AIMS:To inform patients and their carers about both the probability of reducing glycated haemoglobin (HbA1c) to clinically desirable levels and the sustainability of such control over 2 years with major second-line antidiabetic therapies, in individual risk scenarios, with and without third-line intensification. MATERIALS AND METHODS:From US Centricity Electronic Medical Records, 163 081 patients with type 2 diabetes aged 18 to 80 years, who had initiated metformin, intensified their treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs), sulphonylureas (SUs), insulin or thiazolidinediones (TZDs), and continued second-line treatment for ≥6 months, were selected. Treatment groups were balanced with regard to baseline characteristics, and glycaemic achievements were estimated using logistic regression analysis. RESULTS:With HbA1c concentrations of 58-63.9 mmol/mol (7.5-7.9%) at second-line treatment initiation, the adjusted probabilities of achieving HbA1c <53 mmol/mol (<7%) at 6 months were 32%, 38%, 39%, 26% and 38% in the SU, DPP-4 inhibitor, GLP-1RA, insulin and TZD groups, respectively, while with baseline HbA1c concentrations of 64-75 mmol/mol (8-9%), the corresponding probabilities of reducing HbA1c to <58 mmol/mol (<7.5%) were 38%, 44%, 40%, 34% and 42%, respectively. In these baseline HbA1c categories, the adjusted probabilities of sustaining HbA1c achievements over 2 years were higher in the GLP-1RA and TZD groups, compared with the SU and insulin groups (P < .01). With baseline HbA1c concentrations of 75.1-108 mmol/mol (9.1-12%) 38% of patients achieved an HbA1c concentration <58 mmol/mol (<7.5%) at 6 months. The adjusted probability of sustaining this control over 2 years was higher in the incretin and TZD groups (range 62%-75%), while insulin and SUs offered lower chances of sustainable control (range 54%-56%). CONCLUSIONS:Patients treated with second-line incretins and TZDs had a significantly higher probability of achieving and sustaining glycaemic control over 2 years without further intensification, compared with those treated with SUs or insulin.