Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes

1.Glucagon-like peptide-1 (7-36) amide (GLP-1) is released into the circulation after meals and is the most potent physiological insulinotropic hormone in man. GLP-1 has the advantages over other therapeutic agents for Type 2 diabetes of also suppressing glucagon secretion and delaying gastric emptying. One of the initial abnormalities of Type 2 diabetes is the loss of the first-phase insulin response, leading to postprandial hyperglycaemia. 2.To investigate the therapeutic potential of GLP-1 in Type 2 diabetes, six patients were entered into a 6-week, double-blind crossover trial during which each received 3 weeks treatment with subcutaneous GLP-1 or saline, self-administered three times a day immediately before meals. A standard test meal was given at the beginning and end of each treatment period. 3.GLP-1 reduced plasma glucose area under the curve (AUC) after the standard test meal by 58% (AUC, 0–240 ;min: GLP-1 start of treatment, 196±141 ;mmol·min-1·l-1; saline start of treatment, 469±124 ;mmol·min-1·l-1; F = 16.4, P< 0.05). The plasma insulin excursions were significantly higher with GLP-1 compared with saline over the initial postprandial 30 ;min, the time period during which the GLP-1 concentration was considerably elevated. The plasma glucagon levels were significantly lower over the 240-min postprandial period with GLP-1 treatment. The beneficial effects of GLP-1 on plasma glucose, insulin and glucagon concentrations were fully maintained for the 3-week treatment period. 4.We have demonstrated a significant improvement in postprandial glycaemic control with subcutaneous GLP-1 treatment. GLP-1 improves glycaemic control partially by restoring the first-phase insulin response and suppressing glucagon and is a potential treatment for Type 2 diabetes.

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Intravenous glucagon-like peptide 1 normalizes blood glucose after major surgery in patients with type 2 diabetes

Critical Care Medicine ◽

10.1097/01.ccm.0000114811.60629.b5 ◽

2004 ◽

Vol 32 (3) ◽

pp. 848-851 ◽

Cited By ~ 60

Author(s):

Juris J. Meier ◽

Dirk Weyhe ◽

Mark Michaely ◽

Metin Senkal ◽

Volker Zumtobel ◽

...

Keyword(s):

Type 2 Diabetes ◽

Blood Glucose ◽

Major Surgery ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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Lixisenatide: A New Daily GLP-1 Agonist for Type 2 Diabetes Management

Annals of Pharmacotherapy ◽

10.1177/1060028017689878 ◽

2017 ◽

Vol 51 (5) ◽

pp. 401-409 ◽

Cited By ~ 8

Author(s):

Delilah McCarty ◽

Megan Coleman ◽

Cassie L. Boland

Keyword(s):

Type 2 Diabetes ◽

Blood Glucose ◽

Gastric Emptying ◽

Diabetes Management ◽

Human Subjects ◽

Data Extraction ◽

Postprandial Blood Glucose ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of the glucagon-like peptide-1 receptor agonist (GLP-1RA), lixisenatide, in the treatment of type 2 diabetes mellitus. Data Sources: A PubMed (1966-2016) search was conducted using the following keywords: lixisenatide, AVE0010, glucagon-like peptide-1 agonist, and type 2 diabetes. References were reviewed to identify additional sources. Study Selection and Data Extraction: Articles written in English were included if they evaluated the pharmacology, pharmacokinetics, efficacy, or safety of lixisenatide in human subjects. Data Synthesis: Lixisenatide lowers blood glucose through a glucose-dependent increase in insulin release from pancreatic β-cells and a decreased release of glucagon from pancreatic α-cells. Additionally, lixisenatide delays gastric emptying and increases satiety. Lixisenatide has been studied head to head against exenatide and insulin glulisine. It has also been studied as monotherapy and in combination with metformin, sulfonylureas, pioglitazone, and insulin glargine. In the GetGoal clinical trial series, lixisenatide resulted in a hemoglobin A1C reduction of 0.6% to 1% and a reduction in body weight of 0.2 to 2.96 kg. The adverse effect profile of lixisenatide was consistent with that of other GLP-1RAs, with nausea, vomiting, and diarrhea most commonly reported. Conclusion: Lixisenatide provides an additional GLP-1RA option, which may have more postprandial blood glucose-lowering effects than the other agents in the class because of its shorter half-life and effects on delaying gastric emptying.

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Glucagon-like peptide-1 analog liraglutide in combination with sulfonylurea safely improves blood glucose measures vs sulfonylurea monotherapy in Japanese patients with type 2 diabetes: Results of a 52-week, randomized, multicenter trial

Journal of Diabetes Investigation ◽

10.1111/j.2040-1124.2011.00103.x ◽

2011 ◽

Vol 2 (4) ◽

pp. 280-286 ◽

Cited By ~ 21

Author(s):

Yutaka Seino ◽

Mads Frederik Rasmussen ◽

Tomoyuki Nishida ◽

Kohei Kaku

Keyword(s):

Type 2 Diabetes ◽

Blood Glucose ◽

Japanese Patients ◽

Multicenter Trial ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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L-Glutamine and Whole Protein Restore First-Phase Insulin Response and Increase Glucagon-Like Peptide-1 in Type 2 Diabetes Patients

Nutrients ◽

10.3390/nu7042101 ◽

2015 ◽

Vol 7 (4) ◽

pp. 2101-2108 ◽

Cited By ~ 8

Author(s):

Dorit Samocha-Bonet ◽

Don Chisholm ◽

Jens Holst ◽

Jerry Greenfield

Keyword(s):

Type 2 Diabetes ◽

Insulin Response ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

First Phase Insulin Response ◽

Diabetes Patients

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Comparing the Efficacy and Safety of Glucagon-Like Peptide 1 Receptor Agonists with Sodium-Glucose Cotransporter 2 Inhibitors for Obese Type 2 Diabetes Patients Uncontrolled on Metformin: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

International Journal of Endocrinology ◽

10.1155/2020/1626484 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Lu Ding ◽

Bang Sun ◽

Xinhua Xiao ◽

Tatsuya Kin

Keyword(s):

Type 2 Diabetes ◽

Clinical Trials ◽

Blood Glucose ◽

Meta Analysis ◽

Controlled Trials ◽

Sodium Glucose Cotransporter ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Introduction. To conduct the first meta-analysis of randomized controlled trials (RCTs) comparing glucagon-like peptide 1 receptor agonists (GLP-1RAs) with sodium-glucose cotransporter 2 inhibitors (SGLT-2is) for obese type 2 diabetes (T2D) patients uncontrolled on metformin. Methods. We searched Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Ovid, and Web of Science from inception to May 14, 2020, without language restrictions for eligible RCTs. The primary outcome is the mean change from baseline in glycated haemoglobin (HbA1c). Results. Totally, 3 RCTs enrolled 2066 patients were identified. Compared with SGLT-2is, treatment with GLP-1RAs achieved significant reduced HbA1c by 0.40% (95% CI: −0.54, −0.25; p < 0.00001 ), fasting blood glucose (FBG) by 0.17 mmol/L (95% CI: −0.31, −0.04; p = 0.01 ), and postprandial blood glucose (PBG) by 0.32 mmol/L (95% CI: −0.49, −0.14; p = 0.0003 ) for obese T2D patients uncontrolled on metformin. The significant benefit of weight loss was seen in semaglutide (MD: −0.75; 95% CI: −1.18, −0.31; p < 0.0007 ). No significant difference was detected between GLP-1RAs and SGLT-2is in overall adverse events (RR: 1.03; 95% CI: 0.98, 1.09; p = 0.76 ), but gastrointestinal events showed higher occurrence in GLP-1RAs groups compared with SGLT-2is (RR: 1.62; 95% CI: 1.37, 1.93; p < 0.00001 ). Subgroup analyses revealed that follow-up time did not statistically influence glycemic control. Conclusion. GLP-1RAs are superior to SGLT-2is for obese T2D patients uncontrolled on metformin in glycemic control without an increase in adverse events except for a higher occurrence in gastrointestinal events. Future large longer-term follow-up clinical trials are needed to provide more evidence about the sustainable effects and safety of GLP-1RAs compared with SGLT-2is.

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Diabetes and obesity. The role of agonists glucagon-like peptide-1 of in the treatment of type 2 diabetes

Diabetes Mellitus ◽

10.14341/dm9623 ◽

2018 ◽

Vol 21 (4) ◽

pp. 293-300 ◽

Cited By ~ 1

Author(s):

Nina A. Petunina ◽

Milena Е. Telnova

Keyword(s):

Type 2 Diabetes ◽

Insulin Response ◽

Diabetic Patients ◽

Incretin Effect ◽

Receptor Agonists ◽

Number Of Patients ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Diabetes And Obesity

Significant number of patients with type 2 diabetes mellitus are obese. It is known that even glucose intolerance, as well as diabetes, can lead to vascular complications. At the same time, weight loss can reduce the risk of type 2 diabetes in obese and pre-diabetic patients. According to available data, a significant decrease in the incretin effect is observed in patients with type 2 diabetes and obese individuals. Thus, a decrease in the incretin effect leads to a violation of the insulin response to the intake of carbohydrates, and, consequently, an increase in the level of glucose in the blood. It was also found that the decrease in the incretin effect in patients with type 2 diabetes can be associated with a lower secretion of glucagon-like peptide-1. The interest is represented by groups of antidiabetic drugs capable of regulating glycemia by affecting the secretion of insulin and glucagon, depending on its level. Such drugs include glucagon-like peptide-1 receptor agonists. The article shows the advantage of prolonged action in patients with type 2 diabetes and obesity of the glucagon-like peptide 1 receptor agonists (albiglutide, dulaglutide, exenatide with slow release) dosing 1 time a week.

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