Weight loss improves glycemia. We performed exploratory analysis of an RCT using the OP (n=135) MRP vs food-based (FB) diet (n=138), that showed significant weight loss at week (W) 26 (reduction phase) and W52 (maintenance), to evaluate potential differential glycemic/weight effects by glycemic status (NG: no type 2 diabetes [T2D], HbA1c < 5.7%, and FPG < 100 mg/dL, or dysglycemia: prediabetes or T2D). We assessed changes in anthropometrics and glycemia using a linear and logistic (Odds Ratio [OR]) mixed effects model. Baseline (BL) characteristics were similar within the OP/FB subgroups, but the NG (n=134) vs dysglycemia (n=139) group were slightly younger (mean age 44/50 yrs) and had a lower HbA1c (5.4/6.1%). FPG and HbA1c decreased at W26 within both groups (Table), with a differential effect for FPG favoring OP in those with NG. At W52, the pattern was similar, but with smaller reductions. Weight loss was numerically greater with OP vs FB in those with dysglycemia vs NG at both W26 and W52; ORweight loss ≥10% W26: 5.80 (2.62, 12.86), p<0.0001 vs NG: 3.36 (1.58, 7.15), p=0.002; ORweight loss ≥10% W52: 4.26 (1.85, 9.83), p=0.001 vs NG: 2.08 (0.97, 4.47), p=0.06). Although both groups significantly lost weight, those with dysglycemia at BL had greater weight loss and the higher protein content in the OP MRP may play a role. Disclosure A.E.Rothberg: None. J.D.Ard: Advisory Panel; Novo Nordisk, Consultant; Eli Lilly and Company, Intuitive Surgical, Regeneron, Other Relationship; Optum Labs, Weight Watchers International, Research Support; Nestlé Health Science, Boehringer Ingelheim Inc., Epitomee, KVK Tech. M.Dar: None. J.Loper: Advisory Panel; Nestlé Health Science. A.H.Hawkinson: Employee; Nestlé Health Science. S.S.Cohen: Consultant; Nestlé Health Science. O.Johansen: Employee; Nestlé Health Science. Funding Nestlé Health Science