Introduction and Objective: Several disease-modifying immunotherapies in new onset type 1 diabetes (T1D) have demonstrated preservation of C-peptide, but associated effects on glycemic control have been variable across studies. Using continuous glucose monitoring (CGM), we examined how preserved C-peptide influences different aspects of glycemia. Methods: We pooled participant level data from six disease modifying intervention trials in new onset T1D (n=495). C-peptide levels were grouped into four ordered categories (0.2, ≥0.2-0.5, ≥0.5-0.8, and ≥0.8). Associations between C-peptide and CGM outcomes were assessed using linear mixed-effects models with fixed effects for C-peptide level and study and a random effect for participant. Significance was evaluated using likelihood ratio tests and tests for linear trend. Results: From the lowest to highest C-peptide groups, there was a significant increase in time in range (3.9-10.0 mmol/L: from 58.5% to 80.5%; p0.001) and time in tight range (3.9-7.8 mmol/L: from 40.1% to 62.4%; p0.001), while HbA1c decreased, but only modestly (7.4% to 6.9%; p0.001). Additionally, across increasing C-peptide levels there were decreases in coefficient of variation (39% to 32%), time spent at 10.0-13.9 mmol/L (21% to 11 %), and 13.9 mmol/L (14.8% to 2.7%); p0.001 for all. Hypoglycemia exposure was low across C-peptide groups, with time spent between 3.0 and 3.9 mmol/L ranging from 3.7-4.1% and time 3.0 mmol/L from 1.2-2.0% and showed no consistent association with C-peptide level. Conclusion: Preserved beta-cell function in new-onset T1D is associated with clear differences in CGM metrics, including higher time in range, lower glycemic variability, and reduced hyperglycemia, but only modestly lower HbA1c and no difference in hypoglycemia. These findings also show that CGM captures glycemic differences that are not apparent using HbA1c alone, supporting its complementary role in evaluating metabolic outcomes in disease modifying immunotherapy trials. Disclosure A. Lam: Advisory Panel; Ended; Vertex Pharmaceuticals Incorporated. T. Bakhtiyarli: None. A.L. Carr: None. C.K. Boughton: Consultant; Current; CamDiab Ltd. Research Support; Current; Abbott Diabetes, Dexcom, Inc., Ypsomed AG. U. Hannelius: Employee; Current; Diamyd Medical. R. Hovorka: Board Member; Current; CamDiab Ltd. Consultant; Current; Abbott Diabetes. Research Support; Current; Abbott Diabetes, Dexcom, Inc., Ypsomed AG, Novo Nordisk Foundation. Other - Speaker bureau; Ended; Novo Nordisk, Eli Lilly and Company. A.L. Lindqvist: Employee; Current; Diamyd Medical AB. J. Ludvigsson: Research Support; Current; Diamyd Medical. Consultant; Current; Diamyd Medical. P. Taylor: None. C.M. Dayan: Consultant; Current; Sanofi, SAB Biotherapeutics, Inc., Immunocore, Ltd. Consultant; Ended; Vertex Pharmaceuticals Incorporated. Consultant; Current; Quell. Advisory Panel; Current; Amarna, ArgenX, Amgen Inc. J.A. Hedrick: None. P. Senior: Consultant; Ended; Abbott. Consultant; Current; Dexcom, Inc. Consultant; Ended; GlaxoSmithKline plc. Research Support; Current; Eli Lilly and Company. Consultant; Current; Novo Nordisk, Sana Biotechnology Inc., Sanofi, Vertex Pharmaceuticals Incorporated. Consultant; Ended; Ypsomed AG.
LAM et al. (Fri,) studied this question.