How would you manage a patient taking a GLP-1 agonist for weight loss who continues to have symptoms (i.e., nausea, vomiting) related to reduced GI motility despite dose adjustments?

Anecdotally, I’ve had good success using prucalopride at twice-daily dosing (0.5 mg BID or 1 mg BID) in select patients. In my experience, tirzepatide tends to be better tolerated than semaglutide from a gastrointestinal perspective.

First, it is important not to assume the symptoms are arising from dysmotility. Research from Camilleri & Sanders, PMID 34717924 at the Mayo Clinic, has identified that there is tachyphlyaxis to the delayed gastric emptying- that is to say that this normalizes in most patients. Next, since constipat...

A couple of things I’ve noticed with GLP-1:

• Tirzepatide seems to be tolerated better
• get them on fiber supplementation and treat any underlying GERD or constipation
• make sure they aren’t overeating on their injection day

I would use the minimal dose that is able to achieve weight loss with minimal to no side effects. Otherwise, I would shift to an alternative drug.

Titrate dose upward very slowly to allow AE’s to diminish. No hurry to get to the effective dose for weight loss, as this is a long-term therapy…