Fundam Clin Pharmacol. 2022 Feb 2. doi: 10.1111/fcp.12765. Online ahead of print.
ABSTRACT
BACKGROUND: Diabetic dyslipidemia is a significant contributor in the pathogenesis of type 2 diabetes (T2D).
OBJECTIVES: The study aimed at comparing effect of dapagliflozin, liraglutide and atorvastatin alone or their combinations on lipids and inflammatory markers and their vascular impact in T2D rats.
METHODS: 56 male albino rats were included in the study and divided into 2 main groups. Group A (8 rats) served as normal control. Group B (48 rats) were streptozotocin – nicotinamide – induced diabetic rats. Subgroups (B-1, B-2, B-3, B-4, B-5 and B-6) received (no medications, dapagliflozin, liraglutide, atorvastatin, dapagliflozin + atorvastatin and liraglutide + atorvastatin) respectively. Urine albumin/creatinine ratio (UACR), glycosylated hemoglobin (HBA1c), fasting serum glucose (FSG), serum LDL-C, HDL-C, TGs, lipoprotein(a) Lp (a), serum thyrotropin (TSH), highly sensitive C-reactive protein (hs-CRP) and advanced glycation end products (AGEs), were assessed. Qualitative and quantitative histological examination of kidneys focused on renal corpuscles.
RESULTS: Dapagliflozin improved the studied parameters but with statistically insignificant increase in LDL-C, Lp (a) and significant increase in UACR. Atorvastatin improved the studied parameters but with statistically insignificant increase in FSG and HbA1C. Liraglutide and the combination groups significantly improved all studied parameters. Histologically; liraglutide, atorvastatin produced therapeutic effect, while dapagliflozin depicted nephrotoxic effect. Combination groups resulted in better effects with normalization of most of renal corpuscles. There were positive correlations between LDL-C & hs-CRP, AGEs, TSH and mesangial expansion.
CONCLUSION: Combination of atorvastatin with liraglutide can improve its vasculoprotective effect. Moreover, combination of atorvastatin with dapagliflozin can ameliorate its possible nephrotoxic effect.
PMID:35106814 | DOI:10.1111/fcp.12765