Rare Liraglutide-Induced Dermatological Adverse Reaction in the Treatment of Obesity

Abstract

Liraglutide is a glucagon-like peptide-1 (GLP-1) agonist widely used for managing type 2 diabetes mellitus and obesity. Although allergic reactions to the drug have been documented, skin-related adverse effects remain underreported. We present a case of a 43-year-old woman undergoing subcutaneous liraglutide injections for obesity treatment. Approximately 3 weeks into the treatment regimen, the patient experienced a distinctive reaction characterized by oval, red erythema accompanied by swelling, itchiness, and skin warmth around the injection site shortly after drug administration. This reaction recurred with each subsequent dose over the next 3 days, prompting the patient to discontinue treatment. A dermatology consultant suggested oral antihistamines in conjunction with topical methylprednisolone. Over the course of several days, the intensity of the skin lesions gradually decreased, ultimately resolving completely within 1 month. This case highlights the rarity of skin adverse reactions associated with liraglutide and underscores the importance of recognizing and managing injection site erythema as a potential side effect of this medication. Further research is needed to better understand and document such reactions for improved patient care and safety.

Keywords

diabetes mellitus - drug-induced skin reaction - glucagonlike peptide-1 - obesity treatment

Introduction

Obesity remains a pervasive and challenging health concern, with far-reaching implications for individuals and public health systems worldwide. Liraglutide is a glucagonlike peptide-1 (GLP-1) receptor agonist used in patients with type 2 diabetes mellitus to improve glycemic control and weight management. The Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved the diabetes drug liraglutide to treat obesity.[1] [2] Patients without type 2 diabetes showed a sustained effect on weight loss using doses up to 3.0 mg of liraglutide.[3] A subcutaneous injection can be given in the abdomen, thigh, or upper arm. Skin-related side effects are rarely reported in those patients, mainly characterized by rash and pruritus during postapproval use.[4] [5] We are reporting a case of liraglutide-induced dermatological drug reactions used in the treatment of obesity.

Case Report

A 43-year-old woman with no history of type 2 diabetes mellitus and weight of 102 kg, height of 163 cm, and body mass index of 38.42 kg/m² was diagnosed with obesity and treated with liraglutide administered subcutaneously. The initial dose was 0.6 mg daily during the first week, and it was increased gradually every week by 0.6 mg/d to reach the maximum therapeutic dose of 3 mg/d. On getting the weekly dose of 3 mg daily, the patient developed some itching at the injection site. However, after a day of injection she developed erythematous patches at the injection sites. On cutaneous examination, there were bilateral erythematous well-defined plaques. The lesions had developed gradually and progressively on the abdomen and the leg at the injection sites of liraglutide ([Figs. 1] [2] [3] [4]).

Fig. 1 After 10 subcutaneous injections of 3.0-mg dose of Saxenda, the reactions were clearly in their maximum expression.

Fig. 2 The patients changed the application site to legs, with the same kind of cutaneous reaction again.

Fig. 3 The reaction remained after 5 days of the first picture.

Fig. 4 Evidence of the cutaneous response was still visible on the injection site 6 weeks after the first picture.

Although the patient had a history of mild atopy, hypothyroidism, and hypertension, she did not suffer from any medication or food allergies, and she was not taking other regular medications apart from levothyroxine 75 µg/d. Laboratory blood test results are shown in the [Table 1]. On follow-up examination, 2 weeks later the rash did not resolve, and 5 weeks later, they disappeared, leaving deeply seated, firm nodules at the same site ([Fig. 5]). No biopsy was obtained. The patient was diagnosed with a delayed allergy to liraglutide.

Fig. 5 The bilateral erythematous well-defined plaques disappeared 7 weeks after the last injection.

Table 1 Blood test results were done 1 week after the initial cutaneous reaction appeared

Marker	Units	Normal range
Erythrocyte sedimentation rate (ESR)	45 mm/h	0–29 mm/h
Glucose	5.94 mmol/L	3.9–5.6 mmol/L
Triglycerides	1.41 mmol/L	<1.69 mmol/L
Alanine aminotransferase (ALT)	13 U/L	4–36 U/L
Aspartate aminotransferase (AST)	18.0 U/L	8–33 U/L
Gamma-glutamyl transferase (GGT)	38.0 U/L	5–36 U/L
Creatinine	76.0 µmol/L	53–114.9 µmol/L
Uric acid	336.0 µmol/L	154.6–356.8 µmol/L
Amylase	57.0 U/L	<110 U/L
From the complete blood count (CBC)
Hemoglobin	128 g/L	115–165 g/L
White blood cells (WBC)	6.6 × 109/L	4–11 × 109/L
Lymphocytes	2.1 × 109/L	1.5–4.5 × 109/L
Monocytes	0.5 × 109/L	0.2–0.8 × 109/L
Polymorphonuclear leukocytes	4.0 × 109/L	0–1.2 × 109/L

Discussion

The most common adverse reactions of liraglutide are nausea, vomiting, and diarrhea. There is still a risk of other rare but serious side effects like pancreatitis, thyroid cancer, and gall stones,[6] and side effects are mainly related to the gastrointestinal system. However, several cases of adverse skin reactions have been reported, for instance a vesiculopustular rash,[7] acute exanthematous pustulosis,[8] and generalized erythematous plaques and nodules,[9] associated with liraglutide treatment. Injection site reactions are listed as adverse drug reaction of liraglutide. However, the product literature does not specify whether its onset is immediate or delayed.[10]

Allergic reactions to GLP-1 receptor agonists (GLP-1RAs) have been described in the literature. Shamriz et al[11] reported a case of anaphylaxis after a first dose of lixisenatide, with an immediate positive intradermal test result to this drug and to exenatide, which the patient had previously received. However, skin tests with liraglutide, which she had also received, were negative. The patient later tolerated the drug. The authors attributed this to the molecular differences between the two exendin-4-based drugs—exenatide and lixisenatide—and the human GLP-1 analog, liraglutide. Homology between exendin-4-based GLP-1RAs and human GLP-1 is approximately 53%, thus potentially explaining the patient's tolerance to liraglutide, which has 97% homology with human GLP-1.[12] Only one confirmed hypersensitivity reaction to liraglutide with positive skin test results has been reported.[13] The symptoms observed in our case—pruriginous macules at the injection sites—were compatible with a delayed hypersensitivity reaction to liraglutide and resolved 5 weeks after discontinuation without residual skin lesions. In contrast with previously reported cases, no other associated skin lesions, such as pustules or nodules, were present.

Conclusion

The present case showed that unusual, delayed hypersensitivity localized skin reactions may occur following subcutaneous administration of liraglutide.

Conflict of Interest

None declared.

Patient Consent Statement

The authors certify that they have obtained all appropriate patient consent forms, including the format for her images and other clinical information to be reported in the publication. The patient understands that her name and initials will not be published and that every effort will be made to conceal their identity, even when anonymity cannot be guaranteed.

Authors' Contributions

M.M.A. contributed to conception and design of the study; acquisition, analysis, and interpretation of data; and drafting of the manuscript; and final approval of the submitted version of the manuscript. G.R.N. and R.A.R.J. contributed to analysis and interpretation of data, drafting of the manuscript, and final approval of the submitted version of the manuscript.

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Publication History

Article published online:
12 August 2024