Predicting post one-year durability of glucose-lowering monotherapies in patients with newly-diagnosed type 2 diabetes mellitus – A MASTERMIND precision medicine approach (UKPDS 87). (August 2020)

• Record Type: Journal Article
• Authors: Agbaje, Olorunsola F.; Coleman, Ruth L.; Hattersley, Andrew T.; Jones, Angus G.; Pearson, Ewan R.; Shields, Beverley M.; Holman, Rury R.
• Is Part Of: Diabetes research and clinical practice. Volume 166(2020)
• Publication Date: 2020-08
• Subjects: Precision medicine -- Modelling -- Durability -- Glucose-lowering agents -- Monotherapy failure; AFT Accelerated failure time -- CC Complete case -- eGFR Estimated glomerular filtration rate -- FPG Fasting plasma glucose -- MDRD Modification of Diet in Renal Disease -- MICD Multiply-imputed complete data -- T2D Type 2 diabetes mellitus -- UKPDS UK Prospective Diabetes Study; Diabetes -- Periodicals; Diabetes Mellitus -- Periodicals; 616.462
• DOI: 10.1016/j.diabres.2020.108333
• Languages: English
• ISSNs: 0168-8227

Abstract

Abstract: Aims: Predicting likely durability of glucose-lowering therapies for people with type 2 diabetes (T2D) could help inform individualised therapeutic choices. Methods: We used data from UKPDS patients with newly-diagnosed T2D randomised to first-line glucose-lowering monotherapy with chlorpropamide–glibenclamide–basal insulin or metformin. In 2339 participants who achieved one-year HbA1c values <7.5% (<59 mmol/mol)–we assessed relationships between one-year characteristics and time to monotherapy-failure (HbA1c ≥ 7.5% or requiring second-line therapy). Model validation was performed using bootstrap sampling. Results: Follow-up was median (IQR) 11.0 (8.0–14.0) years. Monotherapy-failure occurred in 72%–82%–75% and 79% for those randomised to chlorpropamide–glibenclamide–basal insulin or metformin respectively–after median 4.5 (3.0–6.6)–3.7 (2.6–5.6)–4.2 (2.7–6.5) and 3.8 (2.6– 5.2) years. Time-to-monotherapy-failure was predicted primarily by HbA1c and BMI values–with other risk factors varying by type of monotherapy–with predictions to within ±2.5 years for 55%–60%–56% and 57% of the chlorpropamide–glibenclamide–basal insulin and metformin monotherapy cohorts respectively. Conclusions: Post one-year glycaemic durability can be predicted robustly in individuals with newly-diagnosed T2D who achieve HbA1c values < 7.5% one year after commencing traditional monotherapies. Such information could be used to help guide glycaemic management for individual patients.