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Glucagon-like Peptide-1 (GLP-1) receptor agonists (GLP-1RAs) emerged as a primary treatment for type-2 diabetes mellitus (T2DM), however, their multifaceted effects on various target organs beyond glycemic control opened a new era of treatment. We conducted a comprehensive literature search using databases including Scopus, Google Scholar, PubMed, and the Cochrane Library to identify clinical, in-vivo, and in-vitro studies focusing on the diverse effects of GLP-1 receptor agonists. Eligible studies were selected based on their relevance to the varied roles of GLP-1RAs in T2DM management and their impact on other physiological functions. Numerous studies have reported the efficacy of GLP-1RAs in improving outcomes in T2DM, with demonstrated benefits including glucose-dependent insulinotropic actions, modulation of insulin signaling pathways, and reductions in glycemic excursions. Additionally, GLP-1 receptors are expressed in various tissues and organs, suggesting their widespread physiological functions beyond glycemic control potentially include neuroprotective, anti-inflammatory, cardioprotective, and metabolic benefits. However, further scientific studies are still underway to maximize the benefits of GLP-1RAs and to discover additional roles in improving health benefits. This article sought to review not only the actions of GLP1RAs in the treatment of T2DM but also explore its effects on potential targets in other disorders. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) is a long-term condition marked by high blood glucose levels caused by insulin resistance which will lead to complications of other diseases such as dyslipidemia, which also affects the health of the liver and kidneys. Butterfly pea flower (Clitorea ternatea L.) has phenolic and flavonoid compounds which have the potential as herbal medicines for antidiabetics. Aim: The purpose of this study is to examine the potential of butterfly pea flower extract (BPE) as an antidiabetic, anti-dyslipidemia, and renoprotection. Methods: In vivo test was performed on Sprague Dawley rats (Rattus norvegicus L.) induced by Streptozotocin-Nicotinamide and High Fat Diet-Propylthiouracil as models of DM and dyslipidemia, and BPE was administered orally (200, 400, and 800 mg/kg BW) for 28 days. glutathione peroxidase (GSH-Px), glutathione S-transferase (GST), tumor necrosis factor-a (TNF-a), nuclear factor-kappa beta (NF-kB), alkaline phosphatase (ALP), liver albumin levels, serum blood urea nitrogen (BUN), serum creatinine, and serum uric acid (UA), were measured by ELISA and colorimetry methods. Results: Treatment of BPE 800 mg/kg BW increased levels of GSH-Px, GST, albumin, and serum protein. BPE decreased TNF-a, NF-kB, and ALP. BPE also decreased BUN, serum CR, and serum UA. Conclusion: BPE has the potential to be used as a drug alternative for the treatment of DM and dyslipidemia as well as a hepatoprotective and renoprotective agent. [ABSTRACT FROM AUTHOR]

Sodium-glucose co-transporter 2 inhibitors (SGLT2is) are recommended as the next step therapy for the management of diabetes mellitus. The large clinical trials of SGLT2is demonstrated benefits on various renal endpoints. We conducted this meta-analysis of large trials on cardiovascular and renal safety trials to explore the renoprotective effect of this group of drugs. PubMed, Cochrane CENTRAL, and EMBASE databases were searched with specific keywords till January 19, 2021. Randomized trials of SGLT2is that evaluated the cardiovascular or renal composite outcome as a primary outcome measure were eligible. Random-effects model was used to calculate the overall risk ratios. The search yielded 716 studies and 10 studies were included. The SGLT2is reduced the risk of composite renal outcome (risk ratio [RR] = 0.64, 95% confidence interval [CI] = 0.58-0.72), decline in estimated glomerular filtration rate (eGFR) (RR = 0.62, 95% CI = 0.50-0.77), doubling of serum creatinine (RR = 0.67, 95% CI = 0.56-0.81), dialysis or renal replacement therapy (RR = 0.71, 95% CI = 0.59-0.86), sustained eGFR of <15 ml per min per 1.73 m2 for at least 30 days or more (RR = 0.66, 95% CI = 0.55-0.81), end-stage renal disease (RR = 0.70, 95% CI = 0.56-0.87), and acute kidney injury (RR = 0.79, 95% CI = 0.71-0.89). This analysis establishes the renoprotective effect of SGLT2is. This benefit is noted in patients who had eGFR of more or <60 ml per min per 1.73 m2. This benefit was uniform across all the SGLT2 inhibitors except ertugliflozin and sotagliflozin. [ABSTRACT FROM AUTHOR]

The objective of this review article was to identify and examine current evidence surrounding the potential renoprotective effects of newer antidiabetic agents such as sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucose-like peptide 1 (GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors. A literature search of MEDLINE and PubMed (January 2000 to April 2019) was performed using the following search terms: "diabetes treatment," "renoprotection," "kidneys," "SGLT-2 inhibitors," "GLP-1 receptor agonists," "DPP-4 inhibitors," and the drug names in each of those classes as well as any combination of these terms. Literature was excluded if published in a language other than English, performed in nonhuman subjects, did not include patients from the United States, was nonrandomized, or the data were available from poster presentations. There were 11 studies that met the search criteria. The majority of the studies focused on renal outcomes as secondary end points and looked at albuminuria, estimated glomerular filtration rate changes from baseline, urinary albumin-to-creatinine ratio, serum creatinine, and need for renal replacement therapy. There are fewer studies that focused on renal protection as a primary end point. After reviewing the available literature, the use of SGLT-2 inhibitors and GLP-1 agonists in addition to standard of care may be considered in patients with or at risk of developing chronic kidney disease. SGLT-2 inhibitors and GLP-1 agonists should be considered when patients' diabetes is no longer well controlled with metformin. Other factors such as cost, cardiovascular disease, and other comorbidities may also be taken into consideration when recommending therapy for patients. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is associated with complications in several different systems of the body, and the incidence of diabetes is rapidly increasing worldwide. The objective of the present study was to evaluate the effect of aqueous extract of Cydonia oblonga Mill. fruit on lipid profile and some biochemical parameters in streptozotocin-induced diabetic rats. The extract showed antihyperlipidemic activity as evidenced by significant decreases in serum triglyceride, total cholesterol, and low density lipoprotein cholesterol (LDL-C) levels along with the elevation of high density lipoprotein cholesterol (HDL-C) in the diabetic rats. The biochemical liver functional tests were also analyzed and it was shown that serum biomarkers of liver dysfunction, including alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were significantly reduced in aqueous extract of Cydonia oblonga Mill. treated diabetic rats. In addition, our results showed that the oral administration of the extract prevented diabetes-induced increase in serum urea and creatinine levels as the markers of renal dysfunction. In conclusion, the present study indicates that aqueous extract of Cydonia oblonga Mill. is able to improve some of the symptoms associated with diabetes and possesses hypolipidemic, hepatoprotective, and renoprotective effects in streptozotocin-induced diabetic rats. [ABSTRACT FROM AUTHOR]

Objective: Aged garlic extract (AGE) has been proven to exhibit antioxidant, hypolipidemic, hypoglycemic and antidiabetic properties. However, its effect on diabetic nephropathy was unexplored. Therefore, the present study was designed to investigate the renoprotective effect of AGE in streptozotocin-induced diabetic rats. Materials and Methods: Albino Wistar rats were induced with diabetes by a single intraperitoneal injection of 45 mg/kg b.w. of streptozotocin. Commercially available AGE was supplemented orally at a dose of 500 mg/kg body weight/day. Aminoguanidine, which has been proven to be an anti-glycation agent was used as positive control and was supplemented at a dose of 1 g/L in drinking water. The serum and urinary biochemical parameters were analyzed in all the groups and at the end of 12 weeks follow up, the renal histological examination were performed using H & E and PAS staining. Results: The diabetic rats showed a significant change in the urine (P < 0.001) and serum (P < 0.01) constituents such as albumin, creatinine, urea nitrogen and glycated hemoglobin. In addition, the serum lipid profile of the diabetic rats were altered significantly (P < 0.05) compared to that of the control rats. However, the diabetic rats supplemented with aged garlic extract restored all these biochemical changes. The efficacy of the extract was substantiated by the histopathological changes in the kidney. Conclusion: From our results, we conclude that aged garlic extract has the ability to ameliorate kidney damage in diabetic rats and the renoprotective effect of AGE may be attributed to its anti-glycation and hypolipidemic activities. [ABSTRACT FROM AUTHOR]