The Synergistic Effect of Combined Linagliptin and Metformin Improves Hepatic Function in High-fat Diet/Streptozotocin-induced Diabetic Rats

Background: Monotherapy for liver dysfunction in diabetes is less effective. This study investigated the effect of combined linagliptin and metformin therapy on liver function in diabetic rats. Methods and materials: Sixty-four mature male (200-300 g) Wistar rats were used. Streptozotocin (35 mg/kgb.wt) was repeatedly injected intraperitoneally to induce diabetes. The rats were grouped into eight groups (n = 8). Group I: control; Group II: control + 10 mg/kgb.wt linagliptin; Group III: control + 200 mg/kgb.wt metformin; Group IV; control + 10 mg/kgb.wt linagliptin + 200 mg/kgb.wt metformin; Group V: diabetic; Group VI: diabetic + 10 mg/kgb.wt linagliptin; Group VII: diabetic + 200 mg/kgb.wt metformin; Group VIII: diabetic + 10 mg/kgb.wt linagliptin + 200 mg/kgb.wt metformin. The animals were sacrificed on the last day of the experiment, blood and liver samples were collected for biochemical assay. Results: Insulin, blood glucose, glycated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-cholesterol), liver function biomarkers, liver glucose metabolic enzymes, malondialdehyde and inflammatory markers increased (p < 0.05) significantly. High-density lipoprotein-cholesterol (HDL-cholesterol), liver antioxidant, glycogen, and glycogen synthase were reduced significantly in diabetic rats. Linagliptin and metformin administration single and combined reduced the insulin, blood glucose, glycated hemoglobin, total cholesterol, triglycerides, LDL-cholesterol, liver function biomarkers, liver glucose metabolic enzymes, malondialdehyde, and inflammatory markers, and increased the HDL-cholesterol, liver antioxidant, glycogen and glycogen synthase in diabetic rats Conclusion: Linagliptin monotherapy alone efficiently controls hyperglycemia and remarkably improves liver functions. Combining linagliptin and metformin could be used as safe and effective therapy for liver dysfunction progression in diabetes.