In a 36‑week trial with adults who have type 2 diabetes, the experimental peptide retatrutide (especially at 8 mg and 12 mg weekly doses) made participants feel less hungry, less likely to overeat, and more able to control their eating. These appetite changes were linked to bigger drops in body weight, and the effects were generally stronger than those seen with the existing drug dulaglutide.

To determine whether adults with type 2 diabetes (T2D) treated with retatrutide report greater changes in self-reported appetite, dietary restraint, and disinhibition compared to placebo or dulaglutide and to examine associations with weight change. These pre-specified exploratory analyses examined changes from baseline in Appetite Visual Analogue Scale (VAS) and Eating Inventory (EI) scores after 24 and 36 weeks of once-weekly treatment with placebo, dulaglutide 1.5 mg, or retatrutide 0.5, 4, 8, or 12 mg in 275 adults with T2D. Changes from baseline with retatrutide were compared to those with placebo and dulaglutide. Post-hoc correlations between changes in body weight and Appetite VAS/EI scores were also examined. Compared with placebo, participants who received retatrutide ≥4 mg reported greater reductions from baseline in overall appetite, hunger, and prospective food consumption (l at Week 24 (all p <0.05)). Differences versus dulaglutide were less consistent. Improvements from baseline versus placebo in EI Perceived Hunger and Disinhibition were greater in participants who received retatrutide 8 and 12 mg at Weeks 24 and 36. Dietary Restraint increased from baseline versus placebo only in participants who received retatrutide 12 mg at Week 36 (all p <0.05). Reductions in Perceived Hunger and Disinhibition, and increases in Dietary Restraint were significantly correlated with reductions in body weight at Week 36 (r = 0.28, r = 0.36, and r = 0.31, respectively). Perceived hunger and tendency to overeat (disinhibition) were reduced with higher doses of retatrutide, compared with placebo. Greater weight reduction was associated with decreased perceived hunger and disinhibition and increased dietary restraint. WHAT IS THE CONTEXT AND PURPOSE OF THIS RESEARCH STUDY?: Retatrutide is a new treatment currently being developed for people with obesity and people with type 2 diabetes. This study compared the changes in appetite and eating behaviours of adults with T2D who were treated with retatrutide, dulaglutide (an alternative treatment), or placebo (i.e., no treatment). We examined changes in feelings of hunger, satisfaction and fullness, the desire to eat certain types of foods (e.g., sweet, salty or fatty foods), the tendency to overeat (e.g., when stressed), and conscious efforts to limit food intake. We also examined the potential link between changes in appetite or eating behaviours and changes in weight during retatrutide treatment. WHAT WAS DONE?: Adults with type 2 diabetes who participated in this trial completed two questionnaires that measured their eating habits at several time points during the 36-week period in which they received treatment. The questionnaire responses of people who received retatrutide each week (1-4 different doses) were compared with the responses of people who received no treatment (i.e., placebo) and of people who received dulaglutide treatment. Any potential links between the amount of weight reduction people experienced while receiving treatment during the study and their questionnaire responses were also examined. WHAT WERE THE MAIN RESULTS?: This study showed that adults with type 2 diabetes who received higher doses of retatrutide reported being less likely to feel hungry or overeat compared to those who received no treatment (i.e., placebo) or those who received dulaglutide. On average, people who experienced greater weight reduction also reported being less hungry and less likely to overeat. WHAT IS THE ORIGINALITY AND RELEVANCE OF THIS STUDY?: This is the first study to assess changes in appetite and eating behaviours of adults with type 2 diabetes who received retatrutide. Our results suggest that enhanced modification of eating behaviours with retatrutide may assist with weight reduction in adults with type 2 diabetes.