A 72-year-old woman who couldn't tolerate semaglutide dose escalation due to severe GI side effects experienced significant improvement after adding mirtazapine, enabling successful continued GLP-1 therapy.
Successful dose escalation achievedAfter adding mirtazapine, a 72-year-old patient who couldn't tolerate semaglutide due to severe GI symptoms was able to continue and advance her therapy
What the researchers found
A 72-year-old woman with cognitive impairment, type 2 diabetes, atrial fibrillation, obesity, and mood disorders was unable to escalate her semaglutide dose due to severe nausea, vomiting, and diarrhea. After initiating mirtazapine:
- Gastrointestinal tolerance improved significantly
- Semaglutide therapy was continued with successful dose advancement
- Additional benefits included enhanced mood, better sleep, and improved overall well-being
- No adverse effects related to mirtazapine were observed
The case suggests mirtazapine may serve as an adjunct therapy to improve GLP-1 RA tolerability and adherence.
Why it matters
GI side effects are the most common reason patients discontinue or fail to dose-escalate GLP-1 drugs. Finding effective strategies to manage these side effects could help millions of patients stay on their medication and reach therapeutic doses. Mirtazapine is inexpensive, widely available, and has known anti-emetic properties through 5-HT3 receptor blockade, making it a practical option.
How the study worked
This is a single-patient case report documenting the clinical course of a 72-year-old woman treated with semaglutide who developed limiting gastrointestinal side effects. Mirtazapine was added to manage these symptoms, and the clinical response was observed and reported.
What this study cannot tell us
This is a single case report and cannot establish causation, efficacy, or safety in a broader population. The patient had multiple comorbidities and was taking other medications, making it difficult to isolate mirtazapine's contribution. Mirtazapine can cause weight gain, which could counteract GLP-1 drug benefits in some patients. Randomized controlled trials are needed to validate this approach.
How to read the evidence
This is a single case report — the lowest level of clinical evidence. While it provides a useful clinical observation, it cannot establish whether mirtazapine would work for other patients or whether the improvement was truly due to the medication.
When this study was published
Published in 2025, this case report addresses a very current clinical challenge as GLP-1 prescriptions surge globally.
The bigger picture
As GLP-1 receptor agonists are prescribed to an increasingly diverse patient population — including older adults with multiple comorbidities — managing side effects becomes critical. This case highlights the potential for repurposing existing medications to improve GLP-1 drug tolerance, and adds mirtazapine to the toolkit alongside other anti-emetic strategies.
Questions still open
- Does mirtazapine's anti-nausea effect work through the same 5-HT3 receptor blockade that makes ondansetron effective for GLP-1 side effects?
- Could mirtazapine's weight-gain tendency offset the weight loss benefits of GLP-1 drugs in obesity patients?
- Is mirtazapine more effective than standard anti-emetics for managing GLP-1 receptor agonist-induced GI symptoms?
Common questions
Why does semaglutide cause nausea?
How might mirtazapine help with GLP-1 drug side effects?
Read the original research
Mirtazapine for gastrointestinal side effects of glucagon-like peptide-1 receptor agonist therapy in older adults.
Endocrine regulations, 59(1), 260-264
Citation
Khan, Ali R; Makhoul, Gennifer Wahbah; Raji, Mukaila A. (2025). Mirtazapine for gastrointestinal side effects of glucagon-like peptide-1 receptor agonist therapy in older adults.. Endocrine regulations, 59(1), 260-264. https://doi.org/10.2478/enr-2025-0030