Sulfonylureas in today’s blood glucose lowering therapy.New data on advantages and potential barriers of an “old” antidiabetic group

2015 ◽  
Vol 156 (13) ◽  
pp. 511-515
Author(s):  
Gábor Winkler
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Glucose Lowering ◽  
Dipeptidyl Peptidase 4 ◽  
Sulfonylurea Compounds ◽  
Drug Of Choice ◽  
Antidiabetic Treatment ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Glucose Lowering Therapy

Sulfonylurea compounds have been basic elements of antidiabetic treatment in type 2 diabetes for a long time. However, with the introduction of incretin type insulin secretagogues it is often arises, whether is still there a place for sulfonylureas in the today’s therapy. To answer this question the author overviews general pharmaceutical characteristics of the sulfonylurea compounds as well as individual particularities of the second generation derivatives used at present in Hungary. The author details also the most important differences between incretin type drugs − first of all dipeptidyl peptidase-4 inhibitors − and sulfonylureas. On the basis of available data it can be concluded in accordance with the latest international guidelines, that sulfonylureas have still role in the blood glucose lowering therapy of type 2 diabetes, though they became somewhat pushed back among insulin secretagogue type drugs. If a sulfonylurea compound is the drug of choice, it is important to select the appropriate molecule (in case of normal renal function gliclazide or glimepiride). It is also important to re-educate the patient, as well as to apply the minimal dose providing the desired glycaemic effect. Orv. Hetil., 2015, 156(13), 511–515.

scholarly journals Impact of Glucose-Lowering Medications on Cardiometabolic Risk in Type 2 Diabetes

2019 ◽  
Author(s):  
Angelo Maria Patti ◽  
Ali A Rizvi ◽  
Rosaria Vincenza Giglio ◽  
Anca Pantea Stoian ◽  
Daniela Ligi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Subclinical Atherosclerosis ◽  
Macrophage Polarization ◽  
Vascular Complications ◽  
Rapid Progression ◽  
Glucose Lowering ◽  
Dipeptidyl Peptidase 4 ◽  
Antidiabetic Treatment ◽  
Dipeptidyl Peptidase 4 Inhibitors

Type 2 Diabetes Mellitus (T2DM) is associated with a high risk of atherosclerotic cardiovascular (CV) disease. Contributing pathophysiologic factors include endothelial dysfunction caused by excessive production of reactive oxygen species (ROS), increased activity of nuclear factor kB (NFkB), altered macrophage polarization, and reduced synthesis of endothelial progenitor cells (EPC). Consequently, there can be a potentially rapid progression of the atherosclerotic disease with a higher propensity to unstable plaque, leading to increased cardiovascular mortality. Management is aimed at prevention, early diagnosis, and treatment of hyperglycemia and vascular complications. Innovative therapeutic approaches for T2DM seek to customize the antidiabetic treatment to each patient in order to optimize glucose-lowering effects, minimize hypoglycemia and adverse effects, and prevent cardiovascular events. The newer drugs (Glucagon Like Peptide-1 Receptor Agonists, GLP-1 RAs; Sodium GLucose coTransporter-2 inhibitors, SGLT2is; DiPeptidyl Peptidase-4 inhibitors, DPP4is) impact body weight, lipid parameters, and blood pressure, as well as endothelial function, inflammatory markers, markers of oxidative stress, and subclinical atherosclerosis. The present review summarizes the results of trials that evaluated the cardiovascular safety of these drugs and found them to be safe from the CV standpoint.

Pleiotropic effects of incretins and antidiabetics with incretine mechanism

2013 ◽  
Vol 154 (7) ◽  
pp. 248-255 ◽  
Author(s):  
Gábor Winkler
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Blood Lipid ◽  
Point Of View ◽  
Pleiotropic Effects ◽  
Glucose Lowering ◽  
Incretin Mimetics ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors

Discovery of physiological and pharmacological characteristics of incretins (glucagon-like peptide-1 and glucose-dependent insulinotrop polypeptide), and the introduction of various products of those into the clinical practice has fundamentally changed blood glucose lowering therapy in type 2 diabetes. In addition to the antidiabetic properties more attention is paid to their favourable pleiotropic effects independent from the blood glucose lowering such as cardio-, vaso- and renoprotectiv, blood pressure lowering effects, as well as beneficial changes on blood lipid values and hepatic steatosis. These preferential changes prevail in slightly different way when incretin mimetics applied and dipeptidyl peptidase-4 inhibitors, furthermore, prolonged action of peptides metabolised by this enzyme may serve additional benefits in this latter mentioned group. The article overviews the currently known most important pleiotropic effects of incretins from the point of view of cardiorenal risk accompanying type 2 diabetes. Orv. Hetil., 2013, 154, 248–255.

scholarly journals Trust and VERIFY: the role of combined treatment with metformin and dipeptidyl peptidase-4 inhibitors in new-onset diabetes type 2

2020 ◽  
Vol 4 (6) ◽  
pp. 334-339
Author(s):  
T.Yu. Demidova ◽  
◽  
A.A. Kozhevnikov ◽  
Keyword(s):  
Combined Treatment ◽  
Diabetes Type 2 ◽  
Dipeptidyl Peptidase ◽  
Diabetes Type ◽  
Glucose Lowering ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Glucose Lowering Therapy

Diabetes is a progressive disease that manifests itself in hyperglycemia and is associated with macro- and microvascular complications. Stepwise approach to glucose-lowering therapy is now often questioned for two main reasons. First, the decision on intensifying the treatment requires the decompensation of carbohydrate metabolism. Second, this conception does not always meet the criteria of pathophysiological treatment, in particular, in patients who are newly diagnosed with diabetes type 2 and recommended with metformin monotherapy. The combination of metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors is a well-known strategy that effectively controls blood glucose level and preserves beta cell functions. VERIFY study has demonstrated that after a 5-year follow-up, median time to type 2 diabetes decompensation is 36.1 months in metformin group and 61.9 months in early combined treatment group (metformin plus vildagliptin) (p<0.0001). These findings can account for paradigm shift in treatment prescription for newly diagnosed type 2 diabetes in patients with HbA1c less than 1,0% of the target level.KEYWORDS: diabetes, glucose-lowering therapy, control of glycemia, combined treatment.FOR CITATION: Demidova T.Yu., Kozhevnikov A.A. Trust and VERIFY: the role of combined treatment with metformin and dipeptidyl peptidase-4 inhibitors in new-onset diabetes type 2. Russian Medical Inquiry. 2020;4(6):334–339. DOI: 10.32364/2587-6821-2020-4-6-334-339.

scholarly journals Chronic renal disease in patients with type 2 diabetes mellitus

2019 ◽  
Vol 10 (2) ◽  
pp. 65-70 ◽  
Author(s):  
Nane E. Khachaturian
Keyword(s):  
Diabetes Mellitus ◽  
Renal Disease ◽  
Chronic Renal Disease ◽  
Self Monitoring ◽  
Glucose Lowering ◽  
Dipeptidyl Peptidase 4 ◽  
Lowering Therapy ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Glucose Lowering Therapy

Diabetes mellitus (DM) type 2 (type 2 diabetes) is one of the most common non-infectious diseases worldwide. Chronic hyperglycemia is a leading factor in a development of vascular complications of diabetes which involve various organs, particularly the eyes, kidney, cardiovascular system and nervous system. One of the most common complications of DM is diabetic nephropathy. Presence of chronic renal disease in a patient with DM limits options of glucose-lowering therapy. Dipeptidyl peptidase-4 inhibitors are currently among medications of choice for glucose-lowering therapy in patients with chronic renal disease. All currently available dipeptidyl peptidase-4 inhibitors can be administrated to patients with end-stage kidney disease on dialysis, and a rate of their use is continuously increasing. Given a high risk of hypoglycemic conditions in patients with chronic renal disease, a regular self-monitoring of glycemia is an essential component of a treatment. Glucometer Contour Plus One is one of the most recent devices developed for self-monitoring of blood glucose. Its advantage over all other blood glucose meters is an ability to synchronize with a mobile application Contour™ Diabetes (Contour Diabetes).

The efficacy and safety of dipeptidyl peptidase-4 inhibitors compared to other oral glucose-lowering medications in the treatment of type 2 diabetes

Metabolism ◽  
2020 ◽  
Vol 109 ◽  
pp. 154295
Author(s):  
Anca Pantea Stoian ◽  
Alexandros Sachinidis ◽  
Roxana Adriana Stoica ◽  
Dragana Nikolic ◽  
Angelo Maria Patti ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Dipeptidyl Peptidase ◽  
Oral Glucose ◽  
Efficacy And Safety ◽  
Glucose Lowering ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors

scholarly journals Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Luis M. Pérez-Belmonte ◽  
◽  
José David Torres-Peña ◽  
María D. López-Carmona ◽  
M. Mar. Ayala-Gutiérrez ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Adverse Outcomes ◽  
Hospital Death ◽  
Glucose Lowering ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
At Home

Abstract Background Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. Methods We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine’s registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. Results A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. Conclusions In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed.

scholarly journals Impact of Glucose-Lowering Medications on Cardiovascular and Metabolic Risk in Type 2 Diabetes

2020 ◽  
Vol 9 (4) ◽  
pp. 912 ◽  
Author(s):  
Angelo Maria Patti ◽  
Ali A Rizvi ◽  
Rosaria Vincenza Giglio ◽  
Anca Pantea Stoian ◽  
Daniela Ligi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Subclinical Atherosclerosis ◽  
Macrophage Polarization ◽  
Vascular Complications ◽  
Rapid Progression ◽  
Glucose Lowering ◽  
Antidiabetic Treatment ◽  
Dipeptidyl Peptidase 4 Inhibitors

Type 2 Diabetes Mellitus (T2DM) is associated with a high risk of atherosclerotic cardiovascular (CV) disease. Among the well-known pathophysiologic factors, crucial roles are played by endothelial dysfunction (caused by oxidative stress and inflammation hyperglycemia-linked), increased activity of nuclear factor kB, altered macrophage polarization, and reduced synthesis of resident endothelial progenitor cells. As consequence, a potentially rapid progression of the atherosclerotic disease with a higher propensity to unstable plaque is arguable, finally leading to significantly increased cardiovascular mortality. Main managements are focused on both prevention and early diagnosis, by targeted treatment of hyperglycemia and vascular complications. Innovative therapeutic approaches for T2DM seek to customize the antidiabetic treatment to each patient in order to optimize glucose-lowering effects, minimize hypoglycemia and adverse effects, and prevent cardiovascular events. The newer drugs (e.g., Glucagon Like Peptide-1 Receptor Agonists, GLP-1 RAs; Sodium GLucose coTransporter-2 inhibitors, SGLT2is; DiPeptidyl Peptidase-4 inhibitors, and DPP4is) impact body weight, lipid parameters, and blood pressure, as well as endothelial (dys)functions, inflammatory markers, biomarkers of both oxidative stress, and subclinical atherosclerosis. The present review summarizes the results of the main trials focused on the cardiovascular safety of these drugs from the CV standpoint.

scholarly journals Further Possible Mechanisms of Dipeptidyl Peptidase-4 Inhibitors to Decrease Blood Glucose in Subjects with Type 2 Diabetes

2011 ◽  
Vol 2 ◽  
pp. JCM.S8408 ◽  
Author(s):  
Hiroyuki Koshiyama
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Blood Glucose ◽  
Glucagon Secretion ◽  
Dipeptidyl Peptidase ◽  
Dependent Manner ◽  
Dipeptidyl Peptidase 4 ◽  
Stimulate Insulin Secretion ◽  
Dipeptidyl Peptidase 4 Inhibitors

Recently, dipeptidyl peptidase-4 (DPP-4) inhibitors have been launched into clinical use for type 2 diabetes in Japan. Shortly after its use, several cases have been reported, in which the co-administration of DPP-4 inhibitors with sulfonylureas caused severe hyperglycemia in Japan. Additionally, the efficacy to improve glycemic control was greater than expected. Taken together, it is suggested that DPP-4 inhibitors may have other action mechanisms than to stimulate insulin secretion in glucose-dependent manner. I present here several possible mechanisms of DPP-4 inhibitors to reduce blood glucose in type 2 diabetes; first, to inhibit glucagon secretion, second, to stimulate glucose-dependent insulinotropic peptide (GIP) secretion, which may regain its action to stimulate insulin secretion when hyperglycemia has been improved, third, to recover the response to sulfonylureas by restoring pancreatic ATP levels, fourth, to stimulate glucagon-like peptide 1 (GLP-1) secretion directly from the intestine, and finally to inhibit the action of DPP-4 as an adipokine.

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