A Review of Practical Issues on the Use of Glucagon- Like Peptide-1 Receptor Agonists for the Management of Type 2 Diabetes (original) (raw)
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Comparison Review of Short-Acting and Long-Acting Glucagon-like Peptide-1 Receptor Agonists
Diabetes Therapy, 2015
Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) are useful tools for treating type 2 diabetes mellitus. In their recent position statement, the American Diabetes Association and European Association for the Study of Diabetes recommend GLP1-RAs as add-on to metformin when therapeutic goals are not achieved with monotherapy, particularly for patients who wish to avoid weight gain or hypoglycemia. GLP1-RAs differ substantially in their duration of action, frequency of administration and clinical profile. Members of this class approved for clinical use include exenatide twice-daily, exenatide once-weekly, liraglutide and lixisenatide once-daily. Recently, two new once-weekly GLP1-RAs have been approved: dulaglutide and albiglutide. This article summarizes properties of short-and long-acting GLP-1 analogs, and provides useful information to help choose the most appropriate compound for individual patients.
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.
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.
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.
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.
GLP-1 receptor agonists for type 2 diabetes
The Lancet, 2009
The ever-increasing number of drugs available to treat type 2 diabetes and the complexity of patients with this condition present a constant challenge when it comes to identifying the most appropriate treatment approach. The more recent glucagon-like peptide-1 receptor agonists (GLP-1RAs) are non-insulin injectable options for the management of type 2 diabetes. Effective at improving glycaemic control with a low intrinsic risk of hypoglycaemia and the potential for weight reduction, this agent class is an important addition to the prescribing armamentarium. However, understanding their place in therapy may prove confusing for many primary care practitioners, especially given the common belief that 'injectables' are a last-resort treatment option, which puts them at risk of being niched alongside insulin. This review summarises the clinical evidence for GLP-1RAs and how they compare to other glucose-lowering agents in managing type 2 diabetes. It also provides practical and case-driven opinions and recommendations on the optimal use of GLP-1RAs by discussing important patient factors and clinical considerations that will help to identify those who are most likely to benefit from this class of agents.
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.
Diabetes, Obesity and Metabolism, 2016
Since 2005, several glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been approved to treat people with type 2 diabetes. These agents are considered for use at the same point in the treatment paradigm as basal insulins. A comprehensive comparison of these drug classes, therefore, can help inform treatment decisions. This systematic review and metaanalysis assessed the clinical efficacy and safety of GLP-1 RAs compared with basal insulins. Materials and methods: MEDLINE, EMBASE, CENTRAL and PubMed databases were searched. Randomized clinical trials (RCTs) of ≥16 weeks' duration comparing GLP-1 RAs vs basal insulins in adults with type 2 diabetes inadequately controlled with oral antihyperglycemic drugs were included. Data on the change from baseline to 26 weeks (AE10 weeks) of treatment in hemoglobin A1c (HbA1c) and weight, as well as the proportion of patients experiencing hypoglycaemia, were extracted. Fixed-effect pairwise meta-analyses were conducted where data were available from ≥2 studies. Results: Fifteen RCTs were identified and 11 were meta-analysed. The once-weekly GLP-1 RAs, exenatide long acting release (LAR) and dulaglutide, led to greater, statistically significant mean HbA1c reductions vs basal insulins (exenatide: −0.31% [95% confidence interval −0.42, −0.19], dulaglutide: −0.39% [−0.49, −0.29]) whilst once-daily liraglutide and twice-daily exenatide did not (liraglutide: 0.06% [−0.06, 0.18], exenatide: 0.01% [−0.11, 0.13]). Mean weight reduction was seen with all GLP-1 RAs while mean weight gain was seen with basal insulins. Interpretation of the analysis of hypoglycaemia was limited by inconsistent definitions and reporting. Because of the limited number of available studies sensitivity analyses to explore heterogeneity could not be conducted. Conclusions: Although weight reduction is seen with all GLP-1 RA's, only the once-weekly agents, exenatide LAR and dulaglutide, demonstrate significant HbA1c reductions when compared to basal insulins.
GLP-1 receptor agonists in the treatment of type 2 diabetes: role and clinical experience to date
Postgraduate Medicine
Glucagon-like peptide-1 (GLP-1) is a hormone of the incretin system responsible for a variety of glucoregulatory effects, including glucose-dependent secretion of insulin and inhibition of glucagon release, the effects of which are impaired in people with type 2 diabetes (T2D). Targeting this deficiency using GLP-1 receptor agonists (GLP-1RAs) is a well-established approach in T2D, with over a decade of clinical experience now accrued. This article reviews the evidence for subcutaneous GLP-1RAs and their role in T2D treatment, and explores the rationale for an oral GLP-1RA from a primary care perspective. Clinical trials and real-world studies with subcutaneous GLP-1RAs indicate that these agents have good glycated hemoglobin (HbA 1c)-lowering efficacy, an inherently low potential for hypoglycemia, and reduce body weight. Cardiovascular outcomes trials have established cardiovascular safety, and three GLP-1RAs have been proven to reduce the risk of major adverse cardiovascular events (MACE) in patients with established cardiovascular disease or at high cardiovascular risk. The most common adverse events associated with GLP-1RAs are gastrointestinal effects, which tend to occur soon after initiation and decline over time. T2D treatment guidelines recommend GLP-1RAs as a therapeutic option in various settings, including in those patients: i) not achieving HbA 1c targets after first-line metformin and lifestyle modifications; ii) at high risk of/with established atherosclerotic cardiovascular disease (regardless of HbA 1c ; GLP-1RAs of proven benefit); iii) not achieving HbA 1c targets on basal insulin if not already receiving a GLP-1RA. Despite the known benefits of GLP-1RAs, adherence and persistence rates are suboptimal, potentially due in part to injection-related concerns. With some patients having a preference for oral medications, the development of an oral GLP-1RA is a logical approach to improving treatment options for patients with T2D. Co-formulation of semaglutide with an absorption enhancer has enabled the development and recent approval of the first oral GLP-1RA, oral semaglutide, which has the potential to expand use of GLP-1RAs in clinical practice.
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 2012
The prevalence of obesity and diabetes continues to rise in the US. Glucagon-like peptide-1 receptor agonist (GLP-1RA) is an effective treatment option for type 2 diabetes mellitus (T2DM) that promotes weight loss. Common and effective treatment options added to metformin therapy (basal insulin, sulfonylureas, and pioglitazone) contribute to weight gain, which makes the addition of GLP-1RAs advantageous. Exenatide was the first agent in this class and has recently been approved for use in combination with insulin glargine by the US Food and Drug Administration and the European Medicines Agency. Until recently, there was a lack of data examining basal insulin combined with these agents. The main purpose of this article is to review the prospective interventional data on the safety and efficacy of GLP-1RAs (exenatide, liraglutide, albiglutide, lixisenatide) combined with basal insulin therapy in nonpregnant adults with T2DM. Databases searched were PubMed, Cochrane Central Register of Controlled Trials and the Database of Systematic Reviews (inception to January 2012). Abstracts presented at relevant diabetes and endocrine meetings from 2009 to 2011 were also reviewed, as were reference lists of identified publications. A total of five studies met the criteria and were included in the review. Data from these studies demonstrated that this combination therapy offers advantages for the treatment of diabetes, such as additional lowering of A1c without major risk for hypoglycemia, lower basal insulin requirements, decreased postprandial glucose levels (with or without fasting plasma glucose decreases), and weight loss, or at the very least, less weight gain. However, the gastrointestinal side effects and high cost of these agents may limit their use. This review demonstrates that adding a GLP-1RA to an existing basal insulin regimen is a reasonable treatment strategy in nonpregnant adult patients with T2DM.