Aims: To identify subgroups of patients with type 2 diabetes mellitus (T2DM) following distinct trajectories of HbA1c after insulin initiation and explore underlying differences in clinical characteristics. Materials and methods: A cohort study was conducted in patients with T2DM initiating insulin in 2007–2013 with a follow-up of 2 to 4 years. Data were collected from the Groningen Initiative to Analyze Type 2 Diabetes Treatment (GIANTT) database. The primary outcome was subgroups with different trajectories of HbA1c patterns after insulin initiation, as identified by latent class growth modeling. Differences between subgroups were tested using one-way ANOVA, Kruskal-Wallis or chi-square tests, where appropriate. Results: From 1459 patients, three subgroups with distinct HbA1c patterns were identified. Group 1 (8%) initially showed a moderate decrease followed by an increase in HbA1c 2 years later, despite receiving more comedication. Group 2 (84%) showed a stable decrease. Group 3 (8%) had a high initial level of HbA1c and a rapid decline within the first year, followed by a slow increase thereafter. Group 1 patients were on average 6–7 years younger than patients in groups 2 and 3 and were more likely to receive sulfonylureas than Group 3 patients. Group 3 patients had a shorter diabetes duration and were less well-controlled for HbA1c, systolic blood pressure and LDL-cholesterol at insulin initiation. Conclusions: Most patients showed a stable HbA1c response, but one out of six patients showed either a poor response, or a rapid initial response only after insulin initiation. Response patterns were associated with age, diabetes duration and risk-factor controls at the time of insulin initiation.