Subcutaneous glucagon-like peptide-1 improves postprandial glycaemic control over a 3-week period in patients with early Type 2 diabetes

1998 ◽  
Vol 95 (3) ◽  
pp. 325-329 ◽  
Author(s):  
Jeannie F. TODD ◽  
C. Mark B. EDWARDS ◽  
Mohammad A. GHATEI ◽  
Hugh M. MATHER ◽  
Stephen R. BLOOM
Keyword(s):  
Type 2 Diabetes ◽  
Glycaemic Control ◽  
Plasma Glucose ◽  
Test Meal ◽  
Insulin Response ◽  
Standard Test ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
First Phase Insulin Response

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.

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 Lixisenatide – A New Glucagon-like Peptide 1 Receptor Agonist in the Treatment of Type 2 Diabetes

2010 ◽  
Vol 9 (2) ◽  
pp. 76 ◽  
Author(s):  
Josep Vidal ◽  
Keyword(s):  
Type 2 Diabetes ◽  
Glycaemic Control ◽  
Basal Insulin ◽  
Glycated Haemoglobin ◽  
Insulin Analogues ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting

Optimal glycaemic control is essential to managing risks in patients with type 2 diabetes. However, glycaemic control remains poor among type 2 diabetes patients, particularly the control of post-prandial glucose (PPG). Almost half of patients treated with basal insulin and oral anti-diabetic drugs (OADs) do not achieve their glycated haemoglobin (HbA1c) goals, despite achieving fasting plasma glucose (FPG) control. Glycaemic control targets have emphasised FPG targets, but PPG contributes significantly to overall glycaemic control in type 2 diabetes. Glucagon-like peptide 1 (GLP-1) receptor agonists have shown substantial efficacy in improving overall glycaemic control but have differing effects on PPG, which is a result of their different mechanisms of action. Lixisenatide is unique among existing GLP-1 receptor agonists in that it is short acting but given as a once daily dose, and exerts its main effects during the prandial period. It has demonstrated efficacy in an extensive clinical trial programme. In particular, it has shown a beneficial effect on PPG compared with existing GLP-1 receptor agonists, probably a result of its effect on slowing gastric emptying. This has provided a strong rationale for its use as add-on therapy to long-acting basal insulin analogues, in cases where the latter is not providing adequate glycaemic control. The additive effects on glycaemic control may lead to a new treatment approach to manage blood glucose and prevent long-term complications in patients with type 2 diabetes.

Oral semaglutide in the management of type 2 DM: Clinical status and comparative analysis

2021 ◽  
Vol 22 ◽  
Author(s):  
Ilora Bandyopadhyay ◽  
Sunny Dave ◽  
Amita Rai ◽  
Madhavan Nampoothiri ◽  
Mallikarjuna Rao Chamallamudi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Comparative Analysis ◽  
Glycaemic Control ◽  
Receptor Agonist ◽  
Review Article ◽  
Second Line ◽  
Type 2 Dm ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Background: In the incretin system, Glucagon-like peptide-1 (GLP-1) is a hormone that inhibits the release of glucagon and regulates glucose-dependent insulin secretion. In type 2 diabetes, correcting the impaired incretin system using GLP-1 agonist is a well-defined therapeutic strategy. Objectives: This review article aims to discuss the mechanism of action, key regulatory events, clinical trials for glycaemic control and comparative analysis of semaglutide with the second-line antidiabetic drugs. Description: Semaglutide is a glucagon-like peptide 1 (GLP 1) receptor agonist with enhanced glycaemic control in diabetes patients. In 2019, USFDA approved the first oral GLP-1 receptor agonist, semaglutide to be administered as a once-daily tablet. Further, recent studies highlight the ability of semaglutide to improve the glycaemic control in obese patients with a reduction in body weight. Still, in clinical practice, in type 2 DM treatment paradigm the impact of oral semaglutide remains unidentified. This review article discusses the mechanism of action, pharmacodynamics, key regulatory events, and clinical trials regarding glycaemic control. Conclusion: The review highlights the comparative analysis of semaglutide with the existing second-line drugs for the management of type 2 diabetes mellitus by stressing on its benefits and adverse events.

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