Acute Deep Vein Thrombosis in the Setting of Tirzepatide Use: A Case Highlighting Emerging Concerns

Abstract

Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 agonist, is gaining popularity for its weight reduction, improved glycemic control, and cardiorenal benefits. While it is generally well tolerated, thrombotic events have not been commonly reported. We report a case of a woman who developed an unprovoked deep vein thrombosis within months of starting tirzepatide. An extensive hypercoagulability workup was negative. Her symptoms improved with anticoagulation and discontinuation of tirzepatide. This case highlights a potential risk of thromboembolic events associated with tirzepatide. Clinicians need to be vigilant and exercise extreme caution as the emerging adverse event profile of this novel medication unfolds.

Introduction

Tirzepatide—a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist—has demonstrated significant improvements in glycemic control and weight reduction in patients with type 2 diabetes [1]. SURMOUNT-1 trial reported substantial, sustained weight loss in individuals with obesity treated with tirzepatide [2]. In addition, tirzepatide has also shown promising cardiovascular outcomes [3]. Beyond its approved indications, tirzepatide has gained considerable popularity for vanity-driven weight loss. As with any medication, tirzepatide may cause adverse drug reactions. Common side effects associated with tirzepatide include gastrointestinal symptoms such as nausea, vomiting, abdominal pain, diarrhea, and constipation. More serious but less frequent adverse events include acute pancreatitis, cholelithiasis, acute renal failure, and injection site reactions [4].

According to data from the Centers for Disease Control and Prevention, venous thromboembolism (VTE) affects up to 900 000 individuals in the United States each year. The 2020 Global Burden of Disease Project did not classify deaths from VTE as a distinct category [5], highlighting a broader lack of awareness surrounding this potentially life-threatening condition. In this report, we describe a case of a young woman on tirzepatide for weight loss; she developed acute deep vein thrombosis (DVT) requiring hospitalization. This case highlights the importance of considering uncommon side effects of this now commonly used medication. As tirzepatide continues to garner wider popularity, clinicians need to be vigilant about its evolving side effect profile. We also discuss the possible pathophysiology of how tirzepatide could increase the risk of VTE.

Case Presentation

A 57-year-old Class 3 obese woman with a history of left breast cancer in remission presented to the emergency department with a 2-day history of acute pain and swelling in her left upper extremity. She reported an 8-month history of using subcutaneous tirzepatide 10 mg once weekly for weight loss. She denied any recent immobility, travel, surgery, lymphedema, smoking, or illicit drug use. There was no personal or family history of thromboembolic events or autoimmune disorders. She also reported no history of miscarriages or previous episodes of superficial or DVT.

Breast cancer was diagnosed 12 years ago as stage II triple-negative breast cancer, for which she underwent a mastectomy. She has remained in remission since and continues regular oncology follow-up, with her most recent visit occurring 1 month prior to presentation.

Diagnostic Assessment

Upon thorough examination, the patient was hemodynamically stable, with a weight of 105.68 kg and a body mass index of 45.5 kg/m². Vitals were stable. Physical examination revealed erythema, warmth, diffuse swelling, and tenderness to palpation of the left upper extremity. No axillary lymphadenopathy, joint swelling, or skin rash was noted. Laboratory findings are summarized in Table 1. Duplex ultrasound of the left upper extremity demonstrated an occlusive DVT of the left subclavian vein (Fig. 1). An extensive hypercoagulable workup was unremarkable (Table 2).

Table 1.

Laboratory findings during hospitalization

Laboratory investigations	Day of admission	Day of discharge	Reference range (conventional/SI units)
WBC	6.5 × 10⁹/L	5.6 × 10⁹/L	3.7-10.6 × 10⁹/L
Hemoglobin	12.5 g/dL (125 g/L)	11.0 g/dL (110 g/L)	11.0-14.9 g/dL (110-149 g/L)
Hematocrit	36.6%	32.1%	32.6-43.4%
Platelet count	342 × 10⁹/L	265 × 10⁹/L	130-351 × 10⁹/L
Sodium	139 mmol/L	138 mmol/L	137-145 mmol/L
Potassium	3.8 mmol/L	4.3 mmol/L	3.5-5.1 mmol/L
Chloride	103 mmol/L	105 mmol/L	98-107 mmol/L
Carbon dioxide	26 mmol/L	29 mmol/L	21-32 mmol/L
BUN	20 mg/dL (7.14 mmol/L)	18 mg/dL (6.43 mmol/L)	7-20 mg/dL (2.5-7.1 mmol/L)
Creatinine	0.6 mg/dL (53 µmol/L)	0.85 mg/dL (75 µmol/L)	0.52-1.04 mg/dL (46-92 µmol/L)
Glucose	125 mg/dL (6.94 mmol/L)	166 mg/dL (9.21 mmol/L)	70-109 mg/dL (3.9-6.0 mmol/L)
Calcium	9.8 mg/dL (2.45 mmol/L)	9.4 mg/dL (2.35 mmol/L)	8.4-10.2 mg/dL (2.10-2.55 mmol/L)
Total bilirubin	0.4 mg/dL (6.8 µmol/L)	—	0.2-1.3 mg/dL (3.4-22.2 µmol/L)
AST	29 U/L	—	3-45 U/L
ALT	30 U/L	—	0-35 U/L
Alkaline Phosphatase	113 U/L	—	38-126 U/L
Albumin	4.5 g/dL (45 g/L)	—	3.5-5.0 g/dL (35-50 g/L)
CRP	8.9 mg/L	—	<10 mg/L

Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; CRP, C-reactive protein; WBC, white blood cell count.

Figure 1.

An ultrasound image showing deep vein thrombosis of left subclavian vein; demonstrated by arrows.

Table 2.

Laboratory investigations to evaluate hypercoagulability

Investigations	Results	Normal range (conventional/SI units)
Protein S activity	99	65-150% (functional activity)
Protein C activity	173	70-150% (functional activity)
Antithrombin III antigen	91	80-120% (antigen level)
Antithrombin III activity	110	80-130% (functional activity)
Factor V Leiden mutation	Negative	Negative
Factor V mutation	Negative	Negative
Factor VIII activity	162	55-200% (functional activity)
Homocysteine	9.6 µmol/L	4.7-12.6 µmol/L
Beta-2 GPI IgG antibody	<2.0	< 20 U/mL antibody not detected
Beta-2 GPI IgM antibody	<2.0	< 20 U/mL antibody not detected
Beta-2 GPI IgA antibody	6.9	<20 U/mL antibody not detected
Prothrombin IgG antibody	<20	<20 antibody not detected
Phosphatidylserine IgM Antibody	10	< 30 U
Phosphatidylserine IgG Antibody	<9.0	<30 U
Anti-cardiolipin IgG Antibody	<2.0	<20 U/mL antibody not detected
Anti-cardiolipin IgA Antibody	9.3	<20 U/mL antibody not detected
Anti-cardiolipin IgM Antibody	<2.0	<20 U/mL antibody not detected
Prothrombin G20210A Mutation	Negative	Negative
Lupus anticoagulant panel	Negative	Negative

Treatment

The patient's symptoms began to improve after initiating empiric IV antibiotics (vancomycin and piperacillin-tazobactam) and subcutaneous enoxaparin 110 mg twice daily. Antibiotics were discontinued once DVT was confirmed as a cause of her symptoms, and blood cultures showed no growth. Upon discharge, she was advised to discontinue tirzepatide. She was prescribed apixaban 10 mg orally twice daily for 1 week, followed by 5 mg twice daily.

Outcome and Follow-up

During a follow-up call 3 months later, the patient reported discontinuing tirzepatide and noted near-complete resolution of symptoms, feeling fully recovered to her usual state.

Discussion

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist approved for the treatment of type 2 diabetes and chronic weight management. In recent years, use of tirzepatide and other GLP-1 receptor agonists has surged beyond their approved clinical indications, particularly for weight loss driven by cosmetic reasons. While there is substantial data on the common adverse effects of tirzepatide, its potential association with VTE remains an area of emerging research. A review of the US FDA Adverse Event Reporting System showed a sharp increase in tirzepatide-related adverse event reports, rising from 3125 in 2022 to over 37 000 by 2024.

To date, only a few reports have suggested a possible link. A recently published report described extensive lower extremity DVT in a young male using tirzepatide for weight loss [6]. In that report, the patient presented with a left lower extremity DVT, whereas our patient developed a left upper extremity DVT. The demographic profiles also differ significantly: the former involved a 20-year-old male, while our case describes a 57-year-old female. Notably, neither patient had a personal or family history of thromboembolic events, nor did they report common risk factors such as recent travel, immobilization, or recent surgical procedures. In terms of management, the patient in the prior report underwent mechanical thrombectomy followed by anticoagulation, whereas our patient was managed exclusively with anticoagulation therapy, without the need for invasive intervention.

Another study found that semaglutide use was associated with a 266% increased risk of DVT (relative risk 3.66) [7]. Similarly, a recent study reported GLP-1 receptor agonist use during total shoulder arthroplasty was linked to an increased risk of DVT (odds ratio 3.0; P = .001) [8]. In contrast, another study showed GLP-1 agonist use in patients with type 2 diabetes was associated with lower VTE rates after 1 year [9]. However, this protective effect may be attributed to improved glycemic control—since diabetes itself is a known risk factor for VTE—and may not reflect a direct benefit of the medication. Importantly, these findings may not be generalizable to the nondiabetic population.

Our patient developed occlusive DVT in the left upper extremity. Her weight had been quite stable for the past several years prior to initiation of tirzepatide. Given the timing of the adverse event after starting tirzepatide, the absence of other contributing factors, and a nondiagnostic hypercoagulable workup, tirzepatide was considered a potential contributor to the development of DVT in this patient.

Naranjo et al developed a systematic method, known as the Naranjo Scale, to estimate the probability of adverse drug reactions. This scale consists of 10 questions, yielding a total score ranging from −4 to +13. Based on the score, the likelihood of a drug-related adverse event is categorized as doubtful (≤ 0), possible (1-4), probable (5-8), or definite (≥ 9) [10]. In our case, the patient scored 6, indicating a probable association between tirzepatide use and the development of DVT.

Obesity is a well-established risk factor for the development of VTE. A prospective cohort study confirmed this association [11]. Interestingly, 1 striking finding from the study was that obese individuals who experienced weight loss also showed an elevated risk of VTE, like in our patient who experienced weight loss over a short duration of time after initiating tirzepatide.

Additionally, dehydration—commonly observed in patients using tirzepatide due to reduced appetite and decreased oral intake—and venous stasis associated with obesity, as seen in our patient, are well-established risk factors for VTE. A history of breast cancer further compounded her risk. Population-based studies have also demonstrated that chronic inflammation in individuals with obesity contributes to a prothrombotic state, with increased production of coagulation factors such as plasminogen activator inhibitor-1, fibrinogen, tissue factor, and factor VIII, all of which promote thrombus formation [12].

A combination of these factors may represent a plausible mechanism underlying the development of DVT in our patient. However, the exact pathophysiological link remains limited and unclear. Although our patient had several risk factors for the development of DVT, including Class 3 obesity, a history of breast cancer, dehydration, and rapid weight loss, these factors must be carefully considered. Their presence does not establish a causal relationship between tirzepatide use and the development of DVT. Further research is needed to explore the potential causal relationship between tirzepatide and VTE. It also remains unclear whether this risk is specific to certain agents within the class or represents a broader class effect. A key limitation of our report is its single-patient nature, which precludes broader generalization.

Large randomized controlled trials, such as SURMOUNT [3] and SURPASS [1], have not identified an increased risk of VTE or DVT associated with tirzepatide or other GLP-1 receptor agonists. It is important to explicitly acknowledge the absence of thromboembolic events in these extensive clinical datasets. As such, our case report—while noteworthy—cannot establish a causal relationship between tirzepatide use and the development of upper extremity DVT. Rather, it serves to highlight the rarity of this event and underscores the need for continued pharmacovigilance.

There is strong scientific evidence supporting the benefits of tirzepatide and other GLP-1 receptor agonists. However, a thorough risk assessment is essential before initiating therapy, and high-risk patients need close monitoring. Patients should be educated to recognize symptoms of VTE and to promptly report them to their physicians. As the use of GLP-1 agonists becomes increasingly widespread, greater awareness of VTE as a potential adverse effect is critical for both clinicians and patients.

Learning Points

• The adverse effect profile of tirzepatide continues to evolve as its use expands, particularly for weight management.

• Tirzepatide may be associated with an increased risk of DVT, especially in individuals with predisposing risk factors.

• Clinicians should remain vigilant about the growing list of reported side effects to ensure prompt recognition and management.

Contributors

All authors made substantial individual contributions to the manuscript. K.S. was directly involved in the diagnosis and management of the patient. K.S. and P.S. were responsible for the conceptualization, design, and primary drafting of the manuscript. G.A., B.A., S.P., and H.P. contributed to the interpretation of clinical findings and critically revised the manuscript for important intellectual content. P.S. supervised the entire process and coordinated the final submission. All authors reviewed and approved the final version of the manuscript and agree to be accountable for all aspects of the work, ensuring that any questions related to accuracy or integrity are appropriately addressed.

Funding

No public or commercial funding.

Disclosures

None of the coauthors have declared any conflict of interest.

Informed Patient Consent for Publication

Signed informed consent obtained directly from patient.

Data Availability Statement

Original data generated and analyzed for this case report are included in this published article.