Why is the patient not losing weight on Zepbound (tirzepatide) 5mg once weekly?

From the Guidelines

If a patient isn't losing weight on Zepbound 5mg once weekly, consider discontinuing the medication if they have not lost at least 4% of their baseline body weight after 16 weeks, as this is a common criterion for discontinuation of similar anti-obesity medications like liraglutide 3.0 mg 1. However, the specific guidance for Zepbound (tirzepatide) is not directly provided in the given evidence. Given the information available, the approach to managing a patient on anti-obesity medication who is not achieving the desired weight loss is to assess their response after a certain period, typically 12 to 16 weeks, and consider discontinuation or adjustment based on predefined percentage weight loss thresholds. For medications like naltrexone ER/bupropion ER, phentermine/topiramate ER, and liraglutide 3.0 mg, specific criteria are provided for when to discontinue or adjust the medication based on weight loss response 1. Since Zepbound works similarly by affecting appetite and glucose metabolism, it's reasonable to apply a similar principle, although the exact threshold might differ. It's crucial to monitor the patient's weight loss progress, ensure adherence to the medication regimen, and encourage concurrent lifestyle modifications such as diet and exercise to enhance the medication's effectiveness. Additionally, reviewing potential side effects and contraindications, as outlined for semaglutide, another GLP-1 analog 1, can help in managing expectations and safety. Given the lack of direct guidance on Zepbound in the provided evidence, a conservative approach based on the principles guiding the use of similar medications seems prudent. Thus, discontinuation or adjustment should be considered based on clinical judgment and the patient's overall response to the medication, prioritizing their safety and potential for achieving significant weight loss. It's also important to note that the FDA indication for anti-obesity medications, including those like Zepbound, typically involves a BMI of 30 kg/m² or higher, or 27 kg/m² with significant complications, highlighting the need for careful patient selection and monitoring 1.

From the FDA Drug Label

Tirzepatide lowers fasting and postprandial glucose concentration, decreases food intake, and reduces body weight in patients with type 2 diabetes mellitus. The patient is not losing weight on Zepbound 5mg once weekly, which is unexpected as tirzepatide is known to reduce body weight in patients with type 2 diabetes mellitus 2.

• Possible reasons for not losing weight are not explicitly stated in the drug label.
• The drug label does mention that tirzepatide decreases food intake and reduces body weight, but it does not provide information on what to do if a patient is not losing weight while taking the medication.
• Clinical judgment is required to determine the best course of action for this patient.

From the Research

Patient Not Losing Weight on Zepbound 5mg Once Weekly

• The patient's lack of weight loss on Zepbound 5mg once weekly may be due to various factors, including physical activity level and overall lifestyle habits 3, 4, 5.
• Studies have shown that physical activity alone is a poor strategy for weight loss, but it is crucial for weight loss maintenance 3.
• Regular physical activity has multiple beneficial effects on overall health, including reducing the risk of obesity-associated diseases, such as type 2 diabetes and cardiovascular diseases, independently of weight loss and BMI 3, 4.
• The health benefits of physical activity can be achieved with relatively minor volumes of activity, and current threshold-based messaging may create an unnecessary barrier to those who might benefit from becoming more active 4.
• Exercise should be discussed as a serious form of treatment, similar to medication, and should be thoughtfully prescribed to every patient, taking into account their individual needs and risk factors 5.
• In terms of the medication itself, tirzepatide has been shown to provide substantial and sustained reductions in body weight in persons with obesity over a 72-week period, with a mean percent change in body weight of -12.3% with the 5-mg dose 6.
• However, individual results may vary, and factors such as diet, lifestyle, and overall health status may influence the effectiveness of the medication 7, 6.