Successful Reversal of Tamoxifen-Associated Weight Gain and Metabolic Dysfunction with Liraglutide in a Breast Cancer Survivor: A Case Report

Abstract

Introduction: Adjuvant endocrine therapy for breast cancer - particularly tamoxifen - is commonly associated with weight gain, increased adiposity, and metabolic dysfunction. Lifestyle measures often fail to reverse these effects. Evidence regarding glucagon-like peptide-1 (GLP-1) receptor agonists in this specific context remains limited. Reversal of tamoxifen-associated weight gain with liraglutide has been rarely reported. Case Presentation: A 58-year-old postmenopausal woman with stage IIA, hormone-receptor positive breast cancer experienced marked weight gain after 24 months of tamoxifen therapy, despite diet and exercise. She developed prediabetes, insulin resistance (assessed by Homeostatic Model Assessment of Insulin Resistance [HOMA-IR] 4.9), and dyslipidemia. Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, was initiated and titrated to 3.0 mg/day. Over 12 months, she lost 18.5 kg, and her metabolic parameters, including HOMA-IR and glycated hemoglobin (HbA1c), normalized. Tamoxifen therapy was continued without adverse effects. Conclusion: This case suggests that liraglutide may reverse substantial tamoxifen-associated weight gain and related metabolic derangements in a breast cancer survivor. The observed improvement exceeded what is typically achieved with lifestyle measures alone. Formal studies are needed to define the role of GLP-1 receptor agonists in managing endocrine therapy–related metabolic complications.

Introduction

Adjuvant endocrine therapy (e.g., tamoxifen) is standard for hormone-receptor positive breast cancer but often causes weight gain and metabolic disturbances. Over two-thirds of women gain weight after diagnosis, and obesity at diagnosis is a known risk factor for higher recurrence and mortality. ¹ Obesity may also worsen breast cancer progression via hormonal dysregulation, chronic inflammation, adipokine imbalance, and insulin/IGF signalling. ² Endocrine agents themselves may contribute to these changes. Tamoxifen and aromatase inhibitor use has been linked to increased adiposity and insulin resistance; survivors of these therapies often report significant weight gain and higher type 2 diabetes risk, especially if obese. These findings are consistent with animal and small clinical studies showing tamoxifen-induced impairments in glucose tolerance and lipid metabolism. Taken together, endocrine-therapy–associated weight gain may contribute to a metabolic syndrome–like state, exacerbating cardiovascular and cancer risks. ³

Weight management in breast cancer survivors is challenging, as lifestyle interventions typically yield modest, hard-to-sustain losses (≈4–6% at 1 year). GLP-1 receptor agonists, such as liraglutide, are effective pharmacologic options, delaying gastric emptying and enhancing satiety to produce substantial weight reduction (phase 3 trials: 8–15%, most ≥5%). In a retrospective cohort of 75 survivors (median BMI 34), mean weight fell ∼5% at 12 months, comparable to behavioral trials, regardless of concurrent endocrine therapy. GLP-1 receptor agonists thus offer a promising adjunct for obesity management in this population.^1-3

Tamoxifen-induced weight gain reversal with a GLP-1 receptor agonist has been rarely reported. It remains unknown whether GLP-1 receptor agonists can achieve the same degree of weight loss in breast cancer patients on endocrine therapy as in the general population. Our patient’s dramatic weight reduction during liraglutide therapy highlights this gap in the literature and suggests that potent GLP-1 receptor agonists treatment can overcome tamoxifen’s weight-promoting effects. We present this unique case to illustrate a potentially underutilized strategy for managing severe endocrine-therapy associated obesity. ¹

Case Presentation

A 58-year-old postmenopausal woman was diagnosed with stage IIA (pT2 pN0 M0), estrogen receptor-positive (95%), progesterone receptor-positive (80%), HER2-negative invasive ductal carcinoma of the left breast. Her past medical history was significant only for well-controlled hypertension treated with lisinopril 10 mg daily. She had no personal history of diabetes or thyroid disease. Her family history was non-contributory. Secondary causes of weight gain were formally evaluated and excluded. The patient had normal thyroid function tests (TSH 2.1 μIU/mL, free T4 1.2 ng/dL), normal morning cortisol (12 μg/dL), and no clinical features suggestive of Cushing syndrome. Screening for sleep disorders, including obstructive sleep apnea, was negative based on patient history and the STOP-Bang questionnaire (score 2/8).

Her initial treatment included lumpectomy, sentinel lymph node biopsy, and adjuvant chemotherapy (four cycles of doxorubicin/cyclophosphamide). This was followed by adjuvant radiotherapy and initiation of tamoxifen 20 mg daily. Prior to starting chemotherapy, her weight was stable at 82 kg, with a BMI of 29.8 kg/m².

At her 24-month follow-up appointment while on tamoxifen, she reported profound frustration over a 15 kg weight gain (current weight 97 kg, BMI 34.2 kg/m²) despite dedicated efforts, including caloric restriction to ∼1500 kcal/day and moderate-intensity exercise (brisk walking, 30 minutes, 5 days/week). Dietary intake was monitored using patient-maintained food diaries and periodic 24-hour dietary recall during follow-up visits. Physical activity was tracked using a commercially available wearable fitness device that recorded daily step count and walking duration, allowing objective confirmation of adherence to the prescribed activity regimen. She reported increased cravings, especially for carbohydrates, and a constant sensation of hunger. She expressed significant distress, fearing the weight would impact her cancer prognosis. Physical examination revealed a blood pressure of 128/78 mmHg, a pulse of 72 bpm, and a waist circumference of 108 cm. Acanthosis nigricans were noted on the posterior neck. The remainder of the exam was unremarkable.

Baseline laboratory studies were performed and compared to her pre-tamoxifen labs (available from her initial oncology workup). The results are summarized in Table 1. Laboratory tests obtained after 24 months of tamoxifen therapy revealed significant metabolic deterioration, including pre-diabetes (elevated fasting glucose and HbA1c), significant insulin resistance (HOMA-IR of 4.9), and mixed dyslipidemia (elevated LDL, low HDL, elevated triglycerides).

Table 1.

Laboratory Parameters before and after 24 Months of Tamoxifen, and after 12 Months of Liraglutide Intervention

Laboratory parameter	Pre-tamoxifen (baseline)	After 24 Months tamoxifen (pre-GLP-1)	After 12 Months liraglutide + tamoxifen	Reference range
Weight (kg)	82.0	97.0	78.5	-
BMI (kg/m2)	29.8	34.2	28.1	18.5 - 24.9
Waist Circumference (cm)	92	108	88	< 80 cm (Women)
Fasting Glucose (mg/dL)	92	108	90	70 - 99
HbA1c (%)	5.4	6.0	5.3	4.0 - 5.6
Fasting Insulin (µIU/mL)	8.0	18.5	7.5	2.6 - 24.9
HOMA-IR	1.8	4.9	1.7	< 2.5
Total Cholesterol (mg/dL)	185	235	175	< 200
LDL-C (mg/dL)	105	155	95	< 100
HDL-C (mg/dL)	48	42	52	> 50
Triglycerides (mg/dL)	160	190	140	< 150
ALT (U/L)	22	28	20	7 - 35
AST (U/L)	20	24	19	8 - 32
Morning Cortisol (µg/dL)	12	13	11	5 - 25
TSH (mIU/L)	2.1	2.3	2.2	0.4 - 4.5

Abbreviations: BMI: Body Mass Index; HOMA-IR: Homeostatic Model Assessment of Insulin Resistance; LDL-C: Low-Density Lipoprotein Cholesterol; HDL-C: High-Density Lipoprotein Cholesterol; ALT: Alanine Aminotransferase; AST: Aspartate Aminotransferase; TSH: Thyroid-Stimulating Hormone.

All laboratory measurements were performed in the same certified laboratory using standardized methods. No adverse events or oncologic complications occurred during follow-up.

After a multidisciplinary discussion involving oncology, endocrinology, and the patient, a decision was made to initiate liraglutide (Saxenda®) for weight management, with the goal of mitigating metabolic risk while allowing for the uninterrupted continuation of tamoxifen. Liraglutide was chosen over other GLP-1 receptor agonists due to its established efficacy for weight management at the 3.0 mg/day dose, extensive safety data in patients with cardiovascular risk factors, once-daily dosing, and clinician familiarity. The decision was also guided by patient preference for a therapy with the longest published experience in obesity management. The liraglutide regimen was initiated at 0.6 mg subcutaneously daily and titrated weekly by 0.6 mg, as per the standard schedule, to a target dose of 3.0 mg daily. The complete chronological sequence of the patient’s cancer treatment, tamoxifen therapy, liraglutide initiation and dose escalation, and subsequent clinical outcomes is summarized in Table 2. The patient was counseled on a balanced, reduced-calorie diet and advised to maintain her existing exercise routine. She was monitored for side effects, particularly gastrointestinal symptoms. The patient tolerated the titration well, experiencing only mild, transient nausea during the first two weeks at the 1.2 mg and 1.8 mg doses, which resolved spontaneously. Adherence to liraglutide therapy was assessed through patient self-report, review of injection pen usage, and confirmation during scheduled follow-up visits.

Table 2.

Chronologic Medication and Treatment Timeline for the Reported Patient. Dates are Reported Relative to Cancer Diagnosis and Treatment Milestones; Liraglutide Titration Follows the Standard Weekly Escalation to 3.0 mg Daily

Time point/Date	Treatment/Medication	Dose/Schedule	Notes/outcome
Baseline (pre-chemotherapy/pre-tamoxifen)	—	—	Weight 82 kg (BMI 29.8 kg/m2); labs normal for baseline.
Month 0 — Diagnosis; surgery	Lumpectomy + sentinel LN biopsy	Per surgical protocol	Pathology: pT2 pN0 M0, ER 95%/PR 80%/HER2–.
Months 1–4	Adjuvant chemotherapy — doxorubicin + cyclophosphamide (AC)	4 cycles (standard dosing per oncology record)	Completed without unexpected complications.
Months 5–6	Adjuvant radiotherapy	Completed per oncology record	—
Month 6 — endocrine therapy start	Tamoxifen	20 mg orally once daily, continued throughout follow-up	At initiation weight 82 kg.
Month 24 (while on tamoxifen)	—	—	The patient reported 15 kg gain → weight 97 kg (BMI 34.2). Labs: prediabetes, HOMA-IR 4.9, mixed dyslipidemia.
Month 24 — liraglutide initiation (post multidisciplinary review)	Liraglutide (Saxenda®) — start	0.6 mg SC daily (week 1)	Adherence monitored via pen review, patient logs, clinic visits.
Week 2 (liraglutide titration)	Liraglutide	1.2 mg SC daily	Mild transient nausea reported.
Week 3 (liraglutide titration)	Liraglutide	1.8 mg SC daily	Nausea resolved spontaneously.
Week 4 (liraglutide titration)	Liraglutide	2.4 mg SC daily	Tolerated.
Week 5 onward (maintenance)	Liraglutide	3.0 mg SC daily (maintenance)	Continued for at least 12 months with good adherence.
12 months after liraglutide start	—	—	Weight 78.5 kg (–18.5 kg from peak; BMI 28.1). HOMA-IR 1.7; HbA1c and lipid panel normalized. Tamoxifen continued without adverse interaction.

AC: doxorubicin plus cyclophosphamide; BMI: body mass index; ER: estrogen receptor; GLP-1 RA: glucagon-like peptide-1 receptor agonist; HbA1c: hemoglobin A1c; HOMA-IR: homeostatic model assessment of insulin resistance; HDL: high-density lipoprotein; LDL: low-density lipoprotein; LN: lymph node; PR: progesterone receptor; SC: subcutaneous.

At the 12-month follow-up on liraglutide, the patient’s weight was 78.5 kg, representing a total loss of 18.5 kg from her peak and 3.5 kg below her pre-tamoxifen weight. Her BMI normalized to 28.1 kg/m². Repeat laboratory studies demonstrated a complete reversal of her metabolic abnormalities (Table 1). Her HOMA-IR normalized to 1.7, and her lipid panel improved significantly. Subjectively, she reported dramatically reduced appetite and food cravings, improved energy levels, and a markedly enhanced quality of life and body image. Tamoxifen was continued without issue.

The patient’s trajectory in body weight and glycemic control over the three-year period is illustrated in Figure 1, which highlights the marked reversal of tamoxifen-associated metabolic deterioration following liraglutide initiation. Corresponding changes in body composition and laboratory markers, including HOMA-IR and lipid parameters, are summarized in Figure 2, demonstrating improvement not only relative to pre-GLP-1 values but also surpassing baseline pre-tamoxifen measurements.

Figure 1.

Trend in Body Weight and HbA1c Over Time: A line graph depicting time on the x-axis (0 to 36 months) and two y-axes: Weight (kg) on the left and HbA1c (%) on the right.

• Weight (kg): The line starts at 82 kg (Pre-Tamoxifen). It rises steadily to 97 kg at 24 months (Pre-GLP-1). Upon initiation of liraglutide (marked with a vertical dashed line at 24 months), the line declines sharply, reaching 78.5 kg at 36 months (12 months post-liraglutide).

• HbA1c (%): The line starts at 5.4%, rises to 6.0% at 24 months, and falls back to 5.3% at 36 months after liraglutide initiation

Figure 2.

Change in Body Composition and Metabolic Markers: A bar chart comparing key parameters at three time points: Pre-Tamoxifen, Pre-GLP-1, and Post-GLP-1.

• Bars for Weight (kg): 82, 97, 78.5.

• Bars for HOMA-IR: 1.8, 4.9, 1.7.

• Bars for LDL-C (mg/dL): 105, 155, 95. The chart visually emphasizes the deterioration after tamoxifen and the marked improvement after liraglutide, even beyond baseline

Over the span of two years, the patient watched her body change in ways she felt powerless to stop. Despite her efforts, the weight gain continued, fueling a deep fear that it might increase her risk of cancer recurrence. Beginning the new medication marked a pivotal shift. For the first time in years, she experienced a sense of control over her appetite. The subsequent weight loss became more than a physical transformation—it helped restore her confidence and renewed her hope for a healthier future beyond cancer.

Discussion

Weight gain is a frequent and underrecognized consequence of adjuvant endocrine therapy in breast cancer. Observational studies suggest that women receiving tamoxifen have higher odds of post-diagnosis weight gain, which may contribute to insulin resistance, dyslipidemia, and other metabolic abnormalities. In our patient, two years of tamoxifen therapy coincided with substantial weight gain and development of prediabetes and dyslipidemia, illustrating how endocrine-therapy associated weight gain may contribute to a metabolic syndrome–like state.^1,4

Lifestyle interventions remain the cornerstone of weight management in breast cancer survivors, although their impact is often modest, with average weight reductions of approximately 4–6% at one year in clinical trials. GLP-1 receptor agonists represent a pharmacologic option that promotes weight loss through appetite suppression and delayed gastric emptying. Early observational studies in breast cancer survivors suggest modest reductions in body weight (approximately 2–5% at 12 months), even in patients receiving concurrent endocrine therapy. In the present case, liraglutide treatment resulted in substantially greater weight loss, with a reduction of approximately 19% of peak body weight and normalization of metabolic parameters.^1-5

Other weight-management strategies warrant brief mention. Metformin is sometimes used off-label to address insulin resistance and modest weight gain in breast cancer patients. It may also have additive antitumor effects with tamoxifen, but on its own metformin tends to induce only minimal weight loss and did not form part of our patient’s regimen. ⁶ Lifestyle intervention remains cornerstone therapy; however, as noted, its effect size is often small and many patients (especially those postmenopausal or on endocrine therapy) struggle to meet weight goals.^1,6 Emerging GLP-1 receptor agonists (such as semaglutide, tirzepatide) offer even greater weight reduction but their use in breast cancer survivors is still under study. In one small cohort on aromatase inhibitors, women lost significantly less weight on GLP-1 receptor agonists than matched controls, hinting that estrogen suppression might blunt satiety signaling; whether tamoxifen exerts a similar effect is unclear. ¹

Limited evidence to date suggests that GLP-1 receptor agonists do not increase breast cancer recurrence or worsen outcomes. Most available human data are observational or retrospective, derived from small cohorts with relatively short follow-up, so conclusions remain provisional. Preclinical studies are mixed: some in vitro and animal models show that GLP-1 agonists may inhibit tumor growth or induce apoptosis, while others - particularly at high doses or in specific models - raise the possibility of tumor promotion. Large real-world diabetic cohort analyses generally do not indicate increased breast cancer incidence with GLP-1 therapy, and some suggest a potential reduction in obesity-related cancer risk. Overall, the current evidence is limited and preliminary, underscoring the need for prospective trials to clarify long-term effects on disease-free survival and recurrence.^2,7,8

Safety considerations are also relevant when prescribing GLP-1 receptor agonists in cancer survivors. The most frequently reported adverse effects are gastrointestinal and include nausea, vomiting, diarrhea, and early satiety, particularly during dose escalation. These effects are generally mild and transient but may limit tolerability in some patients. GLP-1 receptor agonists have also been associated with an increased risk of gallbladder disease, likely related to rapid weight loss and altered biliary motility. Early post-marketing reports raised concerns regarding pancreatitis; however, large randomized trials and meta-analyses have not demonstrated a consistent increase in pancreatitis or pancreatic cancer risk, although caution is advised in individuals with a prior history of pancreatitis. Additionally, rodent studies demonstrated an increased incidence of thyroid C-cell tumors with GLP-1 receptor agonists, leading to contraindications in patients with medullary thyroid carcinoma or multiple endocrine neoplasia type 2, although this association has not been confirmed in humans. In clinical practice, patients receiving GLP-1 receptor agonists should undergo routine metabolic and oncologic follow-up according to standard breast cancer survivorship guidelines, with additional clinical monitoring for gastrointestinal intolerance, symptoms of gallbladder disease, or signs suggestive of pancreatitis.^8,9

Current evidence regarding GLP-1 receptor agonists in breast cancer survivors is limited to isolated case reports and retrospective studies, with little data specifically addressing tamoxifen-associated metabolic dysfunction.^1,6-10 Crowley et al (Front. Oncol. 2024) reported a single case of a 61-year-old woman who had gained significant weight and developed severe lymphedema during breast cancer treatment (chemotherapy and hormone therapy). She began a GLP-1 receptor agonist (type not specified) for weight loss and over 13 months lost ∼24% of her body weight. Her lymphedema markedly improved (limb volume difference fell, compression no longer needed). The patient remained on adjuvant endocrine therapy throughout. No adverse interactions were noted. This report highlights an extraordinary response to a GLP-1 receptor agonist in the context of endocrine therapy. ⁶ No other published case report or small case series specifically examining weight loss from GLP-1 receptor agonists in breast cancer survivors was found in peer-reviewed journals. (Several conference abstracts have appeared, but we excluded non–peer-reviewed material.)

The three retrospective cohort studies provide larger-scale evidence regarding the use of GLP-1 receptor agonists in breast cancer survivors. Shen et al (Oncology, 2025) evaluated breast cancer patients treated with GLP-1 receptor agonists at a single center for diabetes management or weight reduction. The study found modest weight loss during treatment. Approximately half of the patients were receiving concurrent endocrine therapy, which was associated with slightly less weight reduction, although the difference was not statistically significant. Importantly, GLP-1 receptor agonists were well tolerated, and endocrine therapies such as tamoxifen or aromatase inhibitors were continued safely without reported drug interactions. ¹ Sukumar et al (Cancer Res Commun, 2026) performed a large retrospective analysis of non-metastatic breast cancer survivors and reported modest weight loss with GLP-1 receptor agonist therapy. Concurrent endocrine therapy appeared to attenuate the weight-loss effect, whereas concomitant metformin use correlated with greater weight reduction. In matched analyses, GLP-1 receptor agonist use was not associated with worse oncologic outcomes and was linked to improved overall survival — an observational finding that may reflect residual confounding. ⁷ Brown et al (Frontiers in Oncology, 2024) conducted a retrospective analysis of women undergoing axillary lymph node dissection for breast cancer and found that GLP-1 receptor agonist use was associated with a significantly lower incidence of lymphedema. Although weight change was not directly reported, patients receiving GLP-1 receptor agonists had a high baseline BMI, suggesting underlying obesity. The findings indicate a potential secondary benefit of GLP-1 receptor agonists in reducing lymphedema risk, with no safety concerns reported. ¹⁰ The above cohort studies consistently indicate that GLP-1 receptor agonists yield modest weight loss in breast cancer patients, on the order of a few percent of body weight. These reductions, though smaller than the 8–15% seen in general obesity trials, are comparable to the ∼5% losses achieved in intensive behavioral programs for survivors. Importantly, weight loss was observed even in women continuing endocrine therapy.^1,7,10

Our case illustrates that liraglutide may help reverse substantial weight gain occurring during tamoxifen therapy and metabolic derangement, allowing continuation of adjuvant endocrine therapy with improved patient well-being. This outcome is consistent with emerging evidence that GLP-1 receptor agonists (including liraglutide) produce clinically meaningful weight loss in breast cancer survivors. ⁶ To date, very few cases of this scenario have been reported, emphasizing the novelty of our experience. Nevertheless, growing observational data support further study: formal trials are needed to determine optimal dosing and long-term effects of GLP-1 receptor agonists use specifically for endocrine therapy–related obesity. In the meantime, clinicians should recognize that pharmacologic weight loss therapy – as exemplified here – may be a safe and effective adjunct when lifestyle measures alone are insufficient for tamoxifen-treated survivors.^1,6

The novelty of our case lies in the comprehensive documentation of marked reversal of tamoxifen-associated metabolic dysfunction during uninterrupted endocrine therapy. Although GLP-1 receptor agonists are increasingly used in breast cancer survivors, published evidence remains limited to isolated case reports and retrospective studies demonstrating modest average weight loss, with limited data on normalization of insulin resistance and other metabolic abnormalities. Our case documents substantial weight reduction accompanied by normalization of HOMA-IR, HbA1c, and lipid profile, thereby expanding the available evidence on the metabolic benefits of GLP-1 receptor agonists in this clinical setting.^1,6-8

These findings further support the recognition of tamoxifen-associated weight gain as an important survivorship challenge that requires structured, multidisciplinary metabolic management rather than reliance on lifestyle advice alone. Recent evidence indicates that dietary restriction, with or without physical activity interventions, can induce weight reduction in breast cancer survivors; however, improvements in cardiometabolic outcomes remain variable and are often difficult to sustain. ¹¹ Similarly, a Cochrane systematic review concluded that weight-management interventions in overweight or obese breast cancer survivors can improve body weight, body mass index, and waist circumference, while emphasizing the need for standardized and adequately powered approaches. Furthermore, retrospective evidence suggests that multidisciplinary weight-management programs incorporating endocrinology, nutritional counseling, and exercise support may improve weight and body composition outcomes, highlighting the potential value of integrating metabolic care into breast cancer survivorship pathways.^12,13

Limitations

This case report has several limitations. First, it describes a single patient, limiting the generalizability of the findings. Second, the observational nature and absence of a comparator prevent establishing a causal relationship between liraglutide and the observed weight loss and metabolic improvements. Third, follow-up after liraglutide initiation was limited to 12 months, so the long-term durability of these effects and oncologic safety cannot be determined. Finally, unmeasured lifestyle or individual factors may have contributed to the observed response. Further prospective studies with larger samples and longer follow-up are needed.

Conclusion

This case describes substantial weight reduction and improvement in metabolic parameters in a breast cancer survivor receiving tamoxifen after initiation of liraglutide therapy, following unsuccessful lifestyle interventions. The degree of weight loss observed was greater than that reported in some observational studies of GLP-1 receptor agonists in breast cancer populations; however, responses to therapy may vary widely among individuals. Because this report reflects the experience of a single patient, no conclusions regarding efficacy or causality can be drawn. Nevertheless, the case highlights the potential role of GLP-1 receptor agonists as a therapeutic option that warrants further investigation for managing endocrine therapy–associated weight gain. Prospective studies are needed to better define their safety, effectiveness, and role within breast cancer survivorship care.

ORCID iD

Mohammad Adi https://orcid.org/0000-0003-0386-6742

Ethical Considerations

Ethical approval was not required for this case report, as it involves a single patient and does not meet the criteria for research requiring institutional review board (IRB) oversight. The use of authorized medications was consistent with clinical practice guidelines, and the management of this individual patient did not require IRB approval.

Consent for Publication

Written informed consent was obtained from the patient prior to publication of this case report and any accompanying images. The completed consent form is available to the Editor upon request and will be treated confidentially.

Data Availability Statement

All data pertinent to this case report have been included in this article. Further inquiries can be directed to the corresponding author.*