Administration Of Antidiabetic Drugs Research Articles

Activity Test of Cassia alata L. Leaf Extract on Kidney Histopathology Damage Score of Diabetes Mellitus Model

Diabetic nephropathy is a disease experienced by diabetic patients. In this disease, damage to the glomerulus occurs. The administration of antidiabetic drugs tends to cause unwanted side effects, so there is a need for alternative treatment from herbs, one of which is Cassia alata L. Cassia alata L. leaves have chemical content such as flavonoids, alkaloids, tannins, and saponins. Flavonoids reduce blood glucose levels by increasing insulin secretion and mimetic agents, tannins slow carbohydrate digestion and saponins repair pancreatic beta cells and increase glycogen in the liver. This study aims to determine the effect of Cassia alata L. ethanol on the histopathology damage score of male white rat kidney (Rattus norvegicus) induced by streptozotocin. The test animals used were 30 male white rats divided into six treatment groups, each group consisting of five male white rats, namely the normal control group, negative control group, positive control group, treatment group with doses of 500 mg/kg BW, 600 mg/kg BW, and 700 mg/kg BW. The parameters evaluated were kidney tissue damage score and histopathology image analysis. The results showed that the ethanol extract of Cassia alata L. leaves contain alkaloids, flavonoids, saponins, and tannins. The ethanol extract of Cassia alata L. leaves in doses of 500 mg/kg BW, 600 mg/kg BW and 700 mg/kg BW has the activity of reducing the score of kidney tissue damage in male white rats and a dose of 700 mg/kg BW is the best dose in reducing the score of kidney tissue damage in diabetes mellitus models with a score of 2.

New insights into nanomedicines for oral delivery of glucagon-like peptide-1 analogs.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder that arises when the body cannot respond fully to insulin, leading to impaired glucose tolerance. Currently, the treatment embraces non-pharmacological actions (e.g., diet and exercise) co-associated with the administration of antidiabetic drugs. Metformin is the first-line treatment for T2DM; nevertheless, alternative therapeutic strategies involving glucagon-like peptide-1 (GLP-1) analogs have been explored for managing the disease. GLP-1 analogs trigger insulin secretion and suppress glucagon release in a glucose-dependent manner thereby, reducing the risk of hyperglycemia. Additionally, GLP-1 analogs have an extended plasma half-life compared to the endogenous peptide due to their high resistance to degradation by dipeptidyl peptidase-4. However, GLP-1 analogs are mainly administered via subcutaneous route, which can be inconvenient for the patients. Even considering an oral delivery approach, GLP-1 analogs are exposed to the harsh conditions of the gastrointestinal tract (GIT) and the intestinal barriers (mucus and epithelium). Hereupon, there is an unmet need to develop non-invasive oral transmucosal drug delivery strategies, such as the incorporation of GLP-1 analogs into nanoplatforms, to overcome the GIT barriers. Nanotechnology has the potential to shield antidiabetic peptides against the acidic pH and enzymatic activity of the stomach. In addition, the nanoparticles can be coated and/or surface-conjugated with mucodiffusive polymers and target intestinal ligands to improve their transport through the intestinal mucus and epithelium. This review focuses on the main hurdles associated with the oral administration of GLP-1 and GLP-1 analogs, and the nanosystems developed to improve the oral bioavailability of the antidiabetic peptides. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Associations of antidiabetic drugs with diabetic retinopathy in people with type 2 diabetes: an umbrella review and meta-analysis.

Diabetic retinopathy (DR) is the most frequent complication of type 2 diabetes and remains the leading cause of preventable blindness. Current clinical decisions regarding the administration of antidiabetic drugs do not sufficiently incorporate the risk of DR due to the inconclusive evidence from preceding meta-analyses. This umbrella review aimed to systematically evaluate the effects of antidiabetic drugs on DR in people with type 2 diabetes. A systematic literature search was undertaken in Medline, Embase, and the Cochrane Library (from inception till 17th May 2022) without language restrictions to identify systematic reviews and meta-analyses of randomized controlled trials or longitudinal studies that examined the association between antidiabetic drugs and DR in people with type 2 diabetes. Two authors independently extracted data and assessed the quality of included studies using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) checklist, and evidence assessment was performed using the GRADE (Grading of recommendations, Assessment, Development and Evaluation). Random-effects models were applied to calculate relative risk (RR) or odds ratios (OR) with 95% confidence intervals (CI). This study was registered with PROSPERO (CRD42022332052). With trial evidence from 11 systematic reviews and meta-analyses, we found that the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), or dipeptidyl peptidase-4 inhibitors (DPP-4i) was not statistically associated with the risk of DR, compared to either placebo (RR: GLP-1 RA, 0.98, 0.89-1.08; SGLT-2i, 1.00, 95% CI 0.79-1.27; DPP-4i, 1.17, 0.99-1.39) or other antidiabetic drugs. Compared to other antidiabetic drugs, meglitinides (0.34, 0.01-8.25), SGLT-2i (0.73, 0.10-5.16), thiazolidinediones (0.92, 0.67-1.26), metformin (1.15, 0.81-1.63), sulphonylureas (1.24, 0.93-1.65), and acarbose (4.21, 0.44-40.43) were not statistically associated with the risk of DR. With evidence from longitudinal studies only, insulin was found to have a higher risk of DR than other antidiabetic drugs (OR: 2.47, 95% CI: 2.04-2.99). Our results indicate that antidiabetic drugs are generally safe to prescribe regarding the risk of DR among people with type 2 diabetes. Further robust and large-scale trials investigating the effects of insulin, meglitinides, and acarbose on DR are warranted. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=332052, identifier CRD42022332052.

Effect of anti-diabetic drugs in dialysis patients with diabetes: a nationwide retrospective cohort study

BackgroundType 2 diabetes mellitus is common in patients undergoing dialysis. However, the association between anti-diabetic drug use and survival outcomes is rarely discussed. We aimed to investigate whether continued anti-diabetic medication use affects the survival of diabetic dialysis patients and whether different hypoglycemic drug use influences prognosis.MethodsUsing a nationwide database, we enrolled patients with incident end-stage renal disease under maintenance dialysis during 2011–2015 into the pre-existing diabetes dialysis (PDD), incident diabetes after dialysis (IDD), and non-diabetic dialysis (NDD) groups. The PDD group was further subclassified into patients who continued (PDD-M) and discontinued (PDD-NM) anti-diabetic drug use after dialysis.ResultsA total of 5249 dialysis patients were examined. The PDD-NM group displayed a significantly higher mortality rate than the IDD, PDD-M, and NDD groups (log-rank test P < 0.001). The PDD-M group had a significantly lower risk of death, regardless of insulin (P < 0.001) or oral hypoglycemic agent (OHA) (P < 0.001) use. Initial insulin administration or OHA had no statistically significant effect on overall mortality in the IDD group. But OHA use had better survival trends than insulin administration for the older (P = 0.02) and male subgroups (P = 0.05).ConclusionsFor dialysis patients with diabetes, continuous administration of anti-diabetic drugs after dialysis and choice of medication may affect outcomes.

Pericapillary basement membrane thickening in human skeletal muscles.

The basement membrane (BM) surrounding capillaries in skeletal muscles varies physiologically in thickness according to age, physical fitness, and anatomical site in humans. Furthermore, the pericapillary BM thickness (CBMT) increases pathophysiologically during several common disease states, including peripheral arterial disease and diabetes mellitus. This review on CBM thickening in human skeletal muscles is two pronged. First, it addresses the advantages/disadvantages of grid- and tablet-based measuring and morphometric techniques that are implemented to assess the CBMT on transmission electron micrographs. Second, it deals with the biology of CBM thickening in skeletal muscles, particularly its possible causes, molecular mechanisms, and functional impact. CBM thickening is triggered by several physical factors, including diabetes-associated glycation, hydrostatic pressure, and inflammation. Increased biosynthesis of type IV collagen expression or repetitive cycles in pericyte or endothelial cell degeneration/proliferation appear to be most critical for CBM accumulation. A thickened CBM obviously poses a greater barrier for diffusion, lowers the microvascular elasticity, and impedes transcytosis of inflammatory cells. Our own morphometric data reveal the CBM enlargement to be not accompanied by the pericyte coverage. Owing to an overlap or redundancy in the capillary supply, CBM thickening in skeletal muscles might not be such a devastating occurrence as in organs with endarterial circulation (e.g., kidney and retina). CBM growth in skeletal muscles can be reversed by training or administration of antidiabetic drugs. In conclusion, CBM thickening in skeletal muscles is a microvascular remodeling process by which metabolic, hemodynamic, and inflammatory forces are integrated together and which could play a hitherto underestimated role in etiology/progression of human diseases.

Awareness and administration of antidiabetic drugs in patients with diabetes in Huairou district of Beijing

Objective To investigate the awareness and administration of antidiabetic drugs in patients with diabetes in Huairou district of Beijing. Methods A questionnaire survey on knowledge and administration of antidiabetic drugs were conducted in 900 diabetic patients from 16 communities in Huairou district of Beijing from November 2014 to February 2015. The related factors influencing antidiabetic drug use were analyzed with logistic regression method. Results A total of 899 questionnaires were recovered. Results showed that the rate of metformin single use was the highest (23.7%, 213/899), the rate of combination use of metformin and acarbose was 11.8%(106/899), and that of metformin and glipizide was 17.1% (154/899). Survey showed that 65.9% (592/899) patients were compliant immediately for antidiabetic agents, 32.2% (290/899) were not immediately compliant, 1.9% (17/899) did not use antidiabetic agents. Logistic regression analysis showed that the factors affecting the use of antidiabetic agents were the types of medication (t=-4.351, P=0.000) , adverse effects of drugs (t=6.999, P=0.000), awareness of diabetes to health hazard (t=-10.969, P=0.000) and the doctor's recommendation (t=-3.352, P=0.001). Conclusion The results showed that the administration of antidiabetic drugs in diabetic patients from Huairou district is basically followed the recommendation by 2013 edition of type 2 diabetes guidelines and the compliance rate of medication need to be further raised. Key words: Diabetes mellitus; Hypoglycemic agents; Cognition

Studies on the Effect of Antidiabetic Drugs on Collagen in Rats

To assess the effects of antidiabetic drugs on collagen, the study has been carried out. However, at present, no conclusive data available on the In vivo effect of antidiabetic drugs in collagen. It was therefore thought worthwhile to undertake a systemic study on the metabolic turnover of connective tissue proteins, particularly collagen which will help to understand the various changes taking place in conventional antidiabetic drug treated rats. The hydroxyproline content was determined by the method of Neumann and Logan. There was no significant difference in mean body weight of animals in treated groups when compared to control animals on 50th day. In drug treated group G5, urinary excretion of hydroxyproline was slightly increased in contrast to that of the rats in other groups and showed a significant difference (p < 0.001) between control and G5 group. The proportion of soluble collagen in treated group was somewhat higher than in the control but while taking the significance value there are no statistically significant changes. Liver showed the highest concentration of 0.98 g collagen/100 g tissue, whereas kidney and heart showed 0.57 and 0.72 g collagen/100 g tissue. Observations of the present study collectively indicate that the anabolic rate of collagen metabolism is not altered significantly by the administration of antidiabetic drugs in normal rats.

Effects of three antidiabetics on insulin and leptin in Chinese type 2 diabetes

Aims This study was to investigate the effects of some different antidiabetics on circulating insulin and leptin levels in type 2 diabetes with or without overweight in a Chinese population. Methods 80 type 2 diabetes men with overweight (body mass index BMI > 24 kg/m 2) and 35 type 2 diabetes men with normal body weight (BMI ≤ 24 kg/m 2) and 56 control subjects were enrolled in the study. We measured blood glucose, insulin, leptin, total cholesterol, LDL-C, HDL-C, triglycerides, fasting glucose, postprandial glycose, HbA1c and BMI before and after the administration of antidiabetic drugs. Results Compared with normal body weight, the levels of plasma insulin and leptin in overweight type 2 diabetes men were higher, after 3 months treatment, a significant increase in insulin and leptin levels was observed in overweight type 2 diabetes men in gliclazide group. Levels of leptin and insulin decreased in metformin and rosiglitazone groups, respectively. Conclusions We conclude that surfonylureas treatment leads to increased insulin and leptin levels in overweight type 2 diabetes men, metformin, or rosiglitazone treatment can reduce insulin and leptin levels, respectively, and effect of metformin on plasma leptin and insulin levels is more significant than that of rosiglitazone.

Effects of Antidiabetic Drugs on Glucose Tolerance in Streptozotocin-nicotinamide-induced Mildly Diabetic and Streptozotocin-induced Severely Diabetic Mice

In this study, streptozotocin-nicotinamide-induced mildly diabetic mice and streptozotocin-induced severely diabetic mice were created to compare their characteristics and to investigate the effects of antidiabetic drugs on glucose tolerance. In severely diabetic mice, the pancreatic insulin content decreased to approximately 10% of levels found in normal mice. These mice also showed a decrease in body weight, a marked increase in nonfasting blood glucose levels and urinary glucose excretion, and a marked decline in glucose tolerance due to insulin secretory deficiency. In contrast, the pancreatic insulin content was approximately 50% of normal levels in mildly diabetic mice. These mice did not show any change in body weight, but displayed a mild increase in nonfasting blood glucose levels and urinary glucose excretion, and a mild decline in glucose tolerance due to loss of early-phase insulin secretion. Administration of antidiabetic drugs, namely voglibose, metformin, glibenclamide, sitagliptin and insulin, significantly improved glucose tolerance in mildly diabetic mice. In severely diabetic mice, voglibose, metformin and insulin significantly improved glucose tolerance, but no significant effect was observed for glibenclamide and sitagliptin due to a decreased insulinotropic effect. These results demonstrate that streptozotocin-nicotinamide-induced mildly diabetic mice have many pathological features resembling type 2 diabetes, and can serve as models for the pharmacological evaluation of many antidiabetic drugs.