Treatment Durability

More than 13% of semaglutide users and 9% of tirzepatide users in cited trials were non-responders. Responses to NuSH-based therapies vary substantially. Treatment initiation, adjustment, and discontinuation will be recorded during follow-up. Ghrelin signaling is proposed as a mechanism that may drive increased hunger and appetite following weight loss. Fasting or ketone-producing approaches may reduce the perceived impact of weight regain and hunger signaling. After semaglutide cessation, about 44% of patients regained at least 25% of lost weight within 1 year. About 47%–65% of people with overweight or obesity discontinue GLP-1 receptor agonist therapy. People who lose weight through dieting may later regain more weight than they originally lost. HARMONY examines uncertainties around low-dose GLP-1 receptor agonist use, flexible titration, reinitiation, and sustained weight control.