Glucagon-like peptide 1 agonists for treatment of patients with type 2 diabetes who fail metformin monotherapy: systematic review and meta-analysis of economic evaluation studies

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Abstract

Objectives

To conduct a systematic review and meta-analysis and to pool the incremental net benefits (INBs) of glucagon-like peptide 1 (GLP1) compared with other therapies in type 2 diabetes mellitus (T2DM) after metformin monotherapy failure.

Research design and methods

The study design is a systematic review and meta-analysis. We searched MEDLINE (via PubMed), Scopus and Tufts Registry for eligible cost–utility studies up to June 2018, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. We conducted a systematic review and pooled the INBs of GLP1s compared with other therapies in T2DM after metformin monotherapy failure. Various monetary units were converted to purchasing power parity, adjusted to 2017 US$. The INBs were calculated and then pooled across studies, stratified by level of country income; a random-effects model was used if heterogeneity was present, and a fixed-effects model if it was absent. Heterogeneity was assessed using Q test and I ² statistic.

Results

A total of 56 studies were eligible, mainly from high-income countries (HICs). The pooled INBs of GLP1s compared with dipeptidyl peptidase-4 inhibitor (DPP4i) (n=10), sulfonylureas (n=6), thiazolidinedione (TZD) (n=3), and insulin (n=23) from HICs were US$4012.21 (95% CI US$−571.43 to US$8595.84, I ²=0%), US$3857.34 (95% CI US$−7293.93 to US$15 008.61, I ²=45.9%), US$37 577.74 (95% CI US$−649.02 to US$75 804.50, I ²=92.4%) and US$14 062.42 (95% CI US$8168.69 to US$19 956.15, I ²=86.4%), respectively. GLP1s were statistically significantly cost-effective compared with insulins, but not compared with DPP4i, sulfonylureas, and TZDs. Among GLP1s, liraglutide was more cost-effective compared with lixisenatide, but not compared with exenatide, with corresponding pooled INBs of US$4555.09 (95% CI US$3992.60 to US$5117.59, I ²=0) and US$728.46 (95% CI US$−1436.14 to US$2893.07, I ²=0), respectively.

Conclusion

GLP1 agonists are a cost-effective choice compared with insulins, but not compared with DPP4i, sulfonylureas and TZDs.

PROSPERO registration number

CRD42018105193.

Related collections

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Previous studies have not adequately captured the heterogeneous nature of the diabetes epidemic in India. The aim of the ongoing national Indian Council of Medical Research-INdia DIABetes study is to estimate the national prevalence of diabetes and prediabetes in India by estimating the prevalence by state.

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CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM - 2018 EXECUTIVE SUMMARY.

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A1C = hemoglobin A1C; AACE = American Association of Clinical Endocrinologists; ACCORD = Action to Control Cardiovascular Risk in Diabetes; ACCORD BP = Action to Control Cardiovascular Risk in Diabetes Blood Pressure; ACEI = angiotensin-converting enzyme inhibitor; ADVANCE = Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation; AGI = alpha-glucosidase inhibitor; apo B = apolipoprotein B; ASCVD = atherosclerotic cardiovascular disease; BAS = bile acid sequestrant; BCR-QR = bromocriptine quick release; BMI = body mass index; BP = blood pressure; CCB = calcium channel blocker; CHD = coronary heart disease; CKD = chronic kidney disease; CVD = cardiovascular disease; DASH = Dietary Approaches to Stop Hypertension; DPP4 = dipeptidyl peptidase 4; eGFR = estimated glomerular filtration rate; ER = extended release; FDA = Food and Drug Administration; GLP1 = glucagon-like peptide 1; HDL-C = high-density lipoprotein cholesterol; IMPROVE-IT = Improved Reduction of Outcomes: Vytorin Efficacy International Trial; LDL-C = low-density lipoprotein cholesterol; LDL-P = low-density lipoprotein particle; Look AHEAD = Look Action for Health in Diabetes; NPH = neutral protamine Hagedorn; OSA = obstructive sleep apnea; RCT = randomized controlled trial; SU = sulfonylurea; SGLT2 = sodium glucose cotransporter-2; SMBG = self-monitoring of blood glucose; T2D = type 2 diabetes; TZD = thiazolidinedione; VADT = Veterans Affairs Diabetes Trial.

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Preservation of β-cell function: the key to diabetes prevention.

R Ghani, Ralph A. DeFronzo (2011)

The Centers for Disease Control and Prevention estimates that there are approximately 79,000,000 individuals in the United States with prediabetes [impaired glucose tolerance (IGT) and/or impaired fasting glucose] and that approximately 40-50% will progress to type 2 diabetes mellitus (T2DM) during their lifetime. Therefore, treatment of high-risk IGT individuals to prevent T2DM has important medical, economic, social, and human implications. Individuals in the upper tertile of IGT are maximally/near-maximally insulin resistant, have lost 70-80% of their β-cell function, and have approximately a 10% incidence of diabetic retinopathy. Therefore, preservation of the remaining 20-30% of β-cell function is critical to prevent future development of T2DM. We searched MEDLINE from 2000 to the present to identify placebo-controlled trials in which individuals with IGT received pharmacological therapy to prevent progression to diabetes. Lifestyle modification reduces IGT conversion to T2DM, but it is difficult to implement and maintain. Moreover, 40-50% of IGT subjects progress to T2DM despite weight loss. In contrast, pharmacological intervention with medications that reverse known pathophysiological abnormalities (β-cell dysfunction and insulin resistance) uniformly prevents IGT progression to T2DM. Thiazolidinediones reduce IGT conversion to diabetes by approximately 50-70%. Metformin in the U.S. Diabetes Prevention Program reduced the development of T2DM by 31% and has been recommended by the American Diabetes Association. Because glucagon-like peptide-1 analogs augment insulin secretion, preserve β-cell function, and promote weight loss, they may be efficacious in preventing IGT progression to T2DM. Pharmacological intervention with a variety of agents (thiazolidinediones, metformin, acarbose, glucagon-like peptide-1 analogs) consistently reduces the rate of conversion of IGT to T2DM.

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Author and article information

Journal

Journal ID (nlm-ta): BMJ Open Diabetes Res Care

Journal ID (iso-abbrev): BMJ Open Diabetes Res Care

Journal ID (hwp): bmjdrc

Journal ID (publisher-id): bmjdrc

Title: BMJ Open Diabetes Research & Care

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Electronic): 2052-4897

Publication date Collection: 2020

Publication date (Electronic): 19 July 2020

Volume: 8

Issue: 1

Electronic Location Identifier: e001020

Affiliations

[1 ]departmentNon-Communicable Diseases , ICMR-National Institute of Epidemiology , Chennai, India

[2 ]departmentMahidol University Health Technology Assessment (MUHTA) Graduate Program , Mahidol University , Bangkok, Thailand

[3 ]departmentSocial and Administrative Pharmacy Division, Department of Pharmacy , Faculty of Pharmacy, Mahidol University , Bangkok, Thailand

[4 ]departmentEpidemiology Group , ICMR-National Institute of Virology , Pune, India

[5 ]departmentDepartment of Family Medicine, Faculty of Medicine Ramathibodi Hospital , Mahidol University , Bangkok, Thailand

[6 ]departmentCollege of Pharmacy , University of Utah , Salt Lake City, Utah, USA

[7 ]departmentCentre for Clinical Epidemiology and Biostatistics, Hunter Medical Research Institute, School of Medicine and Public Health , University of Newcastle , New Lambton, New South Wales, Australia

[8 ]departmentDivision of Medicine , John Hunter Hospital , New Lambton, New South Wales, Australia

[9 ]departmentDepartment of Clinical Epidemiology and Biostatistics, Faculty of Medicine Ramathibodi Hospital , Mahidol University , Bangkok, Thailand

Author notes

[Correspondence to ] Dr Usa Chaikledkaew; usa.chi@ 123456mahidol.ac.th

Author information

Bhavani Shankara Bagepally http://orcid.org/0000-0003-0856-767X

Usa Chaikledkaew http://orcid.org/0000-0001-9457-9823

Article

Publisher ID: bmjdrc-2019-001020

DOI: 10.1136/bmjdrc-2019-001020

PMC ID: 7371226

PubMed ID: 32690574

SO-VID: b8a03e00-1429-4cea-863f-0ccc0dc21390

License:

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

History

Date received : 04 November 2019

Date revision received : 26 February 2020

Date accepted : 08 June 2020

Custom metadata

special-feature unlocked

Keywords: glucagon-like peptide-1 (glp-1),economic analysis,cost-effectiveness,meta-analysis

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Keywords: glucagon-like peptide-1 (glp-1), economic analysis, cost-effectiveness, meta-analysis