Comparative embryotoxicological analysis of metformin (Biguanide) and glibenclamide (Sulfonylureas), using Zebrafish Embryotoxicity Test (ZFET)

Abstract

Type 2 and Gestational Diabetes Mellitus among pregnant Filipinos have been observed to progress per decade as a probable result of lifestyle westernization. While insulin has been the safe mainstay when dietary measures fail to maintain normoglycemia during pregnancy, recent studies have suggested that PhilHealth-covered oral hypoglycemic agents (OHAs), metformin (MET) and glibenclamide (GLIB), may be contending cheaper and efficacious alternatives; however, confirmed passage of these drugs through the placenta pose possible danger towards the development of the growing embryo. In this study, a comparison on embryotoxic potentials of the two aforementioned OHAs was conducted using 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 show that MET groups show no significant lethal effects, but reveal significant risk for teratogenicity - specifically decreased head and tail length and advanced hatching. Conversely, GLIB groups reveal significant potential for lethal - coagulation - and teratogenic effects - delayed hatching, pericardial and yolk sac edema, spinal deformity and increased tail length. Comparative evaluation between the two OHAs reveal that GLIB has significantly higher lethal and teratogenic outcomes; hence, the use of MET over GLIB is statistically favorable for safety testing in pregnant women suffering T2DM and GDM for the benefit of expanding treatment options of these diseases in the Philippines.