Abstract 13697: Glucagon-like Peptide-1 Analogue Liraglutide Does Not Improve Microvascular Myocardial Function in Patients With Type 2 Diabetes - a Randomized, Single-blinded Cross Over Trial

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Rebekka Faber ◽  
Mette Zander ◽  
Adam A Pena ◽  
Marie M Michelsen ◽  
Naja D Mygind ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Systolic Blood Pressure ◽  
Coronary Microcirculation ◽  
Short Term ◽  
Short Term Treatment ◽  
Flow Reserve ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Background: Impaired coronary microcirculation is associated with a poor prognosis in patients with type 2 diabetes. In the absence of stenosis of major coronary arteries, coronary flow reserve (CFR) reflects coronary microcirculation. Studies have shown beneficial effects of glucagon-like peptide-1 (GLP-1) on the cardiovascular system. The aim of the study was to explore the short-term effect of GLP-1 treatment on coronary microcirculation estimated by CFR in patients with type 2 diabetes. Methods: Twenty patients with type 2 diabetes and no history of coronary artery disease were treated with the GLP-1 analogue Liraglutide for 10 weeks, in a randomized single-blinded crossover setup. The effect of GLP-1 on coronary microcirculation was evaluated using non-invasive trans-thoracic Doppler-flow echocardiography during dipyridamole induced stress. Data were analysed as two-sample t-test after ensuring no carry over effect. Results: A total of 20 patients (15 male; mean age 57 ± 9; mean BMI 33.1 ± 4.4, mean baseline CFR 2.35 ± 0.45) completed full protocol. There was a small increase in CFR following GLP-1 treatment (change 0.18, CI95% [-0.01; 0.36], p=0.06) but with no difference in effect compared with the no treatment group (0.16, CI95% [-0.08; 0.40], p=0.18). GLP-1 significantly reduced glycated haemoglobin (-10.1 mmol/mol CI95% [-13.9; -6.4], p=<0.001) systolic blood pressure (-10 mmHg CI95% [-17; -3], p=0.01) and weight (-1.9 kg CI95% [-3.6; -0.2], p=0.03). Conclusion: Despite a significant weight-loss, reduction in HbA1c and systolic blood pressure, we did not find a significant improvement in coronary microcirculation after 10 weeks treatment with GLP-1. In our short-term treatment study, we therefore conclude that the GLP-1 analogue Liraglutide does not improve coronary microcirculation in patients with type 2 diabetes. Further long-term studies are needed to explore mechanisms to improve coronary microcirculation in patients with type 2 diabetes.

Subcutaneous glucagon-like peptide-1 (7-36) amide is insulinotropic and can cause hypoglycaemia in fasted healthy subjects

1998 ◽  
Vol 95 (6) ◽  
pp. 719-724 ◽  
Author(s):  
C. Mark B. EDWARDS ◽  
Jeannie F. TODD ◽  
Mohammad A. GHATEI ◽  
Stephen R. BLOOM
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Plasma Glucose ◽  
Healthy Subjects ◽  
Therapeutic Potential ◽  
Double Blind ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

1. Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone released postprandially that stimulates insulin secretion, suppresses glucagon secretion and delays gastric emptying. The insulinotropic action of GLP-1 is more potent under hyperglycaemic conditions. Several published studies have indicated the therapeutic potential of subcutaneous GLP-1 in non-insulin-dependent (Type 2) diabetes mellitus. 2. We investigated whether subcutaneous GLP-1, at a dose shown to improve glycaemic control in early Type 2 diabetes, is insulinotropic at normal fasting glucose concentrations. A double-blind, randomized, crossover study of 10 healthy subjects injected with GLP-1 or saline subcutaneously after a 16 h fast was performed. The effect on cardiovascular parameters was also examined. 3. GLP-1 caused a near 5-fold rise in plasma insulin concentration. After treatment with GLP-1, circulating plasma glucose concentrations fell below the normal range in all subjects. One subject had symptoms of hypoglycaemia after GLP-1. A rise in pulse rate was found which correlated with the fall in plasma glucose concentration. An increase in blood pressure occurred with GLP-1 injection which was seen at the same time as the rise in plasma GLP-1 concentrations. 4. This study indicates that subcutaneous GLP-1 can override the normal homoeostatic mechanism maintaining fasting plasma glucose in man, and is also associated with an increase in blood pressure.

scholarly journals Predictors of effectiveness of glucagon-like peptide-1 receptor agonist therapy in patients with type 2 diabetes and obesity

2019 ◽  
Vol 15 (4) ◽  
pp. 22-30 ◽  
Author(s):  
Ekaterina V. Tikhonenko ◽  
Alina Y. Babenko ◽  
Evgeny V. Shlyakhto
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Weight Loss ◽  
Visceral Obesity ◽  
Metabolic Parameters ◽  
Response Predictors ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Standard Breakfast

Background: Type 2 diabetes mellitus (DM2), which mainly develops from visceral obesity, is a socially significant disease. Reduction of losses from DM2 is a priority in modern medicine development. Glucagon-like peptide-1 receptor agonists (aGLP-1) present one of few groups of antidiabetic drugs that allows to reduce not only glycemia, but also weight in DM2. Taking into account predictors of response to the therapy will allow to reach trearment targets with the highest probability, maintaining a safety of treatment, to optimize recommendations for administration of aGPP-1 as much as possible. Aims: To assess dynamics of metabolic parameters, to identify predictors of reduction in blood glucose, body weight and other metabolic parameters on aGLP-1 therapy in patients with DM2 with body mass index (BMI) 35 kg/m2. Materials and methods: The study involved 33 patients (10 men, 23 women), who had been treated with aGLP-1, the observation period for 24 weeks was planned. 3 patients terminated the participation before the appointed time (1 due to pancreatitis development 2 due to the lack of financial opportunity to purchase the drug). So, 30 patients (10 men, 20 women) were included in the final analysis. Examination consisted of the survey, physical examination with measurement of anthropometric, clinical parameters, filling questionnaires. Data were evaluated at baseline and after 24 weeks of treatment. Results: The study found that patients who achieved weight loss 5% initially had higher BMI (p = 0.028), lower GLP-1 (p = 0.036), had lower level of ghrelin after standard breakfast test (p = 0.022). There was trend (p = 0.071) to greater decrease in BMI in patients with restrictive type of eating behavior compared to patients who had a mixed type. More pronounced decrease in glycemia was noted in patients who had higher fasting plasma glucose level at inclusion (p = 0.001). Dynamics of HbA1c was better in patients with initially higher GLP-1 (p = 0.016) and higher levels of glycemia (p = 0.001). Also, we revealed the statistically significant decrease in triglycerides level, blood pressure by end of the treatment period. Conclusions: Results indicate the different predictors for reduction in weight, glycemia and blood pressure on aGLP-1 therapy. In addition to the metabolic parameters, level of orexigenic and anorexigenic hormones and psycho-social characteristics of patients help to estimate an expected effect of aGLP-1 therapy. When being identifying, the predictors of weight loss and the predictors of carbohydrate metabolism compensation should be studied separately. Identification of response predictors is necessary to optimize indications for this group of drugs administration in DM2.

scholarly journals Impact of glucagon like peptide-1 receptor agonist and sodium glucose cotransporter 2 inhibitors on type 2 diabetes patients with renal impairment

2020 ◽  
Vol 17 (6) ◽  
pp. 147916412097122
Author(s):  
Takeyuki Hiramatsu ◽  
Hiroki Ito ◽  
Shota Okumura ◽  
Yuko Asano ◽  
Daiki Iguchi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Renal Function ◽  
Renal Impairment ◽  
Cardiac Function ◽  
Receptor Agonist ◽  
Sodium Glucose Cotransporter ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Introduction: Diabetes mellitus is a progressive disease with cardiovascular complications. We evaluated the impact of a glucagon like peptide-1 (GLP-1) receptor agonist and sodium glucose cotransporter 2 (SGLT-2) inhibitors dapagliflozin and empagliflozin on renal and cardiac function in type 2 diabetes patients with renal impairment. Materials and methods: A total of 156 patients referred with suboptimal glycemic control were assigned to Group G (GLP-1): n = 72 or Group S (SGLT-2 inhibitor)—dapagliflozin ( n = 52) or empagliflozin ( n = 32). Renal function was assessed every 3 months for 36 months. Cardiovascular parameters were evaluated every 12 months for 36 months. Results: Compared with baseline, HbA1c and systolic blood pressure significantly decreased in both groups ( p < 0.05). The estimated glomerular filtration rate decreased, but without significance. Albuminuria decreased significantly in both groups and then subsequently increased after 30 months in Group S. Diastolic cardiac function, assessed by E/e′ or left atrial volume index, decreased only in Group G at 36 months. Conclusions: The GLP-1 receptor agonist and SGLT-2 inhibitors were effective for glycemic and blood pressure control and for maintaining renal function. The GLP-1 receptor agonist improved diastolic function at 36 months.

scholarly journals Acute effects of the glucagon-like peptide-1 receptor agonist, exenatide, on blood pressure and heart rate responses to intraduodenal glucose infusion in type 2 diabetes

2016 ◽  
Vol 14 (1) ◽  
pp. 59-63 ◽  
Author(s):  
Sony S Thazhath ◽  
Chinmay S Marathe ◽  
Tongzhi Wu ◽  
Jessica Chang ◽  
Joan Khoo ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Heart Rate ◽  
Mean Arterial Blood Pressure ◽  
Receptor Agonist ◽  
Glucose Infusion ◽  
Arterial Blood ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Aim: To evaluate the effects of the glucagon-like peptide-1 receptor agonist, exenatide, on blood pressure and heart rate during an intraduodenal glucose infusion in type 2 diabetes. Methods: Nine subjects with type 2 diabetes were randomised to receive intravenous exenatide or saline control in a crossover design. Glucose (3 kcal min−1) was infused via an intraduodenal manometry catheter for 60 min. Blood pressure, heart rate, and the frequency and amplitude of duodenal pressure waves were measured at regular intervals. Gastrointestinal symptoms were monitored using 100 mm visual analogue scales. Results: During intraduodenal glucose infusion (0–60 min), diastolic ( p(0–60) = 0.03) and mean arterial ( p(0–60) = 0.03) blood pressures and heart rate ( p(0–60) = 0.06; p(0–120) = 0.03)) were higher with exenatide compared to placebo. The increase in the area under the curve for diastolic blood pressure and mean arterial blood pressure was related directly to the suppression of the duodenal motility index with exenatide compared to control ( p = 0.007 and 0.04, respectively). Conclusion: In type 2 diabetes, intravenous exenatide increases mean arterial blood pressure and heart rate during an intraduodenal glucose infusion, supporting the need for further research with exenatide for its potential use in postprandial hypotension.

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