Durability of glycaemic control in patients with type 2 diabetes after metformin failure: Prognostic model derivation and validation using the DISCOVER study.

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 R2 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 R2 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.