What question did this study set out to answer?

This study aims to evaluate the effects of tirzepatide on metabolic and systemic complications in a diabetic rat model.

May 6, 2026Open Access

Tirzepatide Ameliorates Renal Dysfunction, Dyslipidemia, and Thyroid Hormone Dysregulation in Diabetic Rats

Key Points

This study aims to evaluate the effects of tirzepatide on metabolic and systemic complications in a diabetic rat model.
Experimental diabetes was induced in rats with a single injection of streptozotocin (50 mg/kg).
Rats were divided into control, diabetic, tirzepatide alone, and diabetic plus tirzepatide groups.
Biochemical markers such as glucose, BUN, creatinine, and lipid profiles were monitored throughout the study.
Survival rates were higher in control, tirzepatide alone, and diabetic plus tirzepatide groups compared to a 10% mortality in the diabetic group.
Tirzepatide partially attenuated increases in BUN and creatinine, indicating renal protective effects.
Tirzepatide significantly decreased triglycerides and increased HDL-C, while showing no impact on cholesterol or LDL-C.

Abstract

Background: Tirzepatide (TZP), a dual glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide 1 (GLP-1) receptor agonist, has shown potential in improving glycemic control. However, its effects on diabetes mellitus (DM)-related systemic complications remain less defined. This study investigated the impact of TZP on metabolic, cardiovascular, renal, and thyroid parameters in a rat model of DM. Methods: Experimental DM was induced in rats via a single intraperitoneal injection of streptozotocin (50 mg/kg). Animals were allocated into four groups: control (saline), DM, TZP alone (1.35 mg/kg, cyclic dosing), and DM+TZP (streptozotocin followed by five TZP injections). Survival, body-weight, and serum biochemical markers were monitored, including glucose, insulin, troponin I, Creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), creatinine, cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), thyroid-stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3). Results: Survival was preserved in the control, TZP alone, and DM+TZP groups, whereas mortality reached 10% in the DM group. Body weight decreased significantly in the DM and DM+TZP groups, with a modest reduction in the TZP alone group. TZP markedly increased hyperglycemia and LDH levels without altering troponin I or CK-MB levels. DM-associated elevations in BUN and creatinine were partially attenuated by TZP, suggesting renoprotective effects. TZP had no impact on cholesterol or LDL-C, but significantly decreased triglycerides and increased HDL-C. Additionally, TZP modulated thyroid hormone levels, as reflected by increased T4 and decreased T3 concentrations compared with diabetic rats. Conclusions: In this experimental DM model, TZP improved glycemic control, ameliorated renal dysfunction, and favorably modulated lipid metabolism and thyroid axis activity, with no evidence of overt myocardial necrosis observed based on troponin I and CK-MB; additional studies incorporating histology and/or functional assessments are needed to evaluate subclinical cardiac effects. These findings indicate the therapeutic potential of TZP in mitigating DM-associated complications beyond glucose regulation.

Bookmark

View Full Paper

Cite This Study

AlRashidi et al. (Tue,) studied this question.

synapsesocial.com/papers/69fadad703f892aec9b1e777 https://doi.org/https://doi.org/10.31083/ijp49432

Bookmark

View Full Paper