Comparison Review of Short-Acting and Long-Acting Glucagon-like Peptide-1 Receptor Agonists (original) (raw)
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Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are well established as effective treatments for patients with type 2 diabetes. GLP-1 RAs augment insulin secretion and suppress gluca-gon release via the stimulation of GLP-1 receptors. Although all GLP-1 RAs share the same underlying mechanism of action, they differ in terms of formulations, administration, injection devices and dosages. With six GLP-1 RAs currently available in Europe (namely, immediate release exenatide, lixisenatide, liraglutide; prolonged-release exenatide, dulaglutide and semaglutide), each with its own characteristics and administration requirements, physicians caring for patients in their routine practice face the challenge of being cognizant of all this information so they are able to select the agent that is most suitable for their patient and use it in an efficient and optimal way. The objective of this review is to bring together practical information on the use of these GLP-1 RAs that reflects their approved use.
GLP-101: A Diabetes Educator’s Guide to Glucagon-Like-Peptide-1 Receptor Agonists
AADE in Practice, 2019
acting agents have come to the market that require once-daily dosing, such as lixisenitide (Adlyxin) and liraglutide (Victoza, Saxenda), or once-weekly dosing, including dulaglutide (Trulicity), extendedrelease exenatide (Bydureon, Bydureon BCise), and semaglutide (Ozempic). 1 While liraglutide as the brand name Saxenda is not indicated for the management of type 2 diabetes, it is FDA approved for weight management in combination with a reduced-calorie diet and increased physical activity. 2 An additional long-acting product albiglutide (Tanzeum) was previously available and withdrawn from the market in 2018 due to lack of prescribing. 3 There have also been basal insulin/GLP-1 combination products developed: insulin degludec/liraglutide (Xultophy 100/3.6) and insulin glargline/lixisenatide (Soliqua 100/33). Currently, there are multiple phase 3 trials ongoing for semaglutide as the first potential oral GLP-1 receptor agonist. 4 Mechanism GLP-1 agonists mimic the body's natural GLP-1, an incretin hormone with a multitude of actions.
Review of head-to-head comparisons of glucagon-like peptide-1 receptor agonists
Diabetes, Obesity and Metabolism, 2015
Currently, six glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for treating type 2 diabetes. These fall into two classes based on their receptor activation: short-acting exenatide twice daily and lixisenatide once daily; and longer-acting liraglutide once daily, exenatide once weekly, albiglutide once weekly and dulaglutide once weekly. The phase III trial of a seventh GLP-1RA, taspoglutide once weekly, was stopped because of unacceptable adverse events (AEs). Nine phase III head-to-head trials and one large phase II study have compared the efficacy and safety of these seven GLP-1RAs. All trials were associated with notable reductions in glycated haemoglobin (HbA1c) levels, although liraglutide led to greater decreases than exenatide formulations and albiglutide, and HbA1c reductions did not differ between liraglutide and dulaglutide. As the short-acting GLP-1RAs delay gastric emptying, they have greater effects on postprandial glucose levels than the longer-acting agents, whereas the longer-acting compounds reduced plasma glucose throughout the 24-h period studied. Liraglutide was associated with weight reductions similar to those with exenatide twice daily but greater than those with exenatide once weekly, albiglutide and dulaglutide. The most frequently observed AEs with GLP-1RAs were gastrointestinal disorders, particularly nausea, vomiting and diarrhoea. Nauseaoccurred less frequently, however, with exenatide once weekly and albiglutide than exenatide twice daily and liraglutide. Both exenatide formulations and albiglutide may be associated with higher incidences of injection-site reactions than liraglutide and dulaglutide. GLP-1RA use in clinical practice should be customized for individual patients, based on clinical profile and patient preference. Ongoing assessments of novel GLP-1RAs and delivery methods may further expand future treatment options.
Diabetes, Obesity and Metabolism, 2011
Incretin-based therapies, such as the injectable glucagon-like peptide-1 (GLP-1) receptor agonists and orally administered dipeptidyl peptidase-4 (DPP-4) inhibitors, have recently been introduced into clinical practice. At present, the GLP-1 receptor agonists need to be administered once or twice daily. Several once-weekly GLP-1 receptor agonists are in phase 3 development. This review examines the efficacy, safety and perspective for the future of the once-weekly GLP-1 receptor agonists: exenatide once weekly, taspoglutide, albiglutide, LY2189265 and CJC-1134-PC, and compared them to the currently available agonists, exenatide BID and liraglutide QD. A greater reduction in haemoglobin A1c (HbA1c) and fasting plasma glucose was found with the once-weekly GLP-1 receptor agonists compared with exenatide BID, while the effect on postprandial hyperglycaemia was modest with the once-weekly GLP-1 receptor agonist. The reduction in HbA1c was in most studies greater compared to oral antidiabetic drugs and insulin glargine. The reduction in weight did not differ between the short-and long-acting agonists. The gastrointestinal side effects were less with the once-weekly agonists compared with exenatide BID, except for taspoglutide. Antibodies seem to be most frequent with exenatide once weekly, while hypersensitivity has been described in few patients treated with taspoglutide. Injection site reactions differ among the long-acting GLP-1 receptor agonists and are observed more frequently than with exenatide BID and liraglutide. In humans, no signal has been found indicating an association between the once-weekly agonists and C-cell cancer. The cardiovascular safety, durability of glucose control and effect on weight will emerge from several ongoing major long-term trials. The once-weekly GLP-1 receptor analogues are promising candidates for the treatment of type 2 diabetes, although their efficacy may not be superior to once-daily analogue liraglutide.
Diabetes, Obesity and Metabolism, 2015
To assess the efficacy and safety of recently approved once-weekly glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials comparing any GLP-1 RA licensed for once-weekly dosing (albiglutide, dulaglutide or exenatide extended release) with placebo or other antidiabetic agents. We searched Medline, Embase, the Cochrane Library and grey literature for articles published up to December 2014 and extracted data in duplicate. Results: In our systematic review we included 33 trials with a total of 16 003 participants. Compared with placebo the change in glycated haemoglobin (HbA1c) concentration was −0.66% [six studies; 95% confidence interval (CI) −1.14 to −0.19; I 2 = 88%] with albiglutide, and −1.18% (seven studies; 95% CI −1.34 to −1.02; I 2 = 65%) with dulaglutide. Based on data from placebo-controlled trials, we did not detect statistically significant weight-sparing benefits for albiglutide or dulaglutide. Compared with other antidiabetic agents, once-weekly GLP-1 RAs outperformed sitagliptin, daily exenatide and insulin glargine in terms of HbA1c-lowering (mean differences −0.40%; 95% CI −0.66 to −0.14; I 2 = 85%, −0.44%; 95% CI −0.58 to −0.29; I 2 = 40% and −0.28; 95% CI −0.45 to −0.10; I 2 = 81%, respectively). The main adverse effects of treatment included gastrointestinal and injection site reactions. Conclusions: Given their dosing scheme and overall efficacy and safety profile, once-weekly GLP-1 RAs are a convenient therapeutic option for use as add-on to metformin.
Glucagon like peptide 1 receptor agonists: a therapy for diabetes management
Ces Medicina, 2018
Introduction: Glucagon-like peptide 1 agonists inhibit glucose-dependent glucagon secretion, decrease gastric emptying and appetite through neural mechanisms, contribute to glucose regulation and show reduction in glycated hemoglobin A. Methods: A bibliographic search was made on Medli-ne® about pharmacology of the agonist glucagon-like peptide-1 receptor , Liraglutide, Lixisenatide, Albiglutide, Exenatide, Exenatide with long-acting release. Results: The GLP1 receptor agonist are agents involved with glycemic balance, weight loss induction and are associated with lower risk of hypoglycemia. They have shown efficacy in the treatment of hypoglycemia in patients with type-2 diabetes. Conclusions: GLP1 receptor agonist are part of the therapies for diabetes that have shown benefits in metabolic control, effectiveness in weight reduction and changes in glycated hemoglobin. More studies are needed to evaluate its long-term safety.
Therapeutics and Clinical Risk Management
Failure of secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) plays a prominent role in type 2 diabetes, and restoration of GLP-1 action is an important therapeutic objective. Although the short duration of action of GLP-1 renders it unsuited to therapeutic use, 2 long-acting GLP-1 receptor agonists, exenatide and liraglutide, represent a significant advance in treatment. In controlled trials, both produce short-term glucose-lowering effects, with the reduction in hemoglobin A(1c) of up to 1.3%. These responses are often superior to those observed with additional oral agents. However, unlike sulfonylureas, thiazolidinediones, or insulin, all of which lead to significant weight gain, GLP-1 receptor agonists uniquely result in long-term weight loss of around 5 kg, and higher doses may enhance this further. Reduction in blood pressure of 2-7 mm Hg also has been observed. Both drugs produce transient mild gastrointestinal side effects; although mild hypoglycemia can occur...
European Journal of Internal Medicine, 2014
A growing body of data, guideline recommendations, algorithms, and position papers supports the use of glucagon-like peptide-1 (GLP-1) receptor agonists in type 2 diabetes (T2D), given their beneficial effects on glycemic control, weight, lipid parameters, and blood pressure, and low risk for hypoglycemia when used in patients who have not achieved glycemic goals with metformin and lifestyle interventions. Exciting new evidence continues to emerge, showing the utility of certain GLP-1 receptor agonists to decrease incident cardiovascular (CV) outcomes, and to bolster glycemic control when combined with other antihyperglycemic therapies, including basal insulin. The recent availability of fixed-ratio GLP-1 receptor agonist and basal insulin coformulations-and a new, first-ever, indication for the use of a GLP-1 receptor agonist (liraglutide) to reduce the risk of major adverse CV events (MACE) in adults with T2D and established cardiovascular disease (CVD)-increase options for improved care. In addition, semaglutide (another GLP-1 receptor agonist with positive CV outcomes data) received FDA approval in December 2017 with an indication to improve glycemic control in adults with T2D. These new developments and continuously emerging CV outcomes data should be considered in determining how GLP-1 receptor agonists may be best used in clinical practice. This Q&A presentation with 2 expert endocrinologists provides a pragmatic approach to inform the selection and use of GLP-1 receptor agonists based on the rapidly evolving evidence.
Overview of Glucagon-like Peptide-1 Receptor Agonists
Home healthcare now
Type 2 diabetes mellitus is an increasingly prevalent disease in the United States and globally. Multiple pharmacologic therapies are typically required over time to achieve and maintain target blood glucose levels. When first-line oral medications such as metformin (Glucophage) are not effective in achieving desired glycosylated hemoglobin (HbA1C) levels, glucagon-like peptide-1 receptor agonists may be used. This article provides an overview of this class of agents and provides implications for home healthcare clinicians.