| アブストラクト | BACKGROUND: Current treatment guidelines do not provide recommendations to support the selection of treatment for most people with type 2 diabetes. We aimed to develop and validate an algorithm to allow selection of optimal treatment based on glycaemic response, weight change, and tolerability outcomes when choosing between SGLT2 inhibitor or DPP-4 inhibitor therapies. METHODS: In this retrospective cohort study, we identified patients initiating SGLT2 and DPP-4 inhibitor therapies after Jan 1, 2013, from the UK Clinical Practice Research Datalink (CPRD). We excluded those who received SGLT2 or DPP-4 inhibitors as first-line treatment or insulin at the same time, had estimated glomerular filtration rate (eGFR) of less than 45 mL/min per 1.73 m(2), or did not have a valid baseline glycated haemoglobin (HbA(1c)) measure (<53 or >/=120 mmol/mol). The primary efficacy outcome was the HbA(1c) value reached 6 months after drug initiation, adjusted for baseline HbA(1c). Clinical features associated with differential HbA(1c) outcome on the two therapies were identified in CPRD (n=26 877), and replicated in reanalysis of 14 clinical trials (n=10 414). An algorithm to predict individual-level differential HbA(1c) outcome on the two therapies was developed in CPRD (derivation; n=14 069) and validated in head-to-head trials (n=2499) and CPRD (independent validation; n=9376). In CPRD, we further explored heterogeneity in 6-month weight change and treatment discontinuation. FINDINGS: Among 10 253 patients initiating SGLT2 inhibitors and 16 624 patients initiating DPP-4 inhibitors in CPRD, baseline HbA(1c), age, BMI, eGFR, and alanine aminotransferase were associated with differential HbA(1c) outcome with SGLT2 inhibitor and DPP-4 inhibitor therapies. The median age of participants was 62.0 years (IQR 55.0-70.0). 10 016 (37.3%) were women and 16 861 (62.7%) were men. An algorithm based on these five features identified a subgroup, representing around four in ten CPRD patients, with a 5 mmol/mol or greater observed benefit with SGLT2 inhibitors in all validation cohorts (CPRD 8.8 mmol/mol [95% CI 7.8-9.8]; CANTATA-D and CANTATA-D2 trials 5.8 mmol/mol [3.9-7.7]; BI1245.20 trial 6.6 mmol/mol [2.2-11.0]). In CPRD, predicted differential HbA(1c) response with SGLT2 inhibitor and DPP-4 inhibitor therapies was not associated with weight change. Overall treatment discontinuation within 6 months was similar in patients predicted to have an HbA(1c) benefit with SGLT2 inhibitors over DPP-4 inhibitors (median 15.2% [13.2-20.3] vs 14.4% [12.9-16.7]). A smaller subgroup predicted to have greater HbA(1c) reduction with DPP-4 inhibitors were twice as likely to discontinue SGLT2 inhibitors than DPP-4 inhibitors (median 26.8% [23.4-31.0] vs 14.8% [12.9-16.8]). INTERPRETATION: A validated treatment selection algorithm for SGLT2 inhibitor and DPP-4 inhibitor therapies can support decisions on optimal treatment for people with type 2 diabetes. FUNDING: BHF-Turing Cardiovascular Data Science Award and the UK Medical Research Council. |
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| ジャーナル名 | The Lancet. Digital health |
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| Pubmed追加日 | 2022/11/26 |
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| 投稿者 | Dennis, John M; Young, Katherine G; McGovern, Andrew P; Mateen, Bilal A; Vollmer, Sebastian J; Simpson, Michael D; Henley, William E; Holman, Rury R; Sattar, Naveed; Pearson, Ewan R; Hattersley, Andrew T; Jones, Angus G; Shields, Beverley M |
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| 組織名 | University of Exeter Medical School, Institute of Biomedical and Clinical;Science, Royal Devon and Exeter Hospital, Exeter, UK. Electronic address:;j.dennis@exeter.ac.uk.;Science, Royal Devon and Exeter Hospital, Exeter, UK.;The Alan Turing Institute, British Library, London, UK; Institute of Health;Informatics, University College London, London, UK.;Department of Statistics, University of Warwick, Coventry, UK.;Newcastle University, Newcastle upon Tyne, UK.;Institute of Health Research, University of Exeter Medical School, Exeter, UK.;Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford,;Churchill Hospital, Oxford, UK.;Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow,;UK.;Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical;School, University of Dundee, Dundee, UK. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/36427949/ |
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