Lack of response to tirzepatide followed by response to semaglutide in people with moderate obesity

A 40-year-old man with class 2 obesity and elevated insulin resistance lost 20% of his weight after switching from tirzepatide to semaglutide.

• Minimal weight loss (<5%) was observed with tirzepatide despite dose escalation to 15 mg weekly over 6 months.
• Significant weight loss (20%) and normalization of fasting glucose occurred with semaglutide at a dose of 2.4 mg weekly over 6 months.
• Insulin resistance, measured by HOMA-IR, was elevated at 5.0, which may be associated with poor response to tirzepatide.
• The case suggests that individuals with class 2 obesity and insulin resistance may respond differently to weight management medications.
• Persistent increased appetite during tirzepatide treatment could indicate a lack of response, highlighting the need for early assessment.
• Nonresponse to tirzepatide does not exclude the possibility of a positive response to semaglutide.

Simplified