Tirzepatide can help people with obesity lose weight, but the weight loss often includes loss of muscle and bone. Adding plenty of protein and doing regular resistance (strength) training can protect muscle and bone while you’re on the drug. Be careful using it in kids, teens, or older adults because long‑term safety isn’t known, and don’t use it only for short, small‑weight drops as you might regain fat quickly.

To identify patients who may or may not benefit from use of new drugs for weight loss and to aid in minimizing loss of lean mass through proactive nutrition and exercise interventions. Choices and interventions are evaluated using the Grading of Recommendations Assessment, Development and Evaluation framework. Quality varies widely and is documented in multiple tables. Semaglutide and tirzepatide should be used in patients living with obesity or with overweight accompanied by weight-related comorbidity. Long-term use may be necessary. Use in children and adolescents has proven effective for weight reduction, but long-term consequences are unknown. Use in elderly patients may be harmful. Because weight loss by any means is accompanied by loss of lean mass, specifically muscle and bone, particular attention must be paid to nutrition and exercise. Protein supplementation is effective to preserve muscle mass. Resistance training is effective in mitigation of both muscle and bone loss. Both resistance and aerobic training are beneficial in preventing osteopenia in weight loss, which may contribute to premature mortality. There is observational evidence that weight cycling may be harmful in that weight regain can be composed primarily of fat, multiple cycles of which may actually increase obesity in individuals. This is of particular concern because of the cost and limited availability of new weight loss drugs leading to large rates of discontinuation. Similarly, patients using drugs for small amounts of weight loss are likely to regain or overshoot if they discontinue. Patient selection for use of new anti-obesity drugs should match those included in clinical trials and be paired with dietary and exercise interventions used in those trials. Use at the extremes of age is problematic because of lack of long-term data. Intermittent use for small amounts of weight loss may be harmful. More ongoing data are needed.