scholarly journals Feasibility of Structural Modification of Retinoid X Receptor Agonists to Separate Blood Glucose-Lowering Action from Adverse Effects: Studies in KKAy Type 2 Diabetes Model Mice

2012 ◽  
Vol 35 (4) ◽  
pp. 629-633 ◽  
Author(s):  
Hiroki Kakuta ◽  
Fuminori Ohsawa ◽  
Shoya Yamada ◽  
Makoto Makishima ◽  
Akihiro Tai ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Adverse Effects ◽  
Structural Modification ◽  
Retinoid X Receptor ◽  
Glucose Lowering ◽  
Receptor Agonists ◽  
Diabetes Model

scholarly journals Glycaemic Control in Diabetes

2021 ◽  
Author(s):  
D. Müller-Wieland ◽  
J. Brandts ◽  
M. Verket ◽  
N. Marx ◽  
K. Schütt
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Blood Glucose ◽  
Kidney Disease ◽  
Treatment Guidelines ◽  
Glucose Lowering ◽  
Receptor Agonists ◽  
Cardiovascular Endpoint

AbstractReduction of glucose is the hallmark of diabetes therapy proven to reduce micro- and macro-vascular risk in patients with type 1 diabetes. However glucose-lowering efficacy trials in type 2 diabetes didn’t show major cardiovascular benefit. Then, a paradigm change in the treatment of patients with type 2 diabetes has emerged due to the introduction of new blood glucose-lowering agents. Cardiovascular endpoint studies have proven HbA1c-independent cardioprotective effects for GLP-1 receptor agonists and SGLT-2 inhibitors. Furthermore, SGLT-2 inhibitors reduce the risk for heart failure and chronic kidney disease. Mechanisms for these blood glucose independent drug target-related effects are still an enigma. Recent research has shown that GLP-1 receptor agonists might have anti-inflammatory and plaque stabilising effects whereas SGLT-2 inhibitors primarily reduce pre- and after-load of the heart and increase work load efficiency of the heart. In addition, reduction of intraglomerular pressure, improved energy supply chains and water regulation appear to be major mechanisms for renoprotection by SGLT-2 inhibitors. These studies and observations have led to recent changes in clinical recommendations and treatment guidelines for type 2 diabetes. In patients with high or very high cardio-renal risk, SGLT-2 inhibitors or GLP-1 receptor agonists have a preferred recommendation independent of baseline HbA1c levels due to cardioprotection. In patients with chronic heart failure, chronic kidney disease or at respective risks SGLT-2 inhibitors are the preferred choice. Therefore, the treatment paradigm of glucose control in diabetes has changed towards using diabetes drugs with evidence-based organ protection improving clinical prognosis.

Efficacy and Safety of GLP-1 Receptor Agonists Across the Spectrum of Type 2 Diabetes Mellitus

2017 ◽  
Vol 125 (07) ◽  
pp. 419-435 ◽  
Author(s):  
Lawrence Leiter ◽  
Michael Nauck
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Glucose Lowering ◽  
Receptor Agonists ◽  
Glucagon Like Peptide 1 ◽  
Gastrointestinal Adverse Events

AbstractFor patients with type 2 diabetes mellitus, glucagon-like peptide-1 receptor agonists (GLP-1RAs) generally exert robust glucose-lowering effects that are at least as effective as insulin. As monotherapies, changes from baseline in HbA1c with GLP-1RAs ranged from –1.9 to –0.7% in phase 3 trials. In addition, GLP-1RAs confer a low risk of hypoglycaemia and have a body-weight advantage (changes from baseline ranging from –4.0 to –0.4 kg). There is also evidence of significant reductions in risk for cardiovascular events with some of these agents, with a number of other trials underway. Gastrointestinal adverse events typically increase with GLP-1RAs, although these are generally mild to moderate in intensity and rarely require treatment discontinuation. The GLP-1RAs that are commercially available or in development vary in structure and pharmacokinetics. These differences affect the frequency of administration and can also affect their relative efficacy and safety. This review summarizes the findings of phase 3 glycaemic control trials of available GLP-1RAs and considers them in the context of the distinct clinical needs of individual patients.

Dispensation Patterns of Glucose-Lowering Drugs in Newly Diagnosed Type 2 Diabetes: Routine Data Analysis of Insurance Claims in Germany

2021 ◽  
Author(s):  
Brenda Bongaerts ◽  
Bianca Kollhorst ◽  
Oliver Kuss ◽  
Iris Pigeot ◽  
Wolfgang Rathmann
Keyword(s):  
Type 2 Diabetes ◽  
Diabetes Diagnosis ◽  
Research Database ◽  
Second Line ◽  
Newly Diagnosed ◽  
First Line ◽  
Glucose Lowering ◽  
Receptor Agonists ◽  
Metformin Monotherapy

Abstract Aims To describe dispensation patterns of glucose-lowering drugs in newly diagnosed type 2 diabetes in Germany. Materials and methods Based on claims data from four statutory health insurances (German Pharmacoepidemiological Research Database,>25 million insurants), all individuals with newly diagnosed type 2 diabetes were identified. Eligible patients had a first diagnosis for type 2 diabetes between January 2012 and December 2016. We analyzed the dispensation patterns of first-line glucose-lowering therapies initiated in the year after diabetes diagnosis and patterns of second-line therapies dispensed one year after first-line treatment. Results A total of 356,647 individuals with newly diagnosed type 2 diabetes were included (average age [SD]: 63.5 [13.4] years; 49.3% males). Of the 31.6% of individuals who were pharmacologically treated in the year after diagnosis, metformin monotherapy was most frequently dispensed (73.1%), followed by dual therapy of metformin and dipeptidyl peptidase-4 inhibitors (DPP-4is) (6.4%), and monotherapy with DPP-4is (2.9%). From 2012 through 2016, sulfonylurea dispensations were reduced by more than 50%. Dispensations for combination therapies with DPP-4is increased up to 10.6%. Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors contributed to 2% of all treatments. After a median of 5 months, 20.0% of individuals on pharmacological therapy initiated second-line glucose-lowering treatment. Conclusions Data from German statutory health insurances (2012 to 2016) showed that most individuals with newly diagnosed type 2 diabetes were dispensed metformin monotherapy in line with diabetes care guidelines. A substantial decrease in the use of sulfonylureas was observed after the introduction of DPP-4i and GLP-1 receptor agonists.

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.

Cardiovascular, renal and liver protection with novel antidiabetic agents beyond blood glucose lowering in type 2 diabetes

2020 ◽  
Vol 38 (3) ◽  
pp. 377-386 ◽  
Author(s):  
Vasilios Kotsis ◽  
Jens Jordan ◽  
Stella Stabouli ◽  
Christina Antza ◽  
Dragan Micic ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Antidiabetic Agents ◽  
Glucose Lowering ◽  
Liver Protection
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