scholarly journals Current data on the effectiveness of gliclazide and molecular mechanisms of action of the drug

2020 ◽  
Vol 23 (4) ◽  
pp. 357-367
Author(s):  
Nina A. Petunina ◽  
Irina A. Kuzina ◽  
Ludmila V. Nedosugova
Keyword(s):  
Molecular Mechanisms ◽  
Cardiovascular Complications ◽  
Current Data ◽  
Limiting Factors ◽  
Hypoglycemic Agents ◽  
Oral Hypoglycemic Agents ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Glucagon Like Peptide 1 ◽  
Extrapancreatic Effects

With the growing prevalence of type 2 diabetes mellitus (T2DM) the possibility of treating it with available drugs is one of the main issues. Although glycemic control and reduction of micro- and macrovascular outcomes remain important aspects of treatment, the main limiting factors are the availability and cost of oral hypoglycemic agents. Although newer agents, such as sodium -glucose cotransporter 2 inhibitors, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide 1 receptor agonists, potentially being valuable for patients with insulin resistance and cardiovascular complications, they are relatively expensive and have limited availability. Second-generation sulfonylureas effectively reduce glycated hemoglobin and contribute to the prevention of micro- and macrovascular complications of T2DM The review substantiates the role of Gliclazide MR as a more affordable drug for the treatment of T2DM, the safety of which has been confirmed by many studies; cardio-and nephroprotective effects are shown, as well as mechanisms for influencing в-cells of the pancreas and extrapancreatic effects through activation of phospholipase C and the G-protein-сoupled-receptors (GPCR) are analyzed. The latest data on the assessment of adverse events of Gliclazide MR are presented in comparison with both other sulfonylureas and glucose-lowering drugs of other classes.

scholarly journals Hypoglycemic Coma in a Hemodialysis Patient Receiving Blood Glucose-Lowering Therapy With the Single Agent Teneligliptin

2018 ◽  
Vol 11 ◽  
pp. 117954761876335 ◽  
Author(s):  
Takumi Minezumi ◽  
Shin-ichi Takeda ◽  
Yusuke Igarashi ◽  
Kentaro Sato ◽  
Yoshiaki Murakami ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Single Agent ◽  
Severe Hypoglycemia ◽  
Dipeptidyl Peptidase ◽  
Hypoglycemic Agents ◽  
Tolerability Profile ◽  
Oral Hypoglycemic Agents ◽  
Dipeptidyl Peptidase 4 ◽  
Hypoglycemic Coma ◽  
Dipeptidyl Peptidase 4 Inhibitors

Blood glucose management in patients undergoing dialysis is clinically challenging. In this population, most conventional oral hypoglycemic agents are contraindicated, especially from the perspective of pharmacokinetics. Dipeptidyl peptidase-4 inhibitors exert unique pharmacologic actions via glucose-dependent mechanism and have an excellent tolerability profile with a very low risk of hypoglycemia. Furthermore, the literature reports that some dipeptidyl peptidase-4 inhibitors such as teneligliptin can be administered at the usual dose, regardless of a patient’s level of renal impairment. In this article, we report a case of hypoglycemic coma with a blood glucose level of 23 mg/dL. The patient became fully conscious shortly after receiving a glucose injection; however, severe hypoglycemia recurred for approximately 1.5 days. It eventually disappeared on the discontinuation of teneligliptin, which was the only antidiabetic agent that he had received. The present case may provide deep insights into promoting the safe use of hypoglycemic agents in patients undergoing dialysis.

scholarly journals Evaluation of Hypoglycaemic Effects of Dipeptidyl Peptidase–4 Inhibitors and Biguanide on Type-2 Diabetic subjects: A six months trial

2020 ◽  
Vol 24 (4) ◽  
pp. 368-373
Author(s):  
Naghma Ms. ◽  
Sadia M Azam Khan ◽  
Atta Ullah Khan ◽  
Zahoor Ahmed ◽  
Muhammad Umar ◽  
...  
Keyword(s):  
Venous Blood ◽  
Hypoglycemic Agents ◽  
Dietary Control ◽  
Oral Hypoglycemic Agents ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Group A ◽  
Group B ◽  
Type 2 Diabetic

Objective: This trial was conducted to evaluate the effectiveness of oral hypoglycemic agents on diabetic control and biochemical parameters of known diabetic subjects. Introduction:  T2DM   occurs due to abnormal metabolism of carbohydrate, proteins and lipids leading to increased blood glucose characterized by polyuria and polydypsia due to relative 5deficiency or lack of insulin. Beside dietary control and insulin therapy, various oral hypoglycemic such as sulfonylurea biguanide, thiazolidinedione, DPP–4 inhibitors, glucagon–like peptide inhibitors and SGL2.   Material and Methods: This comparative trial was carried out on previously diagnosed type–2 diabetic subjects. This trial was conducted at health care centers of District Nowshehra viz. NMC Nowshehra, DHQ Hospital Nowshehra, and ICS, Peshawar in collaboration with KMC and PIMC Peshawar, Khyber Pakhtunkhwa, Pakistan. A total of 200 known diabetic subjects were randomly recruited on the basis of predetermined selection criteria and were splited into two groups. Group A having 100 diabetic subjects was given DPP–4 inhibitor; Sitagliptin 50 mg two times a day alone for six (06) months while Group B comprising of 100 patients were treated   with combination of DPP–4 inhibitor (Sitagliptin 50 mg 1BD) and Metformin in a dose of 500 mg two times a day. Venous blood samples were taken from each patient in both fasting (10–12 hour night long fast) and random (2 hour post prandial) state. FBS, RBS, HbA1C, S. creatinine and fasting S. lipid profile were determined by using spectrophotometric colorimetric methods using kits (procured from Elitech, Spain) at  03 and 06 months follow up. Inclusion criteria was subjects with T2DM of age 18 years and above. T2DM patients on insulin, diabetic nephropathy and retinopathy were excluded. The data was analyzed by using SPSS software version 20. Results: Significant results (p < 0.05) were seen for glycemic control (FBS, RBS, HbA1C) in Group B as compare to Group A patients.

scholarly journals Diabetes Mellitus and Colon Carcinogenesis: Expectation for Inhibition of Colon Carcinogenesis by Oral Hypoglycemic Drugs

2019 ◽  
Vol 1 (2) ◽  
pp. 273-289 ◽  
Author(s):  
Junichi Kato ◽  
Yohei Shirakami ◽  
Masahito Shimizu
Keyword(s):  
Diabetes Mellitus ◽  
Colorectal Cancer ◽  
Colon Carcinogenesis ◽  
Basic Research ◽  
Hypoglycemic Agents ◽  
Oral Hypoglycemic Agents ◽  
Antitumor Effects ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Oral Hypoglycemic Drugs

The global deaths due to colorectal cancer and diabetes mellitus have increased by 57% and 90%, respectively. The relationship between various cancers and diabetes mellitus has been shown in multiple epidemiological studies. Hence, better management of diabetes mellitus is expected to reduce the risk of various cancers. This review focuses on colorectal cancer and aims to summarize recent findings on the antitumor effects of various oral hypoglycemic drugs on colorectal cancer and their estimated mechanisms. Of the seven classes of oral hypoglycemic agents, only metformin was found to have suppressive effects on colorectal cancer in both clinical and basic research. Clinical and basic researches on suppressing effects of glinides, dipeptidyl peptidase-4 inhibitors, thiazolidinedione, α-glucosidase inhibitors, and sodium glucose cotransporter-2 inhibitors against colon carcinogenesis have been insufficient and have not arrived at any conclusion. Therefore, further research regarding these agents is warranted. In addition, the suppressive effects of these agents in healthy subjects without diabetes should also be investigated.

A Review on the Effects of New Anti-Diabetic Drugs on Platelet Function

2020 ◽  
Vol 20 (3) ◽  
pp. 328-334 ◽  
Author(s):  
Habib Yaribeygi ◽  
Stephen L. Atkin ◽  
Tannaz Jamialahmadi ◽  
Amirhossein Sahebkar
Keyword(s):  
Platelet Function ◽  
Direct Evidence ◽  
Cardiovascular Complications ◽  
Inhibit Platelet Aggregation ◽  
Dipeptidyl Peptidase 4 ◽  
Sodium Glucose Cotransporter ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Cardiovascular Benefit

Background: Cardiovascular complications account for the majority of deaths caused by diabetes mellitus. Platelet hyperactivity has been shown to increase the risk of thrombotic events and is a therapeutic target for their prevention in diabetes. Modulation of platelet function by diabetes agents in addition to their hypoglycemic effects would contribute to cardiovascular protection. Newly introduced antidiabetic drugs of sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors may have anti-platelet effects, and in the case of SGLT2i and GLP-1RA may contribute to their proven cardiovascular benefit that has been shown clinically. Objective: Here, we reviewed the potential effects of these agents on platelet function in diabetes. Results and Conclusion: GLP-1RA and DPP-4i drugs have antiplatelet properties beyond their primary hypoglycemic effects. Whilst we have little direct evidence for the antiplatelet effects of SGLT2 inhibitors, some studies have shown that these agents may inhibit platelet aggregation and reduce the risk of thrombotic events in diabetes.

Mitochondrial dysfunction plays a key role in the development of neurodegenerative diseases in diabetes

2020 ◽  
Vol 318 (5) ◽  
pp. E750-E764 ◽  
Author(s):  
Han Cheng ◽  
Xiaokun Gang ◽  
Yujia Liu ◽  
Gang Wang ◽  
Xue Zhao ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Reactive Oxygen Species Generation ◽  
Hypoglycemic Agents ◽  
Neuroprotective Effects ◽  
Mitochondrial Dysfunctions ◽  
Dipeptidyl Peptidase 4 ◽  
Beneficial Effects ◽  
Glucagon Like Peptide 1

Mitochondria have an essential function in cell survival due to their role in bioenergetics, reactive oxygen species generation, calcium buffering, and other metabolic activities. Mitochondrial dysfunctions are commonly found in neurodegenerative diseases (NDs), and diabetes is a risk factor for NDs. However, the role of mitochondria in diabetic neurodegeneration is still unclear. In the present study, we review the latest evidence on the role of mitochondrial dysfunctions in the development of diabetes-related NDs and the underlying molecular mechanisms. Hypoglycemic agents, especially metformin, have been proven to have neuroprotective effects in the treatment of diabetes, in which mitochondria could act as one of the underlying mechanisms. Other hypoglycemic agents, including thiazolidinediones (TZDs), dipeptidyl peptidase 4 (DPP-4) inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists, have gained more attention because of their beneficial effects on NDs, presumably by improving mitochondrial function. Our review highlights the notion that mitochondria could be a promising therapeutic target in the treatment of NDs in patients with diabetes.

scholarly journals Cross Referencing 2D-LC Determination of Intact Gliptins in Urine

2020 ◽  
Vol 58 (10) ◽  
pp. 907-914
Author(s):  
Amal M Mohamad ◽  
Cenk A Andac ◽  
Sena Caglar Andac
Keyword(s):  
Urine Samples ◽  
Hypoglycemic Agents ◽  
Therapeutic Drug ◽  
Two Dimensional ◽  
Oral Hypoglycemic Agents ◽  
Online Spe ◽  
Dipeptidyl Peptidase 4 ◽  
Wide Range ◽  
Dipeptidyl Peptidase 4 Inhibitors

Abstract Dipeptidyl peptidase-4 inhibitors, so-called gliptins, constitute a fairly novel class of oral hypoglycemic agents. The development and validation of an automated online SPE-LC-UV method to determine intact sitagliptin, saxagliptin, vildagliptin and metformin simultaneously in human urine samples were performed. For the two-dimensional chromatographic separation, a Gemini C18 (250.0 × 4.6 mm i.d., 110 A0, 5.0 μ) analytical column and a gradient elution with 10.0 mM o-phosphoric acid and methanol and for the online SPE analysis of urine samples, a LiChrospher® ADS SPE-column (20.0 mm × 2.0 mm i.d., 25.0 μm) were used through the study. The fractionation, transfer, elution and separation of the spiked urine samples were achieved in just 9.57 min runtime with 12.0 mL of solvent consumption which was green and economical compared to other sample preparation methods. The calibration curves were determined to be linear in a wide range of 0.10–100.00 μg/mL with satisfactory regression coefficients. Method developed for two-dimensional determination of gliptins would be useful as a reference in therapeutic drug monitoring and screening for forensic medical cases which involve the abuse, unintentional or misuse of multiple gliptins in terms of its practical use, easy detection and reliable results.

scholarly journals The Place of Dipeptidyl Peptidase-4 Inhibitors in Type 2 Diabetes Therapeutics: A “Me Too” or “the Special One” Antidiabetic Class?

2015 ◽  
Vol 2015 ◽  
pp. 1-28 ◽  
Author(s):  
Ricardo Godinho ◽  
Cristina Mega ◽  
Edite Teixeira-de-Lemos ◽  
Eugénia Carvalho ◽  
Frederico Teixeira ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Therapeutic Potential ◽  
Dipeptidyl Peptidase ◽  
Cardiovascular Complications ◽  
Minimal Risk ◽  
Dipeptidyl Peptidase 4 ◽  
Good Glycaemic Control ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Glucagon Like Peptide 1

Incretin-based therapies, the most recent therapeutic options for type 2 diabetes mellitus (T2DM) management, can modify various elements of the disease, including hypersecretion of glucagon, abnormal gastric emptying, postprandial hyperglycaemia, and, possibly, pancreaticβcell dysfunction. Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) increase glucagon-like peptide-1 (GLP-1) availability and correct the “incretin defect” seen in T2DM patients. Clinical studies have shown good glycaemic control with minimal risk of hypoglycaemia or any other adverse effects, despite the reports of pancreatitis, whose association remains to be proved. Recent studies have been focusing on the putative ability of DPP-4 inhibitors to preserve pancreas function, in particular due to the inhibition of apoptotic pathways and stimulation ofβcell proliferation. In addition, other cytoprotective effects on other organs/tissues that are involved in serious T2DM complications, including the heart, kidney, and retina, have been increasingly reported. This review outlines the therapeutic potential of DPP-4 inhibitors for the treatment of T2DM, focusing on their main features, clinical applications, and risks, and discusses the major challenges for the future, in particular the possibility of becoming the preferred therapy for T2DM due to their ability to modify the natural history of the disease and ameliorate nephropathy, retinopathy, and cardiovascular complications.

scholarly journals Antioxidative Potentials of Incretin-Based Medications: A Review of Molecular Mechanisms

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Habib Yaribeygi ◽  
Mina Maleki ◽  
Thozhukat Sathyapalan ◽  
Tannaz Jamialahmadi ◽  
Amirhossein Sahebkar
Keyword(s):  
Oxidative Stress ◽  
Diabetic Complications ◽  
Molecular Mechanisms ◽  
Metabolic Effects ◽  
Therapeutic Effects ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Pharmacologic Agents

Glucagon-like peptide 1 receptor agonists and dipeptidyl-peptidase 4 inhibitors are medications used for managing diabetes, mimicking the metabolic effects of incretin hormones. Recent evidence suggests that these medications have antioxidative potentials in the diabetic milieu. The pathophysiology of most diabetic complications involves oxidative stress. Therefore, if incretin-based antidiabetic medications can alleviate the free radicals involved in oxidative stress, they can potentially provide further therapeutic effects against diabetic complications. However, the molecular mechanisms by which these medications protect against oxidative stress are not fully understood. In the current review, we discuss the potential molecular mechanisms behind these pharmacologic agents’ antioxidative properties.

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