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.

scholarly journals Effect of probiotics and incretine mimeticss on the levels of glucagon-like peptide-1 in blood serum of patients with type 2 diabetes mellitus

2021 ◽  
Vol 17 (8) ◽  
pp. 604-612
Author(s):  
K.A. Shyshkan-Shyshova ◽  
O.V. Zinych ◽  
N.M. Kushnareva ◽  
A.V. Кovalchuk ◽  
O.V. Prybyla
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Body Composition ◽  
Intestinal Microbiota ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Group 2

Background. Type 2 diabetes mellitus is characterized by a violation of the incretin effect, in particular a decrease in the secretion of glucagon-like peptide-1 (GLP-1) by intestinal endothelial cells. In recent decades, the intestinal microbiota has been shown to play a key role in the regulation of various metabolic pathways, immune system activity, and intestinal permeability. It has been shown that the composition of bacterial genera in the intestine can unfluence the effectiveness of antidiabetic drugs (eg metformin and GLP-1 receptor agonists), which may be reduced in dysbiosis. Therefore, it is of interest to study the mechanisms that mediate the effect of microbiota on the incretin secretion. The purpose was to establish the relationship between the effects of probiotic therapy, incretin therapy and the level of endogenous GLP-1 in the serum of patients with type 2 diabetes mellitus, taking into account anthropometry and body composition. Materials and methods. We examined 23 patients with type 2 diabetes mellitus (11 women and 12 men), their average age was 56.4 ± 10.5 years (M ± SD). At the beginning of the study, the mean HbA1c level was 7.7 ± 1.5 %; all patients took metformin at an average dose of 1,500 mg/day. Patients were randomized into 2 groups: group 1 (n = 11) received a probiotic, group 2 (n = 12) — a long-acting GLP-1 receptor agonist. The concentration of GLP-1 in the blood serum was determined by the enzyme-linked immunosorbent assay, anthropometry parameters and body composition were assessed using the Tanita analyzer. Results. In the group of patients who took the probiotic, a significant increase in GLP-1 was observed, but less pronounced compared to an increase in GLP-1 level in the group of patients who took GLP-1 receptor agonists. In group 2, on the background of taking GLP-1 receptor agonists, a significant decrease in body weight, total and abdominal fat content, and a decrease in dehydration were revealed. Conclusions. An increase in the concentration of endogenous GLP-1 against the background of probiotic therapy indicates a possible positive effect of normalization of the intestinal microbiota on the secretion of endogenous incretins. The results obtained suggest that the use of a combination of probiotic and GLP-1 receptor agonists may have an additive effect on the hormonal and metabolic profile in patients with type 2 diabetes mellitus.

scholarly journals Effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events in patients with Type 2 diabetes mellitus with or without established cardiovascular disease: a meta-analysis of randomized controlled trials

2020 ◽  
Vol 41 (35) ◽  
pp. 3346-3358 ◽  
Author(s):  
Fabio Marsico ◽  
Stefania Paolillo ◽  
Paola Gargiulo ◽  
Dario Bruzzese ◽  
Simona Dell’Aversana ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cardiovascular Events ◽  
Meta Analysis ◽  
Receptor Agonists ◽  
Type 2 Dm ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Aims  Glucose-lowering, glucagon-like peptide-1 (GLP-1) receptor agonists reduce incidence of major cardiovascular (CV) events in patients with Type 2 diabetes mellitus (DM). However, randomized clinical trials reported inconsistent effects on myocardial infarction (MI) and stroke, and limited data in DM patients without established CV disease (CVD). Very recently, new relevant evidence was available from additional CV outcome trials (CVOTs) that also included large subgroups of patients with DM without established CVD. Thus, the aim of this meta-analysis was to investigate the effects of GLP-1 receptor agonists on major CV events and safety in DM patients with and without established CVD. Methods and results  In this trial-level meta-analysis, we analysed data from randomized placebo-controlled CVOTs assessing efficacy and safety of GLP-1 receptor agonists in adult patients with Type 2 DM. We searched PubMed, Embase, Cochrane, ISI Web of Science, SCOPUS, and clinicaltrial.gov databases for eligible trials. Of 360 articles identified and screened for eligibility, seven CVOTs were included, with an overall of 56 004 patients included. The difference in efficacy with respect to the major adverse cardiovascular events (MACE) primary endpoint (including CV mortality, non-fatal MI, and non-fatal stroke) between patients with established CVD and patients with CV risk factors only was not significant [pooled interaction effect, expressed as ratio of hazard ratio (HR) 1.06, 95% confidence interval (CI) 0.85–1.34]. In the analysis of the whole population of DM patients, GLP-1 receptor agonists showed a significant 12% reduction in the hazard of the three-point MACE composite endpoint (HR 0.88, 95% CI 0.80–0.96) and a significant reduction in the risk of CV mortality (HR 0.88, 95% CI 0.79–0.98), all-cause mortality (HR 0.89, 95% CI 0.81–0.97), fatal and non-fatal stroke (HR 0.84, 95% CI 0.76–0.94), and heart failure (HF) hospitalization (HR 0.92, 95% CI 0.86–0.97). No significant effect was observed for fatal and non-fatal MI (HR 0.91, 95% CI 0.82–1.02), although in a sensitivity analysis, based on a less conservative statistical approach, the pooled HR become statistically significant (HR 0.91, 95% CI 0.83–1.00; P = 0.039). No excess of hypoglycaemia, pancreatitis, and pancreatic cancer was observed between GLP-1 receptor agonists and placebo. Conclusion  Glucagon-like peptide-1 receptor agonists significantly reduce MACE, CV and total mortality stroke, and hospitalization for HF, with a trend for reduction of MI, in patients with Type 2 DM with and without established CVD.

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