Glucagon-like peptide-1 receptor agonists: a systematic review of comparative effectiveness research

Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy Dovepress open access to scientific and medical research Review Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy downloaded from https://www.dovepress.com/ by 54.37.163.172 on 12-Jul-2018 For personal use only. Open Access Full Text Article Glucagon-like peptide-1 receptor agonists: a systematic review of comparative effectiveness research This article was published in the following Dove Press journal: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 4 April 2017 Number of times this article has been viewed Philip A Levin 1 Hiep Nguyen 2 Eric T Wittbrodt 2 Seoyoung C Kim 3 1 Bay West Endocrinology Associates, Baltimore, MD, 2Health Economics and Outcomes Research, AstraZeneca, Wilmington, DE, 3Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA Introduction Correspondence: Seoyoung C Kim Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, 1620 Tremont Street, Suite 3030, Boston, MA 02120, USA Tel +1 617 278 0930 Fax +1 617 232 8602 Email Diabetes mellitus is a chronic disease affecting a substantial proportion of the population.1 In adults (age 20–79 years), the 2015 prevalence of diabetes worldwide was estimated at 8.8%, with type 2 diabetes (T2D) comprising 91% of cases.2 By 2030, diabetes is expected to be the seventh leading cause of death.3 Several classes of glucose-lowering agents are currently available for the treatment of T2D, each with different mechanisms of action and therapeutic effects. Glucagonlike peptide-1 receptor agonists (GLP-1RAs) are a class of glucose-lowering drugs that act on the glucagon-like peptide-1 (GLP-1) receptor on pancreatic beta cells and increase insulin secretion, decrease glucagon secretion, slow gastric emptying, and increase satiety; clinical trials have shown that GLP-1RAs decrease body weight, 123 submit your manuscript | www.dovepress.com Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2017:10 123–139 Dovepress © 2017 Levin et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://dx.doi.org/10.2147/DMSO.S130834 Powered by TCPDF (www.tcpdf.org) Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) act by increasing insulin secretion, decreasing glucagon secretion, slowing gastric emptying, and increasing satiety. Objective: Published evidence directly comparing GLP-1RAs with other approved treatments for type 2 diabetes (T2D) was systematically reviewed. Methods: A literature search was performed using MEDLINE and Embase databases to identify papers comparing GLP-1RAs with other classes of glucose-lowering therapy in patients with T2D. Results: Of the 1303 papers identified, 57 met the prespecified criteria for a high-quality clinical trial or retrospective study. The efficacy and tolerability of approved GLP-1RAs (exenatide twice daily or once weekly, dulaglutide, liraglutide, lixisenatide, and albiglutide) were compared with insulin products (23 prospective studies + seven retrospective studies), dipeptidyl peptidase-4 inhibitors (11 prospective studies + three retrospective studies), sulfonylureas (nine prospective studies + one retrospective study), thiazolidinediones (five prospective studies), and metformin (two prospective studies). GLP-1RAs are effective as a second-line therapy in improving glycemic parameters in patients with T2D. Reductions in glycated hemoglobin from baseline with GLP-1RAs tended to be greater or similar compared with insulin therapy. GLP-1RAs were consistently more effective in reducing body weight than most oral glucose-lowering drugs and insulin and were associated with lower hypoglycemia risk versus insulin or sulfonylureas. GLP-1RAs improved cardiovascular risk factors, and preliminary data suggest they improve cardiovascular outcomes in patients with T2D compared with oral glucose-lowering drugs. However, results from ongoing studies are awaited to confirm these early findings. Conclusion: This systematic review found that GLP-1RAs are an effective class of glucoselowering drugs for T2D. Keywords: antidiabetic drugs, randomized controlled trials, retrospective, type 2 diabetes Dovepress Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy downloaded from https://www.dovepress.com/ by 54.37.163.172 on 12-Jul-2018 For personal use only. Levin et al Exenatide once weekly (QW) was associated with significantly greater (P < 0.001) reductions in glycated hemoglobin (HbA1c) and fasting glucose (FG) compared with sitagliptin after 26 weeks in the Diabetes Therapy Utilization: Researching Changes in A1C, Weight and Other Factors Through Intervention with Exenatide Once Weekly (DURATION)-2 and DURATION-4 studies (Table 1).8,9 Although both exenatide QW and sitagliptin recipients lost weight, patients receiving exenatide QW had significantly greater weight loss from baseline.8,9 One study comparing exenatide twice daily (BID) with sitagliptin found that exenatide BID recipients had a reduction in FG similar to sitagliptin recipients, but a significantly greater reduction in weight.7 In the Assessment of Weekly Administration of LY2189265 in Diabetes (AWARD)-5 study, after 52 weeks of treatment, reductions from baseline in HbA1c, FG, and weight were significantly greater with dulaglutide than with sitagliptin (Table 1).10 These benefits were sustained over 104 weeks of treatment.11 Generally, liraglutide-treated patients had greater or similar reductions from baseline in HbA1c, FG, and weight compared with sitagliptin- or vildagliptin-treated patients (Table 1).12–14,16 In an open-label extension study, patients switching from sitagliptin to liraglutide had further reductions in these parameters.15 When administered for 24 weeks, lixisenatide produced reductions from baseline in HbA1c and FG that were similar to sitagliptin (Table 1);17 however, weight loss was significantly greater among lixisenatide versus sitagliptin recipients. Hypoglycemia rates in patients receiving GLP-1RAs or DPP-4is were low, with only one instance of major/ severe hypoglycemia reported across all studies (in a patient receiving liraglutide 1.2 mg).13,14 In studies of exenatide QW, minor hypoglycemia rates ranged from 1% to 3.6% with exenatide QW, with th (...truncated)