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CC BY 4.0 · Ibnosina Journal of Medicine and Biomedical Sciences 2025; 17(03): 133-136
DOI: 10.1055/s-0045-1811649
Clinical Vignette

Balancing Benefit and Risk: Continuing Tirzepatide after Allergic Reactions

Salem A. Beshyah 
1   Department of Medicine, Bareen International Hospital, Abu Dhabi, United Arab Emirates
2   Department of Medicine, College of Medicine, Dubai Medical University, Dubai, United Arab Emirates
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Funding and Sponsorship None.
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Abstract

Background

Tirzepatide is increasingly used for weight management in individuals with obesity. This case report explores the ethical, legal, and clinical considerations involved in continued tirzepatide therapy supported by antihistamine co-treatment after a mild allergic reaction in a patient with severe obesity.

Case Description

A 48-year-old woman with a body mass index of 38 kg/m2 developed a localized erythematous skin reaction at the injection site following dose escalation of tirzepatide, lasting 5 to 6 days after each injection. The reaction persisted despite the use of antihistamines. Motivated by the significant weight loss (12 kg in 6 weeks) and the mild nature of the reaction, a shared decision was made to continue therapy under close monitoring. This was later reconsidered when the benefit of weight loss ceased.

Conclusion

This case illustrates a cautious, ethically grounded approach to individualized therapy continuation following mild allergic reactions.


 

Keywords

obesity - GLP-1 RA therapy - drug allergy - side effects - tirzepatide - ethical practice - medicolegal

Introduction

Obesity is a chronic, relapsing condition associated with substantial morbidity and mortality.[1] For individuals with severe obesity, pharmacologic interventions such as GLP-1 receptor agonists (GLP-1 RAs) and GIP-GLP-1 RAs offer clinically meaningful weight loss and metabolic improvement.[2] However, like all medications, GLP-1 RAs carry risks, including rare but potentially serious hypersensitivity reactions.[3] The public knowledge about these benefits drives out-of-pocket self-medications in many parts of the world.

Clinical guidelines emphasize discontinuation of a medication following allergic reactions, especially those suggestive of IgE-mediated processes or systemic involvement.[4] However, for patients who experience substantial benefit and have limited alternative options, the decision to continue therapy despite a mild reaction presents a clinical and ethical challenge. This is especially relevant in cases where the reaction is nonprogressive and manageable with antihistamines, and the patient is fully informed of the potential risks.[5]

The present case report explores the ethical and clinical implications of continuing GIP-GLP-1 RA therapy in a patient who experienced a skin rash caused by tirzepatide. It emphasizes the importance of individualized care, shared decision-making, and close monitoring while reviewing current guidance on drug hypersensitivity and obesity pharmacotherapy.


 

Case Description

A 48-year-old woman made a self-referral to the endocrine clinic to seek help for weight management, specifically using tirzepatide. Her weight was 101 kg, and her height was 164 cm, corresponding to a body mass index of 38.0 kg/m2. She had transient subclinical hyperthyroidism with a small thyroid nodule TIRADS 1 and negative antithyroid antibodies. She had a history of paroxysmal tachycardia treated with a beta-adrenergic blocker, which kept it under control. She has no other comorbidities and was not receiving any other medications. She has attempted unsupervised dietary changes with limited physical activity. After discussing the pros and cons of using GLP1 RA therapy, it was agreed to start her on tirzepatide in doses rapidly titrated at 2-week intervals from 2.5 mg weekly, increasing quickly to 5, 7.5, and 10 mg weekly.

She experienced significant weight loss of 12 kg in the first 6 weeks. However, from her third dose onwards, she developed a localized, 5 × 10 cm, erythematous, intensely itchy skin rash at the injection site lasting for 5 to 6 days ([Fig. 1]). The nature and severity of the skin reaction were similar at all injection sites, including those on the right and left sides, as well as the abdomen and thigh ([Fig. 2]). However, she experienced no other systemic symptoms. There was no personal or family history of atopy or drug allergy. The nature and severity of the reaction were not affected by the coadministration of antihistamine (fexofenadine 120 mg once daily). The patient was very happy with the magnitude of the weight loss. She was keen to explore ways to continue treatment. The physician and the patient discussed the options and had a shared management plan, which will be elaborated later.

Zoom
Fig. 1 The evolution of the skin reaction on days 1, 2, and 5 of a single injection.
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Fig. 2 A similar type and severity of the reaction occurred in different parts of the body in response to two consecutive injections.

 

Discussion

This clinical vignette presents three clinical and ethical questions ([Box 1]). It is particularly relevant to medications that patients may demand and use without medical supervision.

Box 1

Key ethical and clinical questions

1. What are the clinical, legal, and ethical issues of continuing to use GLP-1 RAs (together with antihistamines to mitigate the effect) in a patient who demonstrated a mild to moderate allergic reaction?

2. What are the common patient populations who benefit from continued use despite mild allergic reactions?

3. What are the long-term safety concerns of combining antihistamines with GLP-1 RAs for weight loss?

GLP-1 RAs: glucagon-like peptide-1 receptor agonists

First, the continued use of a medication after a mild to moderate allergic reaction (such as a skin rash), with adjunctive antihistamines, is sometimes considered when the medication provides significant benefit and alternatives are limited or less effective. This approach is most often reserved for nonsevere, benign, T-cell–mediated cutaneous eruptions without systemic or organ involvement. The American Academy of Allergy, Asthma, and Immunology recommends that, in select cases, “treating through” with antihistamines (and sometimes corticosteroids) may be reasonable, but is not recommended for IgE-mediated reactions (e.g., urticaria, angioedema) or severe T-cell–mediated reactions (e.g., Stevens-Johnson syndrome).[1] [2]

Clinical considerations include careful risk stratification: the reaction must be mild, nonprogressive, and without systemic features. Close monitoring is essential, as progression to more severe reactions (including anaphylaxis) can occur unpredictably. GLP-1 RAs have been reported to carry rare but severe risks of hypersensitivity. Antihistamines (preferably second generation) may be used for symptom control, but do not prevent severe reactions. Systemic corticosteroids are sometimes used in the short term, but long-term use is discouraged due to adverse effects.[3] [4] [5] [6] [7]

Legal and ethical considerations require informed consent, which involves an explicit discussion of the risks, benefits, and alternatives. The patient must understand the potential for escalation to severe reactions and the limitations of antihistamines as adjunctive, not preventive, therapy. Documentation of shared decision-making is critical. This approach is not standard of care and should only be considered when the benefit is substantial and no safer alternatives exist. The principle of beneficence underpins the decision to continue therapy, where significant health gains justify measured risk. However, this must be balanced with justice, ensuring consistent standards across similar cases.[8] In the present case, the patient was very pleased with the response to the tirzepatide therapy; however, she carefully considered the physician's concerns before making her choice.

Second, patients with severe obesity and/or those with obesity-related comorbidities who have failed to achieve or maintain clinically meaningful weight loss with lifestyle interventions and for whom alternative pharmacologic or surgical options are less effective, less acceptable, or contraindicated are most likely to benefit from the continued use of non-essential medications such as GLP-1 RAs despite experiencing mild to moderate allergic reactions like a skin rash, provided that the response is nonsevere, nonprogressive, and can be controlled with antihistamines.[8] [9] [10] The patient demonstrated and perceived a significant benefit from the medication, namely, her long-sought weight reduction, which outweighs the risk of the skin reaction. This approach should be considered only after a thorough risk–benefit assessment, shared decision-making, and documentation of informed consent. Relevant professional associations emphasize that GLP-1 RAs are indicated for patients with obesity or overweight status as stated earlier.[8] [10] They also stress that adverse effects should be managed with clinical judgment, including dose adjustment or discontinuation if reactions are severe or progressive.[8] [10] Patients with a history of severe hypersensitivity reactions or those with alternative therapies are not appropriate candidates for continued use.[3] [4]

Third, the long-term safety concerns associated with the combined use of antihistamines and GLP-1 RAs for weight loss in patients who have experienced mild to moderate allergic reactions, but continue therapy due to significant benefit and lack of alternatives, include the potential for progression to more severe hypersensitivity reactions, the masking of early warning signs of serious allergic events, and the additive burden of adverse effects from both drug classes.

GLP-1 RAs are associated with a spectrum of hypersensitivity reactions, including rare but potentially severe cutaneous and systemic events. While mild rashes may be managed symptomatically, continued exposure carries a risk of escalation to more severe reactions, which may not be fully prevented or predicted by antihistamine use. Antihistamines may blunt pruritus and rash, potentially delaying recognition of a worsening response, but do not prevent severe or life-threatening hypersensitivity, including anaphylaxis, which has been reported at a modestly increased rate with GLP-1 RAs compared to other agents.[3] [4] This calls for strict medical supervision of these agents, particularly relevant in regions where access without prescription is feasible.

Long-term GLP-1 RA therapy is also associated with gastrointestinal adverse effects, increased risk of gallbladder disease, and other rare events.[11] [12] Chronic antihistamine use, particularly first-generation agents, may cause sedation, cognitive impairment, and anticholinergic effects, especially in older adults. No data support that antihistamines mitigate the risk of severe allergic or systemic reactions to GLP-1 RAs. Gastroenterology and cardiology professional bodies recommend discontinuation of GLP-1 RAs if serious hypersensitivity reactions occur, and continued therapy after allergic reactions is not a standard practice.[9] [10] [11] [12] [13] [14] [15] [16] [17]


 

Follow-up on the Case

Along the lines discussed earlier, the physician had a full discussion of the legal and ethical aspects of the case on three different occasions. The therapeutic options which were considered included (1) stopping the tirzepatide and (2) changing to semaglutide, or continuing on the tirzepatide co-administered with an antihistamine (which was already started by the patient on her own accord!). The patient expressed a strong wish to continue tirzepatide with an antihistamine. The risk of developing a more serious reaction despite the concurrent use of antihistamine therapy was explained. However, the patient did not lose more weight in the following 6 weeks despite increasing the dose to 7.5 and 10 mg. This slowing could be part of the plateauing phenomenon observed with the use of this class. Nonetheless, given the persistence of the skin reaction, the risk started to outweigh the likely benefit; it was mutually agreed to stop tirzepatide and consider other options.


 

Conclusion

The key messages from this case are presented in [Box 2]. This case illustrates the complex interplay of ethics, law, and clinical judgment when managing allergic reactions to medications such as tirzepatide. While continuation of tirzepatide after hypersensitivity reactions is not the standard of care, it may be ethically permissible under specific, carefully monitored conditions. Clinicians must weigh the benefits against unpredictable risks, prioritize transparent communication with patients, and rigorously document their decision-making process.

Box 2

Key messages

1. Continuing a GLP-1 RAs after a mild to moderate allergic reaction, with antihistamine cover, is a carefully individualized decision, supported only for benign, non-IgE-mediated cutaneous reactions, with close monitoring and informed consent

2. The populations most likely to benefit are those with severe obesity and/or significant comorbidities, limited alternatives, and a mild, non-progressive allergic reaction that is manageable with antihistamines

3. The primary long-term safety concern is the risk of unrecognized or escalating hypersensitivity, which may be masked by antihistamines, alongside the known adverse effect profiles of both drug classes

GLP-1 RAs: glucagon-like peptide-1 receptor agonists

 

 

Conflict of Interest

None declared.

Authors' Contributions

Single author responsible for all aspects of the article.


Compliance with Ethical Principles

Prior ethical approval is not required for the publication of single cases.


Patient's Consent

The patient provided permission for the use of the clinical history and images for publication on an anonymous basis.



Address for correspondence

Salem A. Beshyah, MBBCh, DIC, MRCP, PhD
Department of Medicine, Bareen International Hospital
MBZ City, MBZ1507, Abu Dhabi
United Arab Emirates   

Publikationsverlauf

Artikel online veröffentlicht:
10. September 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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Zoom
Fig. 1 The evolution of the skin reaction on days 1, 2, and 5 of a single injection.
Zoom
Fig. 2 A similar type and severity of the reaction occurred in different parts of the body in response to two consecutive injections.