Abstrakt

Combination therapy with metformin and the GLP-1 analogue liraglutide as a synergistic treatment for diabetic retinopathy in a type-2 diabetic rat model

Tourki A. S. Baokbah

This study investigated the effect of combination therapy with metformin and Glucagon-Like Peptide-1 (GLP-1) analogue, liraglutide, as a synergistic treatment for Diabetic Retinopathy (DR) in Type-2 Diabetes (T2DM). Normal rats and rats with established T2DM were divided equally into five groups. Group I: Normal non-diabetic rats, Group II: T2DM rats, Group III: T2DM rats administered metformin (30 mg/ kg) once daily for 12 weeks, Group IV: T2DM rats administered liraglutide (75 μg/kg) once daily for 12 weeks, and Group V: T2DM rats administered liraglutide (75 μg/kg) and metformin (30 mg/kg) once daily for 12 weeks. In each group, retinal morphology was observed using Haematoxylin-Eosin (H&E) staining. Lipid peroxidation (malondialdehyde) and endogenous antioxidant enzyme (catalase) levels were measured using a colorimetric method. Expression of autophagy (LC3&P62) and apoptosis (caspase-3) markers and Transforming Growth Factor-β (TGF-β) was detected using immunohistochemistry. H&E staining revealed that the T2DM group had evident retinal damage, which could be effectively improved using combination therapy with metformin and liraglutide compared with the two monotherapy treatments. Combined therapy improved the antioxidant ability of injured retinal tissue in the T2DM group by significantly (P?0.01) down regulating and restoring the levels of malondialdehyde and catalase, respectively. The low expression of TGF-β, LC3, and P62; and the high expression of caspase-3 in the retinal tissues of the T2DM group was significantly (P?0.01) reversed through combined treatment. Therefore, metformin combined with liraglutide synergistically attenuated DR in a T2DM rat model by inhibiting oxidative stress, apoptosis, and TGF-β expression while activating autophagy