scholarly journals Exploiting the antidiabetic properties of incretins to treat type 2 diabetes mellitus: glucagon-like peptide 1 receptor agonists or insulin for patients with inadequate glycemic control?

2008 ◽  
Vol 158 (6) ◽  
pp. 773-784 ◽  
Author(s):  
Luc F Van Gaal ◽  
Stephen W Gutkin ◽  
Michael A Nauck
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
Cell Function ◽  
Β Cell ◽  
Β Cell Function ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Type 2 diabetes mellitus is associated with progressive decreases in pancreatic β-cell function. Most patients thus require increasingly intensive treatment, including oral combination therapies followed by insulin. Fear of hypoglycemia is a potential barrier to treatment adherence and glycemic control, while weight gain can exacerbate hyperglycemia or insulin resistance. Administration of insulin can roughly mimic physiologic insulin secretion but does not address underlying pathophysiology. Glucagon-like peptide 1 (GLP-1) is an incretin hormone released by the gut in response to meal intake that helps to maintain glucose homeostasis through coordinated effects on islet α- and β-cells, inhibiting glucagon output, and stimulating insulin secretion in a glucose-dependent manner. Biological effects of GLP-1 include slowing gastric emptying and decreasing appetite. Incretin mimetics (GLP-1 receptor agonists with more suitable pharmacokinetic properties versus GLP-1) significantly lower hemoglobin A1c, body weight, and postprandial glucose excursions in humans and significantly improve β-cell function in vivo (animal data). These novel incretin-based therapies offer the potential to reduce body weight or prevent weight gain, although the durability of these effects and their potential long-term benefits need to be studied further. This article reviews recent clinical trials comparing therapy with the incretin mimetic exenatide to insulin in patients with oral treatment failure, identifies factors consistent with the use of each treatment, and delineates areas for future research.

Liraglutide: A Once-Daily Incretin Mimetic for the Treatment of Type 2 Diabetes Mellitus

2009 ◽  
Vol 43 (9) ◽  
pp. 1433-1444 ◽  
Author(s):  
Joshua J Neumiller ◽  
R Keith Campbell
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
Efficacy And Safety ◽  
Β Cell ◽  
Once Daily ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Objective: To review the pharmacology, pharmacokinetics, efficacy, and safety of liraglutide, a glucagon-like peptide 1 (GLP-1) analog for the treatment of type 2 diabetes mellitus. Data Sources: A MEDLINE search (1966–May 2009) was conducted for English-language articles using the terms glucagon-like peptide 1, incretin mimetic, NN2211, and liraglutide. Abstracts presented at the American Diabetes Association and European Association for the Study of Diabetes annual meetings in 2006, 2007, and 2008 were also searched for relevant data. Study Selection and Data Extraction: Articles pertinent to the pharmacology, pharmacokinetics, efficacy, and safety of liraglutide were reviewed. Data Synthesis: Liraglutide is a GLP-1 analog with pharmacokinetic properties suitable for once-daily administration. Clinical trial data from large, controlled studies demonstrate the effectiveness of liraglutide in terms of hemoglobin A1c (A1C) reduction, reductions in body weight, and the drug's low risk for hypoglycemic events when used as monotherapy. Data also support benefits of liraglutide therapy on β-cell responsiveness to glucose, with animal and in vitro data indicating potential benefits in β-cell mass and neogenesis with liraglutide treatment. Liraglutide has been studied as monotherapy and in combination with metformin, glimepiride, and rosiglitazone for the treatment of type 2 diabetes. Additionally, comparative data with insulin glargine and exenatide therapy are available from Phase 3 trials providing practitioners valuable clinical data on which to base clinical decision making. Overall, liraglutide is well tolerated with dose-dependent nausea, vomiting, and diarrhea being the most commonly reported adverse events in clinical trials. Conclusions: Once-daily administration may provide a therapeutic advantage for liraglutide over twice-daily exenatide, with similar improvements in A1C and body weight observed when liraglutide was compared with exenatide. The glucose-dependent mechanism of insulin release with GLP-1 agonist therapy holds potential clinical significance in the management of postprandial hyperglycemic excursions, with minimal risk of hypoglycemia.

scholarly journals The experience with the clinical application of liralgutide (victosa), the first analog of human glucagon-like peptide-1 in the patients with type 2 diabetes mellitus - expanding the range of possibilities

2012 ◽  
Vol 58 (3) ◽  
pp. 51-55
Author(s):  
E N Ostroukhova ◽  
O K Khmel'nitskiĭ ◽  
E I Krasil'nikova ◽  
K S Davidenko
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
Adverse Reactions ◽  
Brand Name ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting

This paper reports the results of the treatment of 71 patients presenting with type 2 diabetes mellitus using liraglutide, a long-acting analog of glucagon-like peptide-1 (GLP-1) marketed under the brand name Victoza. Practically all the patients experienced either improvement or normalization of the parameters of carbohydrate metabolism in conjunction with a reduction of their body weight and arterial pressure. There were no severe hypoglycemic episodes and other adverse reactions to the therapy. It is recommended that Victoza should be more widely used for the treatment of the patients with type 2 diabetes mellitus.

scholarly journals The Clinical Efficacy and Safety of Glucagon-Like Peptide-1 (GLP-1) Agonists in Adults with Type 2 Diabetes Mellitus

2011 ◽  
Vol 4 ◽  
pp. CMED.S4086 ◽  
Author(s):  
Kira R. Brice ◽  
Maria K. Tzefos
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cell Function ◽  
Efficacy And Safety ◽  
Medline Search ◽  
Study Selection ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Objective To review the efficacy and safety of glucagon-like peptide-1 (GLP-1) agonists to determine their role in type 2 diabetes mellitus (T2DM). Data Sources A Medline search was conducted using the keywords exenatide, liraglutide, glucagon-like peptide-1, type 2 diabetes mellitus, hyperglycemia, pharmacokinetics, pharmacology and safety. Study Selection All identified articles written in English were evaluated with priority given to controlled, randomized trials including human data. References of identified published trials were reviewed for additional trials to be included in the review. Data Synthesis Exenatide and liraglutide are GLP-1 agonists approved for the treatment of T2DM. Several randomized, active and placebo controlled trials examining the efficacy and safety of exenatide and liraglutide both as monotherapy and in combination therapy have been conducted. Both agents have demonstrated improved glycemic control in addition to weight loss and increased beta-cell function. The most common adverse effects are gastrointestinal in nature and appear to be transient. Conclusion It appears exenatide and liraglutide are safe and effective in the treatment of T2DM and may exhibit effects that make them preferred over other anti-diabetic medications.

scholarly journals Diabetic Retinopathy in Newly Diagnosed Subjects With Type 2 Diabetes Mellitus: Contribution of β-Cell Function

2016 ◽  
Vol 101 (2) ◽  
pp. 572-580 ◽  
Author(s):  
Sharmistha Roy Chowdhury ◽  
Rebecca L. Thomas ◽  
Gareth J. Dunseath ◽  
Rajesh Peter ◽  
D. Aled Rees ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Cell Function ◽  
Newly Diagnosed ◽  
Β Cell ◽  
Β Cell Function

Impact of insulin glargine and lixisenatide on β-cell function in patients with type 2 diabetes mellitus: A randomized open-label study

2017 ◽  
Vol 19 (11) ◽  
pp. 1625-1629 ◽  
Author(s):  
Juris J. Meier ◽  
Nina Schenker ◽  
Melanie Kahle ◽  
Freimut Schliess ◽  
Christoph Kapitza ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cell Function ◽  
Β Cell ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Β Cell Function

scholarly journals XOMA 052, an Anti-IL-1β Monoclonal Antibody, Improves Glucose Control and β-Cell Function in the Diet-Induced Obesity Mouse Model

2010 ◽  
Vol 31 (2) ◽  
pp. 261-261
Author(s):  
Alexander M. Owyang ◽  
Kathrin Maedler ◽  
Lisa Gross ◽  
Johnny Yin ◽  
Lin Esposito ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Monoclonal Antibody ◽  
Type 2 Diabetes Mellitus ◽  
Cell Function ◽  
Cell Mass ◽  
Β Cell ◽  
Diet Induced Obesity ◽  
Β Cell Function

ABSTRACT Recent evidence suggests that IL-1β-mediated glucotoxicity plays a critical role in type 2 diabetes mellitus. Although previous work has shown that inhibiting IL-1β can lead to improvements in glucose control and β-cell function, we hypothesized that more efficient targeting of IL-1β with a novel monoclonal antibody, XOMA 052, would reveal an effect on additional parameters affecting metabolic disease. In the diet-induced obesity model, XOMA 052 was administered to mice fed either normal or high-fat diet (HFD) for up to 19 wk. XOMA 052 was administered as a prophylactic treatment or as a therapy. Mice were analyzed for glucose tolerance, insulin tolerance, insulin secretion, and lipid profile. In addition, the pancreata were analyzed for β-cell apoptosis, proliferation, and β-cell mass. Mice on HFD exhibited elevated glucose and glycated hemoglobin levels, impaired glucose tolerance and insulin secretion, and elevated lipid profile, which were prevented by XOMA 052. XOMA 052 also reduced β-cell apoptosis and increased β-cell proliferation. XOMA 052 maintained the HFDinduced compensatory increase in β-cell mass, while also preventing the loss in β-cell mass seen with extended HFD feeding. Analysis of fasting insulin and glucose levels suggests that XOMA 052 prevented HFD-induced insulin resistance. These studies provide new evidence that targeting IL-1β in vivo could improve insulin sensitivity and lead to β-cell sparing. This is in addition to previously reported benefits on glycemic control. Taken together, the data presented suggest that XOMA 052 could be effective for treating many aspects of type 2 diabetes mellitus.

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