Real-world prevalence of the inclusion criteria for the LEADER trial: Data from a national general practice network

William Hinton, Michael Feher, Neil Munro, Megan Walker, Simon de Lusignan, William Hinton, Michael Feher, Neil Munro, Megan Walker, Simon de Lusignan

Abstract

Aims: To explore the prevalence and describe the clinical characteristics of people with type 2 diabetes with a similar cardiovascular (CV) profile to that of the LEADER trial participants in a primary care setting in England.

Materials and methods: In this cross-sectional analysis, using the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network database, we identified people with type 2 diabetes meeting the LEADER inclusion criteria. We identified people's CV risk factors using computerized medical records. Additionally, we assessed the prescription pattern of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in this cohort.

Results: Of 1 275 461 adults, we identified 84 394 with type 2 diabetes, of whom 14 000 (16.6%) met the LEADER inclusion criteria for established or high-risk CV disease (RCGP RSC-CVD group). The LEADER cohort was younger than the RCGP RSC-CVD group (64.2 vs 73.2 years), had higher mean glycated haemoglobin (71.6 vs 67.1 mmol/mol) and blood pressure (BP) values (systolic BP: 135.9 vs 132.9 mmHg; diastolic BP: 77.2 vs 72.7 mmHg), and a higher mean body mass index (32.5 vs 30.9 kg/m2 ). In the RCGP RSC-CVD group, only 1215 people (8.7%) had ever been prescribed a GLP-1RA and 760 (5.4%) had ever received liraglutide.

Conclusions: In a cohort of English general practice patients, one in six people with type 2 diabetes met the LEADER inclusion criteria, and less than one in 10 of these received liraglutide, a drug which has demonstrated CV benefits amongst others. There is scope to improve the outlook in people with type 2 diabetes and high CV risk through evidence-based use of specific GLP-1RAs.

Keywords: cardiovascular disease; incretin therapy; liraglutide; primary care; type 2 diabetes.

Conflict of interest statement

M.F. receives financial support for research, speaker meetings and consultancy from AMGEN, MSD, Merck, AstraZeneca, Pfizer, Novo Nordisk Ltd, Eli Lilly and Co. and Sanofi‐Aventis. W.H. receives research funding from Eli Lilly and Co., Novo Nordisk Ltd and AstraZeneca UK Ltd. N.M. has received financial support for research, speaker meetings and consultancy from MSD, Merck, BMS, AstraZeneca, Pfizer, Novo Nordisk Ltd, Eli Lilly and Co. and Sanofi‐Aventis. M.W. is an employee of Novo Nordisk Ltd. S.d.L. receives research funding via the University of Surrey from Eli Lilly Co., GlaxoSmithKline, Takeda, AstraZeneca and Novo Nordisk Ltd.

© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

References

    1. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356:2457‐2471.
    1. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER) . Guidance for industry‐diabetes mellitus — evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 Diabetes. 2008. . Accessed June 12, 2018.
    1. Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369:1317‐1326.
    1. White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369:1327‐1335.
    1. Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;373:232‐242.
    1. Pfeffer MA, Claggett B, Diaz R, et al. ELIXA Investigators. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373:2247‐2257.
    1. Holman RR, Bethel MA, Mentz RJ, et al. EXSCEL Study Group. Effects of once‐weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2017;377:1228‐1239.
    1. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644‐657.
    1. Marso SP, McGuire DK, Zinman B, et al. DEVOTE Study Group. Efficacy and safety of degludec versus glargine in type 2 diabetes. N Engl J Med. 2017;377:723‐732.
    1. Holman RR, Coleman RL, Chan JCN, et al. Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double‐blind, placebo‐controlled trial. Lancet Diabetes Endocrinol. 2017;5:877‐886.
    1. Origin Trial Investigators , Gerstein HC, Bosch J, Dagenais GR, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012;367:319‐328.
    1. Boehringer Ingelheim . Boehringer Ingelheim and Lilly announce Trajenta®‘s CARMELINA® cardiovascular outcome trial met its primary endpoint. 2018. . Accessed December 7, 2018.
    1. Intarcia Therapeutics Inc . Intarcia announces successful cardiovascular safety results in phase 3 FREEDOM‐CVO Trial for ITCA 650, an investigational therapy for type 2 diabetes. 2016. . Accessed December 7, 2018.
    1. Zinman B, Wanner C, Lachin JM, et al. EMPA‐REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117‐2128.
    1. Marso SP, Bain SC, Consoli A, et al. SUSTAIN‐6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834‐1844.
    1. Marso SP, Daniels GH, Brown‐Frandsen K, et al. LEADER Steering Committee., LEADER Tria lnvestigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311‐322.
    1. Wiviott SD, Raz I, Bonaca MP, et al. DECLARE–TIMI 58 Investigators. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380:347‐357.
    1. Hernandez AF, Green JB, Janmohamed S, et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double‐blind, randomised placebo‐controlled trial. Lancet. 2018;392:1519‐1529.
    1. Eli Lilly and Company . Trulicity®(dulaglutide) demonstrates superiority in reduction of cardiovascular events for broad range of people with type 2 diabetes. 2018. . Accessed November 21, 2018.
    1. de Lusignan S, Crawford L, Munro N. Creating and using real‐world evidence to answer questions about clinical effectiveness. J Innov Health Inform. 2015;22:368‐373.
    1. de Lusignan S, Correa A, Smith GE, et al. RCGP Research and Surveillance Centre: 50 years' surveillance of influenza, infections, and respiratory conditions. Br J Gen Pract. 2017;67:440‐441.
    1. Correa A, Hinton W, McGovern A, et al. Royal College of General Practitioners Research and Surveillance Centre (RCGP RSC) sentinel network: a cohort profile. BMJ Open. 2016;6:e011092.
    1. Hinton W, McGovern A, Coyle R, et al. Incidence and prevalence of cardiovascular disease in English primary care: a cross‐sectional and follow‐up study of the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). BMJ Open. 2018;8:e020282.
    1. Hinton W, Feher M, Munro N, de Lusignan S. Does real world use of liraglutide match its use in the LEADER cardiovascular outcome trial? Study protocol. Diabetes Ther. 2018;9:1397‐1402.
    1. McGovern A, Hinton W, Correa A, Munro N, Whyte M, de Lusignan S. Real‐world evidence studies into treatment adherence, thresholds for intervention and disparities in treatment in people with type 2 diabetes in the UK. BMJ Open. 2016;6:e012801.
    1. de Lusignan S. Codes, classifications, terminologies and nomenclatures: definition, development and application in practice. Inform Prim Care. 2005;13:65‐70.
    1. Heath Research Authority . Is my study research? 2017. . Accessed December 14, 2018.
    1. Chan T, Di Iorio CT, de Lusignan S, Lo Russo D, Kuziemsky C, Liaw S‐T. UKNational Data Guardian for Health and Care's Review of Data Security: trust, better security and opt‐outs. J Innov Health Inform. 2016;23:627‐632.
    1. Marso SP, Poulter NR, Nissen SE, et al. Design of the liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) trial. Am Heart J. 2013;166:823‐830.e5.
    1. Chaplin S. Management of diabetic neuropathy: the ADA's latest statement fleshes out NICE guidance. Pract Diabetes. 2017;34:30‐33.
    1. National Institute for Health and care Excellence . Type 2 diabetes in adults: management. 2015. . Accessed June 12, 2018.
    1. National Institute for Health and Care Excellence . Type 2 diabetes in adults: management. 2015. . Accessed December 7, 2018.
    1. American Diabetes Association . 8. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes‐2018. Diabetes Care. 2018;41:S73‐S85.
    1. Scottish Intercollegiate Guidelines Network. Pharmacological management of glycaemic control in people with type 2 diabetes. 2017. . Accessed June 12, 2018.
    1. Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41:2669‐2701.
    1. van Bloemendaal L, IJzerman RG, Ten Kulve JS, et al. GLP‐1 receptor activation modulates appetite‐ and reward‐related brain areas in humans. Diabetes. 2014;63:4186‐4196.
    1. Davies MJ, Bergenstal R, Bode B, et al. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: the SCALE diabetes randomized clinical trial. JAMA. 2015;314:687‐699.
    1. Pi‐Sunyer X, Astrup A, Fujioka K, et al. SCALE Obesity and Prediabetes NN8022‐1839 Study Group. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015;373:11‐22.
    1. le Roux CW, Astrup A, Fujioka K, et al. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double‐blind trial. Lancet. 2017;389:1399‐1409.
    1. McGurnaghan S, Blackbourn LAK, Mocevic E, et al. Cardiovascular disease prevalence and risk factor prevalence in type 2 diabetes: a contemporary analysis. Diabet Med. 2018. 10.1111/dme.13825 Epub ahead of print.
    1. Arnold SV, Inzucchi SE, Tang F, et al. Real‐world use and modeled impact of glucose‐lowering therapies evaluated in recent cardiovascular outcomes trials: an NCDR(R) Research to Practice project. Eur J Prev Cardiol. 2017;24:1637‐1645.
    1. McGovern A, Feher M, Munro N, de Lusignan S. Sodium‐glucose co‐transporter 2 (SGLT2) inhibitor: comparing trial data and real‐world use. Diabetes Ther. 2017;8:365‐376.
    1. Pathirannehelage S, Kumarapeli P, Byford R, Yonova I, Ferreira F, de Lusignan S. Uptake of a dashboard designed to give Realtime feedback to a sentinel network about key data required for influenza vaccine effectiveness studies. Stud Health Technol Inform. 2018;247:161‐165.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe