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This study investigated the effects of co-administering losartan with metformin or glibenclamide on γ‐glutamyl transferase (GGT) activity in a rat model of hypertension and diabetes induced by L‐NAME and streptozotocin (STZ). Male Wistar rats were divided into normotensive/non-diabetic controls, hypertensive/diabetic controls, and hypertensive/diabetic groups treated with either losartan/metformin or losartan/glibenclamide. GGT activity was measured in both plasma and liver tissues to assess systemic and hepatic responses. While plasma GGT levels remained unchanged across all groups, liver GGT activity was significantly elevated in hypertensive/diabetic rats compared to controls, indicating increased hepatic oxidative stress and potential liver dysfunction. Treatment with either drug combination showed a trend towards reducing liver GGT activity; however, these changes did not reach statistical significance. The findings suggest that the liver is more susceptible to the combined effects of hypertension and diabetes, and that the current dosing regimen of losartan/metformin or losartan/glibenclamide may be insufficient to modulate this hepatic marker. Further research is needed to optimize treatment strategies and to explore additional markers of liver function in this context.
