Projects per year
Abstract
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.
Original language | English |
---|---|
Pages (from-to) | E873-E883 |
Number of pages | 11 |
Journal | The Lancet Digital Health |
Volume | 4 |
Issue number | 12 |
Early online date | 22 Nov 2022 |
DOIs | |
Publication status | Published - Dec 2022 |
ASJC Scopus subject areas
- Decision Sciences (miscellaneous)
- Health Information Management
- Health Informatics
- Medicine (miscellaneous)
Fingerprint
Dive into the research topics of 'Development of a treatment selection algorithm for SGLT2 and DPP-4 inhibitor therapies in people with type 2 diabetes: a retrospective cohort study'. Together they form a unique fingerprint.Projects
- 1 Finished
-
Stratified Medicine in Type 2 Diabetes: Insights from the Study of Drug Response (New Investigator Award)
Pearson, E. (Investigator)
16/02/15 → 15/08/21
Project: Research