Type 2 diabetes remission after initiation of GLP-1 receptor agonists: frequency, characteristics, and outcomes using multiple definitions in an observational study

Background: Remission of type 2 diabetes (T2D) is becoming feasible with modern treatments, including GLP-1 receptor agonists (GLP-1RA). Here, we explored frequency, characteristics, and outcomes associated with various definitions of remission after initiation of GLP-1RA. Methods: This was an observational study on new-users of GLP-1RA. We explored 4 definitions of remission: (1) HbA1c to <6.5% persisting ≥3 months in the absence of diabetes pharmacotherapy; (2) As in 1, but allowing GLP-1RA therapy; (3) As in 1, but without new diabetes pharmacotherapy; (4) As in 1, but irrespectively of ongoing diabetes pharmacotherapy. Findings: We included 14,141 participants initiating GLP-1RA (60% men, 60-year-old, with a diabetes duration of ∼10 years, BMI 32 kg/m2, HbA1c 8.1%). The mean observation was 4 years. Remission frequencies by definition were: (1) 5.8%; (2) 6.2%; (3) 12.2%; (4) 18.3%. Duration was shorter for remission 1–2 (5–6 months) than for remission 3–4 (9–10 months). Factors associated with remission were similar across definitions (shorter diabetes duration, higher BMI, lower burden of complications and medications). Remission was associated with significant and sustained benefits on HbA1c (–1%) and body weight (–2 kg). Microvascular events were reduced by 12–16% in participants with remission 1, 2 or 3. Cardiovascular events were reduced only in remission 3 (HR 0.65; 95% C.I. 0.48–0.88). Interpretation: T2D remission is not rare after initiation GLP-1RA, its frequency and duration varying by definition. When achieved, remission is associated with durable metabolic improvements up to 4 years and fewer incident complications. Funding: Supported by the Italian Diabetes Society (Società Italiana di Diabetologia).