TY - JOUR
T1 - Patient preference for second- and third-line therapies in type 2 diabetes
T2 - a prespecified secondary endpoint of the TriMaster study
AU - Shields, Beverley M.
AU - Angwin, Catherine D.
AU - Shepherd, Maggie H.
AU - Britten, Nicky
AU - Jones, Angus G.
AU - Sattar, Naveed
AU - Holman, Rury
AU - Pearson, Ewan R.
AU - Hattersley, Andrew T.
N1 - Funding Information:
NS is supported by a BHF Centre of Excellence Award (RE/18/6/34217). RH is an Emeritus National Institute for Health Research Senior Investigator. AH was a Wellcome Senior Investigator (098395/Z/12/Z) and is an emeritus Senior Investigator at the NIHR. AH, BS, MS, AG and CA are supported by the NIHR Exeter Clinical Research Facility and National Institute for Health and Care Research Exeter Biomedical Research Centre. EP has received Honoraria from Lilly, Sanofi and Illumina. NS has consulted for and/or received speaker honoraria from Abbott Laboratories, Afimmune, Amgen, Astrazeneca, Boehringer Ingelheim, Eli-Lilly, Hanmi Pharmaceuticals, Janssen, MSD, Novo Nordisk, Novartis, Sanofi and Pfizer and received grant funding paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis and Roche Diagnostics. RRH reports research support from AstraZeneca, Bayer and Merck Sharp & Dohme, and personal fees from Anji Pharmaceuticals, AstraZeneca, Novartis and Novo Nordisk. The remaining authors declare no competing interests.
This trial is part of the MASTERMIND (MRC APBI Stratification and Extreme Response Mechanism IN Diabetes) consortium and is supported by the UK Medical Research Council study grant number MR/N00633X/1. The TriMaster trial was supported by the National Institute for Health and Care Research Exeter Biomedical Research Centre and National Institute for Health and Care Research Exeter Clinical Research Facility. The funder had no role in study design, data collection, data analysis, data interpretation, decision to publish or preparation of the manuscript. The views expressed are those of the author(s) and not necessarily those of the MRC, the NIHR or the Department of Health and Social Care. For the purpose of open access, the author has applied a ‘Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising.
Copyright:
© 2022, The Author(s) under exclusive license to Springer Nature America, Inc.
PY - 2023/2
Y1 - 2023/2
N2 - Patient preference is very important for medication selection in chronic medical conditions, like type 2 diabetes, where there are many different drugs available. Patient preference balances potential efficacy with potential side effects. As both aspects of drug response can vary markedly between individuals, this decision could be informed by the patient personally experiencing the alternative medications, as occurs in a crossover trial. In the TriMaster (NCT02653209, ISRCTN12039221), randomized double-blind, three-way crossover trial patients received three different second- or third-line once-daily type 2 diabetes glucose-lowering drugs (pioglitazone 30 mg, sitagliptin 100 mg and canagliflozin 100 mg). As part of a prespecified secondary endpoint, we examined patients’ drug preference after they had tried all three drugs. In total, 448 participants were treated with all three drugs which overall showed similar glycemic control (HbA1c on pioglitazone 59.5 sitagliptin 59.9, canagliflozin 60.5 mmol mol−1, P = 0.19). In total, 115 patients (25%) preferred pioglitazone, 158 patients (35%) sitagliptin and 175 patients (38%) canagliflozin. The drug preferred by individual patients was associated with a lower HbA1c (mean: 4.6; 95% CI: 3.9, 5.3) mmol mol−1 lower versus nonpreferred) and fewer side effects (mean: 0.50; 95% CI: 0.35, 0.64) fewer side effects versus nonpreferred). Allocating therapy based on the individually preferred drugs, rather than allocating all patients the overall most preferred drug (canagliflozin), would result in more patients achieving the lowest HbA1c for them (70% versus 30%) and the fewest side effects (67% versus 50%). When precision approaches do not predict a clear optimal therapy for an individual, allowing patients to try potential suitable medications before they choose long-term therapy could be a practical alternative to optimizing treatment for type 2 diabetes.
AB - Patient preference is very important for medication selection in chronic medical conditions, like type 2 diabetes, where there are many different drugs available. Patient preference balances potential efficacy with potential side effects. As both aspects of drug response can vary markedly between individuals, this decision could be informed by the patient personally experiencing the alternative medications, as occurs in a crossover trial. In the TriMaster (NCT02653209, ISRCTN12039221), randomized double-blind, three-way crossover trial patients received three different second- or third-line once-daily type 2 diabetes glucose-lowering drugs (pioglitazone 30 mg, sitagliptin 100 mg and canagliflozin 100 mg). As part of a prespecified secondary endpoint, we examined patients’ drug preference after they had tried all three drugs. In total, 448 participants were treated with all three drugs which overall showed similar glycemic control (HbA1c on pioglitazone 59.5 sitagliptin 59.9, canagliflozin 60.5 mmol mol−1, P = 0.19). In total, 115 patients (25%) preferred pioglitazone, 158 patients (35%) sitagliptin and 175 patients (38%) canagliflozin. The drug preferred by individual patients was associated with a lower HbA1c (mean: 4.6; 95% CI: 3.9, 5.3) mmol mol−1 lower versus nonpreferred) and fewer side effects (mean: 0.50; 95% CI: 0.35, 0.64) fewer side effects versus nonpreferred). Allocating therapy based on the individually preferred drugs, rather than allocating all patients the overall most preferred drug (canagliflozin), would result in more patients achieving the lowest HbA1c for them (70% versus 30%) and the fewest side effects (67% versus 50%). When precision approaches do not predict a clear optimal therapy for an individual, allowing patients to try potential suitable medications before they choose long-term therapy could be a practical alternative to optimizing treatment for type 2 diabetes.
KW - Randomized controlled trials
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85143821845&partnerID=8YFLogxK
U2 - 10.1038/s41591-022-02121-6
DO - 10.1038/s41591-022-02121-6
M3 - Article
C2 - 36477734
SN - 1078-8956
VL - 29
SP - 384
EP - 391
JO - Nature Medicine
JF - Nature Medicine
ER -