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Durability of glycaemic control in patients with type 2 diabetes after metformin failure: Prognostic model derivation and validation using the DISCOVER study
Author(s) -
Ling Suping,
Sun Ping,
Zaccardi Francesco,
Khosla Sajan,
Cooper Andrew,
Fenici Peter,
Khunti Kamlesh
Publication year - 2020
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13966
Subject(s) - medicine , logistic regression , type 2 diabetes , observational study , metformin , diabetes mellitus , accelerated failure time model , proportional hazards model , insulin , endocrinology
Abstract Aim To develop and internally validate prognostic models on the long‐term durability of glycaemic control in patients with type 2 diabetes after metformin failure. Materials and Methods DISCOVER is a 3‐year, prospective observational study across six continents investigating second‐line glucose‐lowering therapies. In this analysis from 35 countries, we included patients on metformin initiating second‐line glucose‐lowering medication(s) because of physician‐defined lack of efficacy. The outcome was durability of glycaemic control, defined as three consecutive levels of HbA1c at 6‐, 12‐ and 24‐month follow‐up at target (HbA1c equal to or lower than the level when the physician initiated the second‐line therapy in patients with baseline HbA1c ≤7% [53 mmol/mol]; and equal to or lower than 7% in those with baseline HbA1c >7%). We developed and internally validated two prognostic models: a base model, which included age, sex, ethnicity, country income group, baseline HbA1c and second‐line therapy, and an advanced model, established through statistical variable selections from a model including base variables and 13 additional predictors selected from a literature review. We used logistic regression to develop and 500 bootstrapping samples to internally validate the models; discrimination and calibration were used to assess model performance. Results Overall, 896 out of 2995 participants (29.9%) had sustained glycaemic control. The base model performed well: Nagelkerke R 2 was 0.13, C‐index 0.70 (95% CI: 0.68, 0.71) and bias‐corrected C‐index 0.69 after internal validation. Diabetes duration, insurance type, estimated glomerular filtration rate and glucose self‐monitoring were additionally selected in the advanced model, which had only a slightly better performance compared with the base model: Nagelkerke R 2 0.20, C‐index 0.71 (95% CI: 0.69, 0.73) and bias‐corrected C‐index 0.70. Calibration plots showed good calibrations of both validated models. Conclusion These prognostic models, which include simple demographic and routinely collected clinical information, enabled the estimation of the probability of 2‐year sustained glycaemic control in patients after metformin failure. The models have been implemented into a web‐based tool to support healthcare professionals in their decisions.