., coagulation) and teratogenic effects including pericardial and yolk sac edema, spinal deformity and increased tail length. Comparative evaluation between the two OHAs reveal that glibenclamide has significantly (p<0.05) higher lethal and teratogenic effects. Together, our results suggest that the use of metformin over glibenclamide is favorable for safety testing in pregnant women suffering T2DM and GDM for the benefit of expanding treatment options for these diseases.