Weight gain is a well-known side effect of Lorlatinib, and real-world studies suggest it may be even more common than clinical trials initially showed. Now researchers are learning more about where that extra weight goes and what might help prevent it. A recent study looked at CT scans from 67 people with ALK-positive lung cancer taking Lorlatinib. The researchers found that weight gain was associated particularly with an increase in visceral fat, the deeper abdominal fat that surrounds internal organs and is linked to cardiovascular and metabolic risk.
GLP-1 drugs, such as Ozempic, have become popular and effective treatments for diabetes and weight loss. So it’s reasonable to ask: Could they also help reduce the visceral weight gain associated with Lorlatinib?
One patient in the study offered an answer to this question. After gaining 16 kg, about 35 pounds, over three years on Lorlatinib, the patient started dulaglutide, a GLP-1 medication also known as Trulicity. Both BMI and visceral fat subsequently decreased. Of course, one patient can’t tell us whether GLP-1 drugs will work broadly for Lorlatinib-related weight gain.
Now researchers are going to test the idea. A new University of Chicago clinical trial, NCT07782359, will study tirzepatide, a GIP/GLP-1 medication known as Zepbound, in people with advanced ALK-positive lung cancer receiving first-line Lorlatinib. The phase 1 study plans to enroll 30 patients and will look at whether tirzepatide can help control Lorlatinib-associated weight gain and metabolic changes.
The trial is not yet recruiting, but it is an interesting example of research aimed not at fighting the cancer itself, but at making an effective ALK treatment easier and healthier to live with in the long run.
References
Clinical trial: NCT07782359 on ClinicalTrials.gov
Visceral fat study: Weight Gain on Lorlatinib Is Associated With Accumulation of Visceral Adipose Tissue, Journal of Thoracic Oncology, 2026. https://pubmed.ncbi.nlm.nih.gov/42419484/
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Author: Ellee Urban
