GLP-1 receptor agonists have a sustained stimulatory effect on corticosterone release after chronic treatment

2014 ◽  
Vol 27 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Maarja Krass ◽  
Annika Volke ◽  
Kertu Rünkorg ◽  
Gregers Wegener ◽  
Sten Lund ◽  
...  
Keyword(s):  
Chronic Treatment ◽  
Genetic Model ◽  
Anxiety Level ◽  
Dark Compartment ◽  
Antidepressant Effect ◽  
Acute Administration ◽  
Receptor Agonists ◽  
Swimming Stress ◽  
Glucagon Like Peptide 1 ◽  
Corticosterone Release

ObjectiveGlucagon-like peptide 1 (GLP-1) receptor agonists are a new group of antidiabetic medications quickly gaining popularity. We aimed to examine behavioural and neuroendocrine changes following chronic treatment with GLP-1 receptor agonists in animal models.MethodsThe effects of chronic treatment with GLP-1 receptor agonists were determined on behavioural parameters [anxiety level in the light–dark compartment test, the motor activity in automated activity cages, immobility in the forced swimming test (FST)] and on corticosterone release in mice. The possible antidepressant effect of chronic liraglutide treatment was also studied in Flinders Sensitive Line (FSL) rats, a genetic model of depression.ResultsTwo weeks of treatment with exenatide (10 µg /kg twice daily) or liraglutide (1200 µg/kg once daily) did not affect the anxiety level in a light–dark compartment test nor induce an antidepressant-like effect in the FST in mice. Moreover, chronic treatment with liraglutide had no effect on depression-related behaviour in FSL rats. Interestingly, hypolocomotion induced by the drugs in mice disappeared after chronic dosing. Both of the GLP-1 receptor agonists induced robust increases in corticosterone levels in mice under basal conditions as well as in the case of combination with swimming stress. Remarkably, exenatide was as potent a stimulator of corticosterone release after 2 weeks as after acute administration.ConclusionsThe increases in corticosterone release seen after acute exenatide or liraglutide treatment do not abate after 2 weeks of treatment demonstrating that tolerance does not develop towards this particular effect of GLP-1 agonists.

Acute administration of GLP-1 receptor agonists induces hypolocomotion but not anxiety in mice

2012 ◽  
Vol 24 (5) ◽  
pp. 296-300 ◽  
Author(s):  
Maarja Krass ◽  
Kertu Rünkorg ◽  
Eero Vasar ◽  
Vallo Volke
Keyword(s):  
Motor Activity ◽  
Anxiety Level ◽  
Acute Administration ◽  
Hormonal Effects ◽  
Receptor Agonists ◽  
Glucose Levels ◽  
Immobility Time ◽  
Swimming Test ◽  
Glucagon Like Peptide 1 ◽  
Corticosterone Release

Krass M, Rünkorg K, Vasar E, Volke V. Acute administration of GLP-1 receptor agonists induces hypolocomotion but not anxiety in mice.Objective: The aim of this study was to compare the behavioural and hormonal effects of systemic (subcutaneous) treatment with glucaemically equipotent doses of exenatide and liraglutide in mice.Methods: The effects of glucagon-like peptide-1 (GLP-1) receptor agonists were determined on anxiety level in the light–dark compartment test, the motor activity in automated activity cages and finally the forced swimming test was performed.Results: Both exenatide (1–20 µg/kg) and liraglutide (200–1200 µg/kg) decreased the glucose levels up to 30% in freely fed animals. In glucaemically equipotent doses the drugs induced very similar behavioural and hormonal effects: there was no change on anxiety level or immobility time, however, both drugs suppressed motor activity and increased corticosterone levels.Conclusion: We conclude that the two clinically approved GLP-1 receptor agonists induce very similar suppression of motor activity and stimulation of corticosterone release in mice.

Patient-Reported Outcomes following Initiation of Glucagon-Like Peptide-1 Receptor AgonistS (GLP–1RA) in PatientS with Type 2 Diabetes—PROGRESS-DIABETES Study

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1096-P
Author(s):  
RUTH E. BROWN ◽  
ALEXANDER ABITBOL ◽  
HARPREET S. BAJAJ ◽  
HASNAIN KHANDWALA ◽  
RONALD GOLDENBERG ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Patient Reported Outcomes ◽  
Receptor Agonists ◽  
Patient Reported ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

1019-P: Glucagon-Like Peptide-1 Receptor Agonists Predominantly Reduce Body Fat Mass in Patients with Type 2 Diabetes

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1019-P
Author(s):  
YUKI FUJITA ◽  
SODAI KUBOTA ◽  
HITOSHI KUWATA ◽  
DAISUKE YABE ◽  
YOSHIYUKI HAMAMOTO ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Fat ◽  
Fat Mass ◽  
Body Fat Mass ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

974-P: Network Meta-analysis of Once Weekly Glucagon-Like Peptide-1 Receptor Agonists: A Focus on Cardiovascular Safety and Mortality

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 974-P
Author(s):  
OSAMAH ALFAYEZ ◽  
OMAR A. ALMOHAMMED ◽  
OMAR ALKHEZI ◽  
MAJED S. AL YAMI
Keyword(s):  
Meta Analysis ◽  
Cardiovascular Safety ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 agonist therapy in patients with diabetes mellitus and obesity

2020 ◽  
Vol 98 (3) ◽  
pp. 210-217
Author(s):  
A. Yu. Babenko ◽  
Yu. A. Kononova ◽  
M. V. Martjanova ◽  
A. V. Simanenkova ◽  
M. A. Kokina ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Hba1c Level ◽  
High Efficiency ◽  
Receptor Agonists ◽  
Predictors Of Response ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Lipids Metabolism

Due to the high efficiency of glucagon-like peptide-1 (GLP-1) receptor agonists therapy in only a part of patients, the search for predictors of response to the treatment is a relevant problem. Purpose. The purpose is to compare the efficacy of liraglutide and exenatide therapy in obese patients with type 2 diabetes mellitus (T2DM) and to evaluate the predictors of response to glycated hemoglobin (HbA1c), weight and lipids reduction. Material and methods. The study included 47 patients with type 2 diabetes and obesity who received GLP-1 receptor agonists therapy. 26 patients were treated with liraglutide, 21 patients were treated with exenatide. We measured the parameters of carbohydrate and lipid metabolism, the levels of hormones involved in glucose and lipids metabolism and in appetite regulation. Blood pressure was measured. These parameters were evaluated at baseline and after 24 weeks of treatment. Results. Patients receiving exenatide therapy showed a tendency towards more frequent HbA1c level reduction by 1% or more (60% versus 30.4%, p = 0.07). The effects of liraglutide and exenatide on weight and waist circumference were comparable. When assessing the predictors of response to the therapy, a more pronounced decrease in HbA1c level (by 1% or more) was in the patients with a higher initial HbA1c level (8.7 (8.2; 9.7) versus 8.2 (6.9; 8.7)%, p = 0.04), as well as with a higher initial GLP-1 level (0.12 (0.05; 0.17) versus 0.040 (0.01; 0.09) ng/ml.) A more significant decrease in the triglycerides (TG) level was detected in patients with a higher level of glucose-dependent insulinotropic peptide (GIP) before therapy (409 (316.0; 431.4) pg/ml in patients who reduced TG level by 30% or more and 331.5 (324.9; 367.1) pg/ml in patients with a lower decrease in TG level). Among the studied parameters, no predictors of body mass reduction were revealed. Conclusion. Measurement of HbA1c, GLP-1, GIP level may be useful to predict the efficacy of GLP-1 receptor agonists therapy.

Combination of SGLT-2 Inhibitors and GLP-1 Receptor Agonists: Potential Benefits in Surrogate and Hard Endpoints

2018 ◽  
Vol 24 (17) ◽  
pp. 1879-1886 ◽  
Author(s):  
Michael Doumas ◽  
Κonstantinos Imprialos ◽  
Konstantinos Stavropoulos ◽  
Andromachi Reklou ◽  
Alexandros Sachinidis ◽  
...  
Keyword(s):  
Microvascular Complications ◽  
Total Mortality ◽  
Cardiac Risk ◽  
Cvd Risk ◽  
Mortality And Morbidity ◽  
Receptor Agonists ◽  
Risk Patients ◽  
Glucagon Like Peptide 1 ◽  
Glycemic Targets ◽  
Cvd Mortality

Background: The treatment of type 2 diabetes mellitus (T2DM) is complex; only a few patients successfully attain glycemic targets with monotherapy, most requiring drug combination therapy. Methods: The goal of this review was to identify in PubMed the complimentary ways of action leading to clinical benefit (in lowering HbA1c, body weight, renal, and cardiac risk factors and events) of the combination of sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA). Results: SGLT2i, an emerging class of antidiabetic agents with an insulin-independent mechanism of action, are suitable for use in combination with any other class of antidiabetics, including insulin. The use of SGLT2i causes a reduction in Cardiovascular Disease (CVD) morbidity (mainly heart failure-HF) as well as total and CVD mortality. Besides insulin, SGLT2i may also be combined with incretin-based therapies, such as GLP-1 RA. The latter appears to reduce the rate or the progression of both macrovascular (mainly myocardial infarction-MI and stroke) and microvascular complications of DM, having a beneficial effect on all-cause mortality and CVD mortality, as well as CVD events. SGLT2i and GLP-1 RA may have a synergic effect on glucose reduction, weight reduction, renal impairment (both an independent lethal disease and a CVD risk factor) improvement, and cardiac event reduction, because the first reduces HF and related events and the second decreases CVD risk (mainly MI and stroke). Both also reduce total mortality, especially when combined with a statin. Conclusion: The combination of metformin with SGLT2i, GLP-1 RA, and a potent statin, in high CVD risk patients with DM, is expected to substantially reduce CVD mortality and morbidity, improving the quality of life of patients with DM at the same time. Prospective studies are needed to confirm this finding.

Sign in / Sign up

Export Citation Format

Share Document