Tirzepatide (TZP) promotes significant and clinically meaningful weight loss. In a randomized blinded clinical trial in people with obesity undergoing caloric restriction, we investigated the effect of TZP vs Placebo (PBO) on food intake during ad libitum lunch and dinner, appetite, food preference and craving. In this 18wk phase 1 study, 55 people with obesity, with baseline body weight of 102.8 kg were randomized (1:1) to TZP 15 mg or PBO. Food intake was measured during ad libitum lunch (664 kcal, PBO and 682 kcal, TZP) and dinner (1178 kcal, PBO and 1190 kcal, TZP) at baseline and after 18wk of treatment. We measured appetite during fasting and standardized mixed meal tolerance test (sMMTT) with visual analogue scale (VAS) and retrospective VAS (average ratings over the previous week). Food cravings and preferences were measured with the Food Craving Inventory (FCI) and Food Preference Questionnaire (FPQ) at baseline, 8wk and 18wk. At 18wk, mean body weight loss was 16.7 kg with TZP and 8.3 kg with PBO (p<0.001). TZP significantly decreased food intake from baseline during lunch (-285±42 kcal) and dinner (-631±58 kcal) compared to PBO (60± 42, and -116±58 kcal, respectively). TZP significantly lowered appetite at fasting and at each time point during the sMMTT, resulting in decreased hunger and prospective food consumption and increased fullness. Based on retrospective VAS, appetite changes started at 1wk. TZP significantly decreased food preference scores in 10 of 12 FPQ metrics at 8wk and 18wk compared to PBO. TZP significantly decreased the overall FCI score and the sweets, carbohydrates and starches, and fast-food fats sub scores, but not the high fat and fruit and vegetable sub scores, at 8wk and 18wk, compared to PBO. In conclusion, TZP decreased food intake, appetite and food craving and preference. TZP appears to reduce body weight via reductions in food intake and the drive to eat.


C.K.Martin: Board Member; EHE Health, Wondr Health, Other Relationship; ABGIL, Research Support; Pack Health, Evidation Health, Lilly, WW International, Inc. T.Coskun: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. E.Ravussin: Advisory Panel; Novartis, Research Support; Eli Lilly and Company, Novartis AG. G.Sanchez-delgado: Research Support; Eli Lilly and Company, Novo Nordisk, Abbott, Maastricht instruments, Vyaire Medical, ParvoMedics, Cosmed, Speaker's Bureau; Eli Lilly and Company. H.Nishiyama: None. J.Li: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. S.Urva: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. E.J.Pratt: Employee; Eli Lilly and Company. Z.Milicevic: Employee; Eli Lilly and Company. A.Haupt: Employee; Lilly, Stock/Shareholder; Lilly.


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