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

Abstract

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. 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. 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). 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. Supported by the Italian Diabetes Society (Società Italiana di Diabetologia).