Development of a treatment selection algorithm for SGLT2 and DPP-4 inhibitor therapies in people with type 2 diabetes: a retrospective cohort study

dc.contributor.authorDennis, J. M.
dc.contributor.authorYoung, K. G.
dc.contributor.authorMcGovern, A. P.
dc.contributor.authorMateen, B. A.
dc.contributor.authorVollmer, S. J.
dc.contributor.authorSimpson, M. D.
dc.contributor.authorHenley, W. E.
dc.contributor.authorHolman, R. R.
dc.contributor.authorSattar, N.
dc.contributor.authorPearson, E. R.
dc.contributor.authorHattersley, A. T.
dc.contributor.authorJones, A. G.
dc.contributor.authorShields, B. M.
dc.description.abstractBACKGROUND: 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.
dc.description.admin-notePublished version, accepted version, submitted version
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dc.identifier.citationLancet Digit Health. 2022 Dec;4(12):e873-e883. doi: 10.1016/S2589-7500(22)00174-1.
dc.identifier.journalThe Lancet. Digital health
dc.rightsCopyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.
dc.subjectMiddle Aged
dc.subject*Diabetes Mellitus, Type 2/drug therapy
dc.subject*Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
dc.subjectHypoglycemic Agents/therapeutic use
dc.subjectRetrospective Studies
dc.subjectSodium-Glucose ransporter 2/therapeutic use
dc.subject*Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
dc.subjectClinical Trials as Topic
dc.titleDevelopment of a treatment selection algorithm for SGLT2 and DPP-4 inhibitor therapies in people with type 2 diabetes: a retrospective cohort study
dc.typeJournal Article