Type 2 diabetes remission after initiation of GLP-1 receptor agonists: frequency, characteristics, and outcomes using multiple definitions in an observational study
Gian Paolo Fadini, Andrea Giaccari, Fabio Broglio, Laura Nollino, Bruno Fattor, Roberto Anichini, Giancarla Meregalli, Angelo Avogaro, Agostino Consoli, Gianluca Aimaretti, Roberto Anichini, Angelo Avogaro, M Baldassarre, Cristina Barale, Rosella Cau, Agostino Consoli, Agostino Consoli, Bruno Fattor, Stefano Fazion, Gloria Formoso, Mariangela Ghiani, Frida Leonetti, Gaetano Leto, Elena Melchionda, Giancarla Meregalli, Andrea Muscarà, Laura Nollino, Agostino Paccagnella, Giuseppina Russo, Marco Strazzabosco, Marco Zavattaro, Marco Strazzabosco, Marco Zavattaro
Abstract
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: , 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).