GLP-1 receptor agonists in the treatment of type 2 diabetes: role and clinical experience to date (original) (raw)
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Current Issues in GLP-1 Receptor Agonist Therapy for Type 2 Diabetes
Endocrine Practice, 2012
Abbreviations: A1C = glycated hemoglobin; ABCD = Association of British Clinical Diabetologists; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BID = twice daily; BMI = body mass index; BNP = brain natriuretic peptide; CIs = confidence intervals; CrCl = creatinine clearance; DAWN Trial = Diabetes Attitudes, Wishes and Needs Trial; DPP-4 = dipeptidyl peptidase-4; DTSQ-s: Diabetes Treatment Satisfaction Questionnairestatus; EASD = European Association for the Study of Diabetes; ER = extended release; ESRD = end-stage renal disease; EXN = exenatide; FAERS = FDA Adverse Event Reporting System; FDA = United States Food and Drug Administration; FPG = fasting plasma glucose; GI = gastrointestinal; GIP = glucosedependent insulinotropic polypeptide; GLAR = insulin glargine; GLP-1 = glucagon-like peptide-1; GLP-1 RA = glucagon-like peptide-1 receptor agonist; HOMA-B: homeostatic model assessment-β-cell function; HRQL = healthrelated quality of life; hs-CRP = high-sensitivity C-reactive protein; IDET = insulin detemir; IMT = intima-media thickness; IWQOL-Lite: Impact of Weight on Quality of Life-Lite; LEAD Trials = Liraglutide Effect and Action in Diabetes Trials; LIRA = liraglutide; MEN 2 = multiple endocrine neoplasia syndrome type 2; MET = metformin; MTC = medullary thyroid carcinoma; NAFLD = nonalcoholic fatty liver disease; NASH = nonalcoholic steatohepatitis; NICE = National Institute for Clinical Excellence; NIH = National Institutes of Health; OAD = oral antidiabetic agent; PAI-1 = plasminogen activator inhibitor-1; PBO = placebo; PPG = postprandial glucose; PROs = patient-reported outcomes; RA = receptor agonist; RCT = randomized controlled trial; RI = renal impairment; RORs = reporting odds ratios; SCALE = Satiety and Clinical Adiposity -Liraglutide Evidence in Non-Diabetic and Diabetic Subjects; STEMI = ST segment elevation myocardial infarction; SU = sulfonylurea; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus; TZD = thiazolidinedione
GLP-1RA for glycaemic control and obesity as add on therapy for type 2 diabetes
Mediterrenean Journal of Pharmacy and Pharmaceutical Sciences, 2023
Diabetes mellitus (DM) is a complex and chronic illness requiring continuous medical care. Type 2 diabetes (T2D) is commonly associated with obesity, hypertension, and a tendency to develop thrombosis, and increase risk of cardiovascular diseases (CVD). Diabesity is a term used to indicate an coexistence of obesity and DM. Diabesity increases as obesity is an emerging epidemic of modern societies, the coincidence with DM is also rising, so a joint plan of anti-obesity and anti-hyperglycemia for the management approaches. Therefore, this study aimed to identify the impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on bodyweight and glycemic response in obese Libyan patients with T2D at the National Diabetes Centre in Tripoli, between July 2013 and May 2022. This prospective study included obese adults with T2D who were newly prescribed GLP-1RA therapy for six months with dulaglutide once weekly or liraglutide once daily. The study included 170 diabetic patients were started on GLP1-RA as add on therapy to their treatment, with a regular follow up with dietitian and their physicians to adjusted their glucose lowering medications, than comparing the effect of these agents on bodyweight and the level of glycated hemoglobin before and after 24 weeks of treatment. Most of the patients (n = 99, 58.23%) were in the age period from 54 to 74 years old and 101 of whom were female subjects (59.4%), with a mean duration of DM equal to 8.8 ± 7.3 years. The patients were divided randomly into two groups, the first group included 110 patients who received liraglutide pens showed a significantly reduction in HbA1c from 9.6% (± 1.54) to 7.4% (± 1.03) by p < 0.001 and a significantly weight loss from 88.3 kg (± 10.68) to 80.8 kg (± 11.83) by p < 0.001. The reported adverse events were in 23 cases of minor hypoglycemia due to gastrointestinal upset. The other group included 60 patients for dulaglutide pens showed a significant decrease in HbA1c = 9.6% (± 1.54) to 7.1% (± 1.2) by p < 0.05 and a significant reduction of bodyweight from 88.3 kg (± 10.68) to 83.8 kg (± 16.3) by p < 0.05. The reported adverse events were mild transient gastrointestinal distressed for initial week of start than subside with regular intake. Whereas, 115 patients (67.6%) with HbA1c above 10.0% before start therapy, no patient with HbA1c above 10.0% after six months of both GLP-RA agents therapy. Thus, uses of GLP-RA as add on therapy for obese patients with T2D significantly improved the glycaemic control with less hypoglycaemia, accordingly, reduce insulin requirement for the blood glucose control and loss in bodyweight. It can thus be concluded that GLP-1RA therapy is an effective treatment option when used in the obese patients with DM.
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.
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.
The evolving world of GLP-1 agonist therapies for type 2 diabetes
Therapeutic advances in endocrinology and metabolism, 2010
The glucagon-like peptide-1 (GLP-1) agonist drugs have attractions as a treatment for type 2 diabetes since they positively alter a number of key pathophysiological defects. These include increasing insulin release, reducing glucagon release, slowing gastric emptying and reducing food intake. In numerous clinical trials these agents have been shown to reduce DCCT-aligned HbA(1c) between 0.8% and 1.1% in patients with moderately controlled type 2 diabetes, whilst also being associated with some weight loss. Whilst medium-term safety and side-effect profiles are now well established, there are as yet no long-term studies on the safety of this group of drugs. The place of the GLP-1 agonists in the treatment paradigm for type 2 diabetes will evolve over the next decade.
Defining the role of GLP-1 receptor agonists for individualized treatment of type 2 diabetes
With the advent of dipeptidyl peptidase (DPP)-4 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) over the past decade, incretin therapy has become established as an important treatment strategy for type 2 diabetes mellitus (T2DM), with an efficacy and safety profile distinct from that of other anti-hyperglycemic agents. However, our understanding of the optimal clinical use of incretins remains incomplete. This review focuses on the use of GLP-1 RAs in the treatment of T2DM, with reference to the differing dominant mechanisms of action between short- and long-acting GLP-1 RAs and the clinical implications of this difference. The role of GLP-1 and the effects of GLP-1 RAs in various organs other than the pancreas will also be discussed.
A review of the new GLP-1 receptor agonist/basal insulin fixed-ratio combination products
Therapeutic Advances in Endocrinology and Metabolism
There have been several new treatment approaches established for the management of hyperglycemia in type 2 diabetes (T2D), with treatment guidelines listing both glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and basal insulin therapies as considerations for patients who have failed to control their blood glucose with oral antidiabetic agents. New studies have highlighted the importance of initiating combination therapy earlier in the T2D disease process to avoid clinical inertia and prevent the long-term complications arising from uncontrolled diabetes. Until recently, both GLP-1 RAs and basal insulin therapies were only available as single agents, but there are now two combination pen devices that deliver both a GLP-1 RA and basal insulin simultaneously. This article reviews the current clinical evidence evaluating the use of these combination GLP-1 RA/basal insulin preparations to treat T2D, presents both potential benefits as well as possible downsides with the use of the...
Clinical Diabetology
Objective: Despite the benefit-risk ratio favoring glucagon-like peptide-1 receptor agonists (GLP-1 RAs), knowledge and awareness is lacking among patients and physicians, particularly in India. The current review provides an overview of GLP-1 RAs and the opinion of a group of healthcare practitioners (HCPs) and independent consultants across India on the evidence for using GLP-1 RAs and its applicability to the Indian population. Materials and methods: A panel of eight HCPs met virtually on December 12-13, 2020 met as part of the Diabetes Research Society (DIABAID). They examined and critically discussed the current research on the use of GLP-1 RAs in the management of T2DM. Results: The panel observed that recent diabetes guidelines and recommendations have shifted toward a more individualised and CV risk-focused approach to T2DM management. They proposed that 1) GLP-1 RAs are ideal cardio-metabolic drugs that address multiple aspects of the T2DM; 2) to bring up GLP-1 RAs as early treatment option in discussions with patients; 3) in T2DM patients with a high CV risk or established ASCVD, CKD, or HF, GLP-1 RAs with proven CVD benefits should be initiated; 4) including oral semaglutide in international treatment recommendation guidelines to improve patient and HCP understanding and adaptability; and 5) patient-physician dialogues will be critical in incorporating GLP-1 RAs earlier in the treatment paradigm for effective T2DM management. Conclusions: The recommendations on using GLP-1 RAs and the associated benefits and risks of these drugs comprise essential considerations for using such medications in the Indian population. (Clin Diabetol 2022, 11; 4: 269-293) Keywords: glucagon-like peptide-1 receptor agonists, India, opinion, oral semaglutide, type 2 diabetes mellitus This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially. this review article is accompanied by an editorial, see page 215.
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.
Real-world GLP-1 RA therapy in type 2 diabetes: A long-term effectiveness observational study
Endocrinology, Diabetes & Metabolism, 2018
The glucagon-like peptide-1 receptor agonist (GLP-1 RA) pharmacological class is increasingly becoming a widely prescribed therapy in type 2 diabetes (T2D) based upon a robust hypoglycaemic effect mediated through stimulation of β-cells aimed to enhance insulin secretion in a glucose-dependent manner, while simultaneously suppressing the secretion of glucagon from α-cells. Besides, GLP-1 RAs are able to prolong gastric emptying and induce satiety with a potential to reduce body weight, a major factor contributing to insulin resistance and hyperglycaemia in T2DM. 1,2 Clinical trials have demonstrated that GLP-1 RA therapy is able to reduce glycated