Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently, the European Medicines Agency (EMEA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending to grant a marketing authorization for liraglutide for the treatment of type 2 diabetes mellitus. Liraglutide is the first human glucagon-like peptide-1 (GLP-1) analog, based on the structure of native GLP-1, with pharmacokinetic properties suitable for once-daily dosing. In the phase III Liraglutide Effect and Action in Diabetes (LEAD) program, liraglutide has been shown to lower glycated hemoglobin to the same extent or more than other antidiabetic drugs including insulin. Liraglutide determines favorable changes in the global cardiovascular risk profile because its use is associated with weight loss, blood pressure reduction, as well as improvements of several cardiovascular risk biomarkers. Liraglutide is generally well tolerated, the most frequently reported adverse effect is transient nausea, and it does not seems to have significant interactions with medications commonly used for cardiovascular prevention. This article reviews, for the practicing cardiologist, the results of the LEAD program and explores liraglutide potentials for cardiovascular prevention in type 2 diabetes mellitus.
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PMID:[Drug therapy of type 2 diabetes and cardiovascular prevention: potentials for liraglutide]. 1976 Nov 1

Type 2 diabetes is a progressive disease characterized by insulin resistance and impaired beta-cell function. Treatments that prevent further beta-cell decline are therefore essential for the management of type 2 diabetes. Glucagon-like peptide-1 (GLP-1) is an incretin hormone that is known to stimulate glucose-dependent insulin secretion. Furthermore, GLP-1 appears to have multiple positive effects on beta cells. However, GLP-1 is rapidly degraded by dipeptidyl peptidase-4 (DPP-4), which limits the clinical relevance of GLP-1 for the treatment of type 2 diabetes. Two main classes of GLP-1-based therapies have now been developed: DPP-4 inhibitors and GLP-1 receptor agonists. Liraglutide and exenatide are examples of GLP-1 receptor agonists that have been developed to mimic the insulinotropic characteristics of endogenous GLP-1. Both have demonstrated improved beta-cell function in patients with type 2 diabetes, as assessed by homoeostasis model assessment-B analysis and proinsulin : insulin ratio. Additionally, liraglutide and exenatide are able to enhance first- and second-phase insulin secretion and are able to restore beta-cell sensitivity to glucose. Preclinical studies have shown that both liraglutide and exenatide treatment can increase beta-cell mass, stimulate beta-cell proliferation, increase beta-cell neogenesis and inhibit beta-cell apoptosis. Clinical studies are needed to confirm these findings in humans. Replication of these data in humans could have important clinical implications for the treatment of type 2 diabetes.
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PMID:The effects of glucagon-like peptide-1 on the beta cell. 1987 57

Liraglutide is a new glucagon-like peptide-1 (GLP-1) receptor agonist and a true GLP-1 analogue. After successful phase 2 studies, liraglutide was assessed in a series of phase 3 trials [(Liraglutide Effect and Action in Diabetes (LEAD)] designed to demonstrate efficacy and safety across the continuum of type 2 diabetes antihyperglycaemic care, both as monotherapy and in combination with commonly used oral antidiabetic drugs (OADs). The LEAD programme also compared liraglutide with other OADs. As a monotherapy, liraglutide demonstrated significant improvements in glycaemic control in comparison with glimepiride. When combined with one or two OADs, reductions in haemoglobin A1c, fasting plasma glucose and postprandial glucose were generally greater with liraglutide than with comparators. Throughout the trials, liraglutide was associated with weight reduction; in most instances, the reduction from baseline was significantly greater than that seen with comparators. Improvements in assessments of beta-cell function were consistently shown with liraglutide treatment across all trials. Furthermore, reductions in systolic blood pressure were reported. Liraglutide was associated with a low risk of hypoglycaemia and was generally well tolerated. The majority of adverse effects were gastrointestinal, the most frequent of which was nausea.
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PMID:The safety and efficacy of liraglutide with or without oral antidiabetic drug therapy in type 2 diabetes: an overview of the LEAD 1-5 studies. 1987 59

Despite the continued development of new pharmacologic agents, and the use of several existing drug therapies, almost two thirds of patients with type 2 diabetes mellitus do not reach the American Diabetes Association-targeted hemoglobin A(1c) level of less than 7.0%. Therefore, maintaining adequate metabolic control remains a primary concern for many clinicians and patients. It is now well recognized that in addition to defective secretion and action of insulin, other hormones also potentially play a role in the development and progression of type 2 diabetes. Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone from the incretin family, which stimulates insulin secretion and plays an important role in regulating the enteroinsular axis. Incretin-based therapies are the newest class of glucose-lowering drugs for the treatment of type 2 diabetes and may help address some of the unmet needs in this therapeutic area. Liraglutide is a once-daily GLP-1 analog that has been recently approved by the European Union regulatory agency and is in late-stage review by the United States Food and Drug Administration for the treatment of type 2 diabetes. The pharmacokinetic and pharmacodynamic properties of liraglutide and mechanisms behind its protracted action, which in turn enables enhanced glycemic control, are reviewed.
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PMID:Pharmacokinetics and pharmacodynamics of liraglutide, a long-acting, potent glucagon-like peptide-1 analog. 1994 15

Liraglutide, a new glucagon-like peptide-1 (GLP-1)-receptor agonist with 97% homology to human GLP-1, can be administered once/day independent of meals in patients with type 2 diabetes mellitus. Clinical trials have demonstrated its efficacy in controlling hyperglycemia, helping patients achieve hemoglobin A(1c) level goals; in facilitating weight loss, and in improving indexes of beta-cell function when used alone or in combination with metformin, glimepiride, or rosiglitazone. These studies also suggest that liraglutide may be associated with modest improvements in systolic blood pressure. Data from a comparative trial of liraglutide and insulin glargine have suggested that liraglutide provides greater glycemic control with less weight gain, and another study demonstrated that liraglutide provides greater improvements in glycemic control with less hypoglycemia than exenatide and with comparable weight loss. Although liraglutide is well tolerated and is associated with low rates of hypoglycemia, transient and mild nausea can occur when therapy is initiated. However, rates of hypoglycemia appear to be lower and nausea appears to be less persistent with liraglutide than with exenatide. Even though data on the long-term use of liraglutide are still needed, this drug may provide a useful treatment option in patients poorly controlled with dietary modification and exercise and in those whose diabetes is inadequately controlled by oral antidiabetic agents.
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PMID:Clinical studies of liraglutide, a novel, once-daily human glucagon-like peptide-1 analog for improved management of type 2 diabetes mellitus. 1994 16

Type 2 diabetes has been identified as a risk factor for patients with Alzheimer's disease. Insulin signalling is often impaired in Alzheimer's disease, contributing to the neurodegenerative process. One potential strategy to help prevent this is the normalisation of insulin signalling in the brain. Therefore, the present study was designed to test the effects of novel enzyme-resistant analogues of the insulin-releasing incretin hormone, glucagon-like peptide 1 (GLP-1). The effects of Liraglutide (Victoza) and other novel GLP-1 analogues were tested on synaptic plasticity (LTP) in area CA1 of the hippocampus. At a dose of 15nmol in 5microl i.c.v., Liraglutide (P<0.005), Asp(7)GLP-1 (P<0.001), N-glyc-GLP-1 (P<0.01), and Pro(9)GLP-1 (P<0.001). In contrast, the GLP-1 receptor antagonist exendin(9-39)amide impaired LTP (P<0.001). Co-injection of exendin(9-39) and Liraglutide showed no effect on LTP. These results clearly demonstrate that Liraglutide and other GLP-1 analogues elicit effects on neurotransmission in the brain. Furthermore, GLP-1 peptides are not only effective in modulating insulin-release and achieving glycaemic control in type 2 diabetes, but are also effective in modulating synaptic plasticity. These findings are consistent with our previous observations that the novel analogue (Val(8))GLP-1 enhances LTP and reverses the impairments of LTP induced by beta-amyoid fragments. Therefore, the drug effects seen here could potentially ameliorate the impairments in neuronal communication and cognitive processes observed in Alzheimer's disease.
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PMID:Glucagon-like peptide-1 analogues enhance synaptic plasticity in the brain: a link between diabetes and Alzheimer's disease. 2003 39

The once-daily human glucagon-like peptide-1 (GLP-1) analog, liraglutide, was recently shown to provide improved glycemic control in subjects with type 2 diabetes (T2D) compared with exenatide. The aim of this work is to estimate the population pharmacokinetics of liraglutide and make a comparison to the pharmacokinetic profile of exenatide. Pharmacokinetic data from 5 published studies of subcutaneous and intravenous administration of liraglutide to healthy volunteers (HV) and subjects with T2D were used to develop a population pharmacokinetic model in NONMEM. Exenatide data came from a published study in T2D. Liraglutide pharmacokinetics were adequately described using a 1-compartment model with sequential zero- and first-order absorption. The pharmacokinetic profile of once-daily liraglutide showed considerably smaller peak-to-trough fluctuations compared with twice-daily exenatide. A small difference in the estimates of absorption parameters was found between HV and subjects with T2D but was not clinically relevant. It was concluded that pharmacokinetic profiles estimated by modeling showed that liraglutide has pharmacokinetic properties consistent with once-daily dosing in humans and provides better pharmacokinetic coverage in comparison with twice-daily exenatide. Furthermore, no clinically relevant differences were found in liraglutide pharmacokinetics between HV and subjects with T2D.
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PMID:Population pharmacokinetics of liraglutide, a once-daily human glucagon-like peptide-1 analog, in healthy volunteers and subjects with type 2 diabetes, and comparison to twice-daily exenatide. 2013 7

Liraglutide is a glucagon-like peptide-1 (GLP-1) analog developed for type 2 diabetes. Long-term liraglutide exposure in rodents was associated with thyroid C-cell hyperplasia and tumors. Here, we report data supporting a GLP-1 receptor-mediated mechanism for these changes in rodents. The GLP-1 receptor was localized to rodent C-cells. GLP-1 receptor agonists stimulated calcitonin release, up-regulation of calcitonin gene expression, and subsequently C-cell hyperplasia in rats and, to a lesser extent, in mice. In contrast, humans and/or cynomolgus monkeys had low GLP-1 receptor expression in thyroid C-cells, and GLP-1 receptor agonists did not activate adenylate cyclase or generate calcitonin release in primates. Moreover, 20 months of liraglutide treatment (at >60 times human exposure levels) did not lead to C-cell hyperplasia in monkeys. Mean calcitonin levels in patients exposed to liraglutide for 2 yr remained at the lower end of the normal range, and there was no difference in the proportion of patients with calcitonin levels increasing above the clinically relevant cutoff level of 20 pg/ml. Our findings delineate important species-specific differences in GLP-1 receptor expression and action in the thyroid. Nevertheless, the long-term consequences of sustained GLP-1 receptor activation in the human thyroid remain unknown and merit further investigation.
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PMID:Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. 2020 54

Liraglutide (Victoza-Novo Nordisk), a glucagon-like peptide-1 (GLP-1) receptor agonist given by subcutaneous injection, has been approved by the FDA for treatment of patients with type 2 diabetes. It can be used alone or in addition to oral antidiabetic drugs such as metformin (Glucophage, and others) or glimepiride (Amaryl, and others). Liraglutide is not recommended for first-line therapy and is not approved for use with insulin.
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PMID:Liraglutide (Victoza) for type 2 diabetes. 2036 Jun 60

Type 2 diabetes mellitus (T2DM) is a progressive disease associated with significant morbidity and mortality. There is good evidence that intensive glycemic control reduces the development and progression of complications in patients with diabetes. In order to achieve glycemic targets, patients often require a combination of oral therapy and/or insulin in addition to lifestyle modification. Unfortunately many currently available therapies for T2DM are associated with weight gain and hypoglycemia resulting in poor compliance and subsequent worsening glycemic control. Glucagon like peptide-1 (GLP-1) is an incretin hormone secreted from the small intestine that lowers fasting and postprandial glucose through multiple mechanisms including glucose-dependent insulin secretion, reduction of glucagon secretion, delaying gastric emptying and increased satiety. Liraglutide is a long acting GLP-1 mimetic that is administered once a day by subcutaneous injection and is now licensed for the treatment of T2DM. Phase 3 clinical trials have demonstrated beneficial effects on glycemic control and weight with liraglutide therapy. Within this article, we provide an overview of pharmacology, efficacy, safety and patient experience on liraglutide in the management of T2DM.
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PMID:Liraglutide in the treatment of type 2 diabetes mellitus: clinical utility and patient perspectives. 2036 Oct 6


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