The Effect of Sitagliptin, Pioglitazone and Dapagliflozine on Myocardial Infarction in Diabetic Rats
NCT ID: NCT07083232
Last Updated: 2025-08-14
Study Results
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Basic Information
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COMPLETED
PHASE4
50 participants
INTERVENTIONAL
2024-10-30
2024-11-30
Brief Summary
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Detailed Description
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Myocardial ischemia represents a condition of sufferance for cardiomyocytes due to coronary blood flow reduction as compared to their metabolic needs, and it may exhibit through several clinical conditions.
People with type 2 diabetes mellitus are at increased risk of cardiovascular disease, heart failure and death, as compared with the general population. Studies show that the excess risks associated with diabetes mellitus are mediated primarily by hyperglycemia and overall poor risk factor control. Effective treatment of traditional cardiovascular risk factors has reduced the excess risk of atherosclerotic cardiovascular disease , such as acute myocardial infarction and stroke in people with type 2 diabetes mellitus.
In the last two decades, several studies have demonstrated reductions in the risk of cardiovascular outcomes and mortality in patients with type 2 diabetes mellitus with improved glucose and cholesterol-lowering therapies. Nevertheless, macrovascular disease remains the most common cause of death in type 2 diabetes mellitus patients and new diabetes therapies are highly desired, especially if they can offer cardiovascular benefits.
Sitagliptin is a potent and highly selective dipeptidyl peptidase-4 competitive inhibitor that does not affect the closely related enzymes dipeptidyl peptidase-8 or dipeptidyl peptidase-9 at therapeutic concentrations.
Sitagliptin found to enhance circulating glucagon-like peptide-1 levels through inhibition of dipeptidyl peptidase -IV activity.
which, in turn, provides cardiovascular protection probably through the anti-inflammatory and anti-atherosclerotic activities of glucagon-like peptide-1. Reduces blood glucose levels, in either the postprandial or the fasting state.
Multiple studies have suggested that pioglitazone, a peroxisome proliferatoractivated receptor γ agonist, used as an insulin-sensitizing agent in the treatment of type 2 diabetes mellitus , may have anti-atherosclerotic effects.
The mechanism of action of dapagliflozine influences a number of cardiovascular disease risk factors, in particular, decreasing blood pressure, reducing body weight (predominantly through reductions in total body fat mass, including visceral adipose tissue), reducing waist circumference, and lowering albuminuria and serum uric acid levels, with allow intrinsic risk of hypoglycemia.
Isoprenaline is a potent β-adrenergic agonist, increases the myocardial oxygen demand by mixture of its positive inotropic and chronotropic actions. Administration of isoprenaline in high doses to animals produces infarct like lesions in the heart similar to those present in myocardial infatction in humans.
The aim of the present study is to evaluate the prophylactic effect of Sitagliptin, Pioglitazone and Dapagliflozine on Isoprenaline induced myocardial infarction in type II diabetic rats.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
NONE
Study Groups
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standard normal diet and water group
Group I: formed of normal animals. They were allowed standard normal diet and water. They received no drugs.
standard normal diet
Group I: formed of normal animals. They were allowed standard normal diet and water. They received no drugs
low dose Streptozotocin group
Group II: Non-treated diabetic rats; diabetes was induced by administration of 20% fructose solution in drinking water for 2 weeks, then intra peritoneal injection of a low dose STZ (40 mg/kg b.w.)
low dose Streptozotocin
Non-treated diabetic rats; diabetes was induced by administration of 20% fructose solution in drinking water for 2 weeks, then intra peritoneal injection of a low dose STZ (40 mg/kg b.w.), was done
Sitagliptin group
Group III: Sitagliptin treated diabetic group sitagliptin was administered by gastric gavage in a dose 10mg/ kg /day for 4 weeks
Sitagliptin (Novartis, USA)
Sitagliptin treated diabetic group sitagliptin was administered by gastric gavage in a dose 10mg/ kg /day for 4 weeks
Pioglitazone group
Group IV : Pioglitazone treated diabetic group ; Pioglitazone was administered by gastric gavage in a dose 10 mg/ kg /day for 4 weeks
Pioglitazone hydrochloride (Unipharma., Egypt)
Pioglitazone treated diabetic group (G4); Pioglitazone was administered by gastric gavage in a dose 10 mg/ kg /day for 4 weeks
Dapagliflozine group
Group V : Dapagliflozine treated diabetic group (G5); Dapagliflozine was administered by gastric gavage in a dose 1mg/ kg /day for 4 weeks
Dapagliflozine hemihydrate (Janssen, USA)
Dapagliflozine treated diabetic group (G5); Dapagliflozine was administered by gastric gavage in a dose 1mg/ kg /day for 4 weeks
Interventions
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standard normal diet
Group I: formed of normal animals. They were allowed standard normal diet and water. They received no drugs
low dose Streptozotocin
Non-treated diabetic rats; diabetes was induced by administration of 20% fructose solution in drinking water for 2 weeks, then intra peritoneal injection of a low dose STZ (40 mg/kg b.w.), was done
Sitagliptin (Novartis, USA)
Sitagliptin treated diabetic group sitagliptin was administered by gastric gavage in a dose 10mg/ kg /day for 4 weeks
Pioglitazone hydrochloride (Unipharma., Egypt)
Pioglitazone treated diabetic group (G4); Pioglitazone was administered by gastric gavage in a dose 10 mg/ kg /day for 4 weeks
Dapagliflozine hemihydrate (Janssen, USA)
Dapagliflozine treated diabetic group (G5); Dapagliflozine was administered by gastric gavage in a dose 1mg/ kg /day for 4 weeks
Eligibility Criteria
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Inclusion Criteria
Exclusion Criteria
MALE
No
Sponsors
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Al-Azhar University
OTHER
Responsible Party
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El Shazly Abdelaal Mohaseb
Assistant lecturer of pharmacology
Locations
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Alazher University.assuit Branch
Asyut, , Egypt
Countries
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Other Identifiers
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MD/AZ.AST./PHA006/8/231/5/2024
Identifier Type: -
Identifier Source: org_study_id
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