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The study indicates that Annona squamosa when given along with Glipizide in combination not only controls the blood glucose level but also reduces the dosage of Glipizide by 25 to 50 percent. Our results also showing that, with these reduced dosage of Glipizide, Annona squamosa also controls the total cholesterol, triglycerides and elevates HDL-C levels. On the basis of strong out comes of study we can say that this combination also provides the renoprotection and improves psychopharmacological performance. It was also concluded from the data that A. squamosa leaf extract supplementation along with reduced and reducing doses of Glipizide improves the lipid metabolism and prevents diabetic complications from lipid peroxidation and antioxidant systems in experimental type-2 diabetic rats. This combination could be useful for prevention of not only diabetes but also their complications. However, longer duration studies of A. squamosa and its isolated compounds with Glipizide on chronic models are necessary to establish long term safety in animals and humans and to develop a potent combination of antidiabetic drug.