Metabolic and nutritional stress-associated dilated cardiomyopathy in the setting of semaglutide use and long-term nicotine replacement therapy: a case report and literature review

Abstract

Dilated cardiomyopathy (DCM) is a leading cause of heart failure and cardiac transplantation worldwide. It is a multifactorial condition with diverse aetiologies, in which metabolic and nutritional factors are increasingly recognised, whereas pharmacological contributors remain comparatively underexplored. We describe a 57-year-old man presenting with acute heart failure and cardiogenic shock after a 12-h prodrome of chest pain and dyspnoea. He had intentionally lost 26 kg over 2 months through 0.25 mg semaglutide therapy, and reports >25 years of chronic nicotine replacement therapy (NRT: 30–40 mg/day). Evaluation showed global left ventricular systolic dysfunction with an ejection fraction of 15%, marked dilation, moderate mitral regurgitation and right ventricular insertion-point fibrosis. Coronary angiography and an extensive cardiomyopathy work-up were unremarkable. This case highlights the potential for severe myocardial dysfunction in the setting of profound metabolic and nutritional stress, including rapid weight loss, sustained caloric restriction and high-intensity exercise. Pharmacological exposures, such as glucagon-like peptide-1 agonists and chronic NRT, may have contributed indirectly by facilitating prolonged energy imbalance rather than acting as direct cardiotoxic agents. Evidence directly linking either exposure to DCM remains limited, underscoring the need for further clinical research. This report suggests that the myocardium may be vulnerable to significant energy deficit and nutritional depletion, particularly in the context of pharmacologically facilitated weight-loss behaviours.

Plain language summary

More than meets the eye: how rapid weight loss and nutritional stress – potentially linked to semaglutide and nicotine gum – may affect heart health

This case report describes a man who developed severe weakening of the heart muscle, known as dilated cardiomyopathy, in whom no clear cause could be identified after medical assessment. Two features of his history stood out: very rapid weight loss and severe caloric restriction of 750 kcal/day while taking semaglutide, and long-term use of high-dose nicotine replacement therapy for over 25 years. An extensive assessment for possible causes was performed; however, genetic testing was not undertaken due to cost, meaning not all causes could be fully excluded.

This report explores how severe stress from rapid weight loss and poor nutrition may have contributed to this patient’s heart condition, and considers how semaglutide and nicotine gum may have indirectly played a role. Semaglutide can reduce appetite, which in some cases may lead to people eating too little over time. While weight loss can be beneficial, when it results in poor nutritional intake, it can affect the normal function of the heart.

Nicotine gum is commonly used as a safer alternative to smoking and is generally considered low risk. However, long-term nicotine exposure may still have effects on the heart and circulation. In this case, it is biologically plausible that it acted as an additional contributing factor alongside the metabolic and nutritional stress from severely low caloric intake. Although this case demonstrates the impact of severe malnutrition on the heart, it also examines how both medications may have indirectly contributed to the patient’s overall deterioration.

Keywords

case report dilated cardiomyopathy glucagon-like peptide-1 agonist nicotine semaglutide

Introduction

Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality globally.¹ DCM is a common cause of heart failure and the most common indication for cardiac transplantation worldwide, with a prevalence of approximately 40 cases per 100,000.² The prognosis remains poor, with a 5-year mortality of 20%–30% in patients with an ejection fraction (EF) <35%.³ The condition is associated with many causes, including genetic mutations, infection, autoimmune conditions, toxins and endocrinopathies⁴; however, many cases remain idiopathic. This rise raises the question of whether previously unrecognised environmental factors contribute to its pathogenesis.⁵

Clinicians have previously hypothesised rapid weight loss as an aetiology for DCM, due to the significant stress placed on the myocardium from severe caloric restriction and nutritional deficiencies. Multiple observational and murine studies have shown reproducible alterations in cardiac function.^6,7 In an era where pharmacological therapies for weight reduction are becoming readily available,⁷ achieving rapid weight loss has never been more attainable. Glucagon-like peptide-1 (GLP-1) agonists are an increasingly utilised pharmacological intervention for weight reduction worldwide. There were almost 2.4 million semaglutide prescriptions in Australia in 2023–2024, costing roughly $285 million Australian dollars.⁸ GLP-1 agonists enhance glucose-dependent insulin secretion, reducing inappropriate glucagon release, slowing gastric emptying and promoting early satiety.⁷ These mechanisms contribute to sustainable weight loss, as evidenced by several clinical trials.^9,10 Recent evidence shows GLP-1 agonists receive unusually high levels of promotional attention across major social media platforms, reflecting unprecedented public enthusiasm for these agents.¹¹ Given its potent appetite-suppressing effects, this raises the possibility that an increasing number of individuals may develop nutritional deficiencies due to sustained severe caloric restriction facilitated by GLP-1 agonists.

Chronic nicotine replacement therapy (NRT) also merits thorough investigation in the context of DCM. Nicotine’s link to coronary artery disease and hypertension is well established.¹² It increases myocardial oxygen demand through enhanced sympathetic activity, leading to coronary vasoconstriction and increased chronotropy and inotropy.¹² However, this is in the presence of other chemicals in cigarettes.¹³ The cardiovascular implications of chronic pure nicotine exposure, such as that from medicinal NRTs, are not fully elucidated.¹³ While guidelines vary, the prevailing consensus advocates limiting NRT to a maximum of 12 months, as there is no evidence of efficacy beyond 24 weeks.¹⁴ The safety of long-term NRT remains poorly characterised. The most notable clinical trial, published in the New England Journal of Medicine, reported no adverse outcomes with transdermal nicotine use over 14 weeks,¹⁵ a duration that does not reflect the decades-long exposure seen in patients such as ours. Existing studies are further limited by inadequate consideration of how different delivery systems influence nicotine absorption and metabolism. NRTs typically produce slower, lower and more sustained plasma nicotine concentrations than the rapid peaks associated with tobacco smoking or e-cigarette use.^16,17 As a result, some individuals escalate dosing to achieve desired psychoactive effects, potentially leading to prolonged high systemic nicotine levels that may induce adverse cardiovascular remodelling and dysfunction through increased myocardial demand.¹²

In this case report and literature review, we describe a presentation of DCM most consistent with metabolic and nutritional stress. Rapid weight loss driven by severe caloric restriction and intense exercise – facilitated by semaglutide-associated appetite suppression – may have contributed to this process. In addition, chronic high-dose nicotine exposure may have further increased myocardial vulnerability during periods of heightened metabolic and nutritional stress. A narrative literature review was conducted examining the cardiovascular effects of rapid weight loss and nutritional deficiency in the context of semaglutide use, as well as the potential association between chronic NRT and DCM. While several case reports and literature reviews have explained the impact of metabolic stress and nutritional deficiencies on myocardial dysfunction, none to our knowledge have explored the potential contributions of these two pharmacological factors in this context.

Case presentation

We report a 57-year-old man presenting with 12 h of heavy left-sided chest pain radiating to the left arm, accompanied by worsening dyspnoea, but no presyncope or palpitations. He had been well prior and denied previous chest pain. His history included gout treated with colchicine as needed, a 20–pack-year smoking history and no alcohol use. The patient had no cardiac risk factors and no family history of cardiac disease or sudden cardiac death. Since quitting smoking 25 years earlier, he had consumed 30–40 mg of nicotine gum daily. He also reported a 26-kg intentional weight loss over 2 months achieved through a 750-kcal/day diet, weekly semaglutide 0.25 mg and daily 2-h high-intensity exercise. Prior to admission, the patient had been using semaglutide for approximately 2 months, prescribed on a private script by his general practitioner for weight management. During this period, the dose remained at 0.25 mg weekly and was not escalated. This was primarily due to the patient’s substantial weight loss early in therapy, as well as the financial cost associated with the medication, leading both the patient and prescriber to defer dose escalation.

On arrival, the patient’s body mass index (BMI) was 26, he was tachycardic at 113 bpm, and hypotensive at 83/63 mmHg. Examination revealed bi-basal crepitations, bilateral pedal oedema, but no oxygen requirement. An electrocardiogram (ECG) demonstrated sinus rhythm with new lateral T-wave inversion, frequent premature ventricular complexes and a new prolonged QTc of 460 ms (Figure 1). Troponin was 457 ng/L, rising to 519 ng/L when repeated 2 h later. Laboratory results showed a normocytic anaemia (haemoglobin (Hb) 126 g/L), hypoalbuminaemia (32 g/L), hypomagnesaemia (0.47 mmol/L) and a brain natriuretic peptide of 662 ng/L. CT pulmonary angiography excluded pulmonary embolism but demonstrated evidence of acute pulmonary oedema (APO). Given his haemodynamic instability, he was urgently transferred for coronary angiography.

The angiogram demonstrated normal epicardial coronaries and an elevated left ventricular (LV) end-diastolic pressure of 20 mmHg. The procedure was terminated before a left ventriculogram could be performed, as the patient acutely deteriorated and developed a new oxygen requirement of 4 L/min. He was transferred to the ward and placed on telemetry. A formal transthoracic echocardiogram (TTE) was limited by patient positioning but showed an EF of 15% with global systolic dysfunction and moderate mitral regurgitation; the right ventricle was mildly dilated with preserved function, and no pericardial effusion was present (Figure 2). An evaluation for cardiomyopathy – including iron studies, thyroid function tests, free light chains, viral panel, and testing for legionella and chlamydia – was unremarkable. Screening for micronutrient deficiencies (copper, selenium, zinc, vitamin B6 and thiamine diphosphate) was also normal. Cardiac magnetic resonance imaging (MRI) confirmed severe LV dilation, a severely reduced EF of 17%, moderate functional mitral regurgitation and fibrosis at the RV insertion point, without evidence of infiltrative disease (Figure 3).

Although the aetiology remained unclear, the patient was treated with intravenous (IV) meropenem for possible atypical infection and 80 mg IV furosemide daily for APO. As his blood pressure improved, low-dose bisoprolol 2.5 mg was introduced; however, he subsequently deteriorated with worsening bradycardia, requiring an intensive care unit (ICU) admission for a dobutamine infusion and vasopressor support. The patient was closely monitored in the ICU, and once end-organ function and haemodynamics stabilised, he was discharged to the cardiac ward. The patient had heart failure therapy slowly introduced, commencing with ramipril 2.5 mg, followed by ivabradine 5 mg twice daily and dapagliflozin 10 mg daily. After several days of haemodynamic stability and symptom resolution, he was discharged home, having spent 15 days in hospital, including three in ICU, with no definitive cause identified.

The patient was followed up in the clinic 2 months later, with a repeat TTE demonstrating an EF of 20%, and persistent global systolic dysfunction. Genetic testing for cardiomyopathy was offered, but in the absence of a family history of cardiac disease, it was not government subsidised and therefore declined due to cost. Despite no improvement in EF, he reports a gradual return to daily activities without heart failure symptoms. He also reports tolerating his new medications well, with no adverse effects and good adherence to therapy. He remains under cardiology follow-up for chronic heart failure management, with consideration of cardiac resynchronisation therapy if his EF remains low at his 6-month review. A timeline of events from the initial presentation to the 2-month follow-up is summarised in Figure 4. Written consent was obtained from the patient for publication of his case and all relevant images.

Method

A narrative literature review was undertaken to explore two potential mechanisms discussed in this case: (1) cardiomyopathy associated with rapid or severe weight loss and metabolic stress and (2) potential cardiovascular effects of semaglutide and nicotine exposure. Searches were performed in PubMed, Scopus and Embase using combinations of keywords and Medical Subject Headings including ‘rapid weight loss’, ‘GLP-1 receptor agonist’, ‘semaglutide’, ‘nicotine’, ‘nicotine replacement therapy’ and ‘dilated cardiomyopathy’. Google Scholar was additionally used to identify potentially relevant grey literature and recently published studies.

Relevant articles were identified through title and abstract screening, followed by full-text review of selected papers. Given the exploratory nature of the review and the limited literature directly addressing the proposed mechanisms, formal inclusion and exclusion criteria were not applied. Instead, studies were selected based on their relevance to the proposed pathophysiological mechanisms and their contribution to understanding potential links between rapid weight loss, metabolic stress, nicotine exposure, GLP-1 agonists and myocardial dysfunction. Study selection and interpretation of the literature were performed collaboratively by the authors through discussion and consensus to ensure a balanced appraisal of the available evidence. This case report was prepared in accordance with the CARE guidelines (Supplemental Material).¹⁸

Discussion

Metabolic/nutritional stress cardiomyopathy facilitated by GLP-1 therapy

Rapid weight loss and malnutrition as a potential cause of cardiomyopathy

Weight loss is fundamental in managing many chronic conditions, and contemporary pharmacotherapies – particularly GLP-1 receptor agonists – highlight the benefits of structured, intentional weight reduction. However, the assumption that all weight loss is uniformly advantageous is not supported across clinical contexts. In heart failure with reduced ejection fraction (HFrEF), unintentional weight loss is a well-established adverse prognostic marker.¹⁹ Anker et al. showed that a ⩾7.5% reduction in non-oedematous body weight independently predicted increased mortality in HFrEF,¹⁹ a finding consistently reaffirmed in large cohorts. Post hoc analyses of SOLVD demonstrated that progressive weight loss worsened outcomes irrespective of baseline status or ACE-inhibitor use,²⁰ while CHARM confirmed that ongoing weight loss strongly predicted all-cause and cardiovascular mortality.²¹ Conversely, the obesity paradox – where higher BMI is associated with improved survival – has been repeatedly observed, with overweight and mildly obese patients exhibiting lower mortality than those with normal BMI.²² Mechanistic reviews attribute this paradox to factors such as greater metabolic reserve, reduced neurohormonal activation and protective adipokine signalling.²³

Furthermore, it is important to consider how such substantial weight reductions can affect myocardial structure and function. Weight loss can reduce myocardial mass, and studies examining this phenomenon have indeed demonstrated declines in myocardial mass over time.²⁴ However, these investigations have focused on gradual, medically supervised weight reduction and consistently shown improvements in cardiac function.²⁴ A systematic review and meta-analysis of bariatric surgery similarly reported reductions in LV mass at 12 months,²⁵ accompanied by improved systolic function,²⁵ but again did not reflect the rapid weight loss observed in our patient. Nevertheless, the review offers a plausible physiological basis for myocardial mass reduction with weight loss.²⁵ Comparable findings have been reported in anorexia nervosa, where one study demonstrated a 30%–50% reduction in LV mass,²⁶ a change implicated in the development of mitral valve prolapse in this cohort.²⁷

The patient’s extreme weight loss over a short period also raises concern for inadequate caloric and micronutrient intake. Although this patient’s micronutrient screen was normal, early deficits – particularly with a severe caloric restriction of 750 kcal/day – may precede laboratory detection. Nutritional deficiency is a recognised cause of cardiomyopathy, with thiamine-deficient beriberi the classical example.²⁸ Early descriptions distinguished the high-output failure of classical beriberi from shoshin beriberi, a fulminant variant marked by circulatory collapse and lactic acidosis, rapidly fatal without thiamine repletion.^29
–34 Deficiencies of other nutrients, notably selenium and phosphate, likewise produce profound myocardial dysfunction.^35
–39 Selenium deficiency underlies Keshan disease and occurs in patients on parenteral nutrition or restrictive diets,^35
–38 while hypophosphataemia – seen in refeeding and anorexia nervosa – impairs contractility and may precipitate acute decompensation.^40
–43 Beyond isolated deficiencies, severe malnutrition is closely linked to structural and electrophysiological cardiac abnormalities. Starvation in World War II prisoners was associated with bradycardia, exertional tachyarrhythmias, QT prolongation and sudden death, and necropsy revealed small, flabby, atrophic hearts.^44
–47 Additional reports across diverse settings support this association. Apartheid-era case series described a nutritional cardiomyopathy distinct from beriberi – unresponsive to thiamine yet reversible with adequate caloric and protein intake.^48
–50 In children with kwashiorkor – a severe protein-deficiency syndrome – QT prolongation, ventricular dilatation and myocardial fibre loss were frequently observed.^51,52 Electrolyte derangements from very low-calorie regimens are well recognised to increase the risk of ventricular arrhythmias,^53,54 and our patient’s hypomagnesaemia, tachycardia, ventricular ectopy and prolonged QTc collectively indicate membrane instability. Takotsubo cardiomyopathy – a catecholamine-driven myocardial injury – was also considered.⁵⁵ Pissaia et al. showed that severe protein malnutrition in rats induced acute catecholamine surges with corresponding pathological ECG changes.⁵⁶ In this patient, extreme caloric restriction combined with excessive exercise could plausibly have produced sustained catecholamine elevation, precipitating Takotsubo cardiomyopathy.

GLP-1 receptor agonists and cardiomyopathy

GLP-1 receptor agonists are established pharmacological therapies for weight management and are increasingly prescribed worldwide, including beyond their original indication for type 2 diabetes mellitus. These agents improve glycaemic control through glucose-dependent insulin secretion, suppression of glucagon release and delayed gastric emptying while also promoting weight loss through appetite suppression and enhanced satiety.⁵⁷ The efficacy of GLP-1 receptor agonists for weight reduction has been demonstrated in large randomised controlled trials, including the Semaglutide Treatment Effect in People with Obesity (STEP) program, which reported substantial reductions in body weight among patients receiving semaglutide.^58,59 Similar findings have been observed with other GLP-1 receptor agonists, including liraglutide in the SCALE trial and dulaglutide in the AWARD-11 trial.^60,61 In STEP-8, semaglutide therapy resulted in a mean weight reduction of 15.8% over 68 weeks,⁶² and one systematic review and meta-analysis reported an average weight loss of 11.85% over a similar timeframe.⁶³ By contrast, our patient experienced a 21.6% reduction in body weight over only 2 months. This unusually rapid weight loss may reflect a combination of severe caloric restriction facilitated by GLP-1–mediated appetite suppression and excessive exercise, resulting in a pronounced catabolic state that may precipitate muscle loss and nutritional deficiencies. Emerging evidence suggests that GLP-1 therapy may be associated with nutritional deficiencies through its appetite-suppressing effects; a large retrospective cohort study of nearly 500,000 adults reported nutritional deficiencies in over 20% of patients within 1 year of treatment initiation.⁶⁴ In addition, case reports have described severe complications, including thiamine deficiency, starvation ketoacidosis and profound hypomagnesaemia, in patients receiving incretin-based therapies.^65,66

Interestingly, there is also emerging evidence for the use of GLP-1 agonists in heart failure with preserved ejection fraction (HFpEF).⁶⁷ The STEP-HFpEF and STEP-HFpEF DM trials demonstrated a significant improvement in heart failure symptoms for patients taking semaglutide.⁶⁸ Furthermore, a prespecified analysis of the SELECT trial evaluated semaglutide in participants with heart failure – predominantly HFpEF – and demonstrated clinically meaningful reductions in major adverse cardiovascular events.^69,70 These benefits were observed despite only modest weight reduction within the trial population, with participants achieving a mean loss of approximately 9.8 kg during the first year of treatment. Importantly, the gradual weight loss seen in SELECT differs substantially from the extreme and rapid caloric deficit experienced by our patient.⁷¹ This distinction highlights that while GLP-1–mediated weight loss may be beneficial in HFpEF, excessively rapid weight loss accompanied by nutritional insufficiency – potentially facilitated by appetite suppression from GLP-1 therapy – may precipitate adverse myocardial consequences. Concerns regarding the cardiovascular safety of GLP-1 agonists have occasionally been raised, although the evidence remains limited. For example, liraglutide was associated with higher rates of cardiac adverse events in the LIVE study,⁷² and saxagliptin – a DPP-4 inhibitor which increases endogenous GLP-1 concentrations – was linked to increased heart failure hospitalisations in the SAVOR-TIMI-53 trial.⁷³ Despite this, there remains a paucity of evidence examining the direct effects of semaglutide on myocardial structure and function, making it difficult to conclude that the patient’s cardiomyopathy was attributable to a direct toxic effect of GLP-1 therapy. We propose that the profound caloric restriction facilitated by semaglutide’s appetite-suppressing effects possibly resulted in nutritional deficiencies that contributed to severe heart failure. This case underscores the myocardium’s susceptibility to nutritional insufficiency and highlights the potential for extreme caloric restriction – including that facilitated by GLP-1 agonists – to precipitate significant myocardial dysfunction.

Nicotine exposure and cardiomyopathy

Another feature warranting consideration was the patient’s 25-year history of persistent NRT use. While metabolic and nutritional stress is the most plausible primary driver, the history of prolonged high-dose nicotine exposure raises the question of whether it may have contributed to increased myocardial vulnerability to acute stressors. Nicotine acts via nicotinic acetylcholine receptors expressed in neuronal and non-neuronal tissues, including the cardiovascular system.⁷⁴ Its activation of dopaminergic reward pathways underpins dependence.⁷⁵ Emerging evidence indicates that prolonged NRT, independent of other tobacco toxins, may exert clinically relevant cardiovascular effects.¹² Preclinical studies implicate nicotine in endothelial dysfunction and altered myocardial contractility,⁷⁶ largely through suppression of endothelial nitric oxide synthase, reducing nitric oxide bioavailability, impairing vasodilation and promoting a pro-thrombotic, pro-inflammatory state.⁷⁶ Fang et al. showed that nicotine infusion markedly impaired NOS-dependent dilation of cerebral arterioles in rats,⁷⁷ and additional work confirms substantial reductions in nitric oxide bioavailability following nicotine administration.⁷⁸

Nicotine has also been implicated in cardiac remodelling.¹² In preclinical studies, Fried et al. demonstrated eccentric hypertrophy in rats chronically exposed to nicotine,⁷⁹ with proposed mechanisms involving heightened sympathetic activation and catecholamine release leading to sustained tachycardia and structural remodelling.⁸⁰ This pathophysiology also aligns with Takotsubo cardiomyopathy, where an acute-on-chronic catecholamine surge may precipitate deterioration.⁵⁵ Nicotine has further been shown to induce myocardial fibrosis and apoptosis,^80,81 raising the possibility that the right ventricular insertion-point fibrosis seen on our patient’s cardiac MRI – although often incidental – may reflect chronic exposure. Nicotine’s cardiovascular effects also extend to modulation of the renin–angiotensin system.⁸² The only human study addressing this indirectly, the LURIC study, found no significant differences in plasma renin or aldosterone between smokers and non-smokers,⁸³ though its interpretation is limited by heterogeneity in baseline characteristics and inadequate characterisation of smoking exposure.⁸⁴ By contrast, murine models consistently demonstrate increased renin, angiotensin II and aldosterone levels after nicotine exposure,^84,85 key mediators in heart failure pathophysiology.⁸⁵

Interestingly, nicotine use may also have influenced the patient’s haemodynamic response to beta-blockade. Although beta-blockers confer substantial long-term benefit in heart failure,^86,87 their negative inotropic and chronotropic effects can precipitate haemodynamic compromise or cardiogenic shock.^88,89 By contrast, nicotine exerts short-term sympathomimetic effects and has positive inotropic and chronotropic effects.^90,91 In our patient, it is plausible that the near-simultaneous cessation of self-administered nicotine and commencement of beta-blockade effectively removed this exogenous sympathetic stimulation at the same time that intrinsic adrenergic signalling was pharmacologically suppressed. This combination may have produced a decline in contractile reserve, plausibly contributing to the patient’s deterioration and subsequent ICU admission. Ultimately, while metabolic and nutritional stress represents the most plausible primary driver of the patient’s acute deterioration, chronic nicotine exposure may have played a contributory role by increasing myocardial vulnerability.

Limitations

This case report has several limitations. Firstly, a causality between the observed cardiomyopathy and suspected exposures cannot be definitively established. A causality assessment using the Naranjo Adverse Drug Reaction Probability Scale yielded scores within the ‘possible’ range for both semaglutide and chronic nicotine exposure (Table 1).⁹² The Naranjo Scale provides only supportive evidence in this case and has limited applicability in a multifactorial setting, where indirect and non-dose-dependent mechanisms – such as metabolic and nutritional stress – are likely to predominate.

Table 1.

Tabulated Adverse Drug Reaction Probability Scale (Naranjo) for semaglutide and nicotine.

Naranjo Question	Semaglutide	Score	Nicotine	Score
Previous conclusive reports	No	0	Limited evidence	0
Event after drug administration	Yes	+2	Chronic exposure present before event	+1
Improvement after discontinuation	Unknown	0	Unknown	0
Reappearance on re-challenge	Not performed	0	Not applicable	0
Alternative causes present	Yes (nutritional deficiency)	-1	Yes	-1
Placebo response	Not applicable	0	Not applicable	0
Drug levels toxic	No	0	No	0
Dose-response relationship	Not demonstrated	0	Not demonstrated	0
Previous similar reaction	No	0	No	0
Objective confirmation	Yes (TTE-confirmed DCM)	+1	Yes	+1

Causality between the suspected exposures (semaglutide and nicotine) and cardiomyopathy was assessed using the Naranjo Adverse Drug Reaction Probability Scale, a validated questionnaire-based tool used to estimate the likelihood that an adverse event is attributable to a drug. It is important to acknowledge that the Naranjo Scale provides only supportive evidence in this case and has limited applicability in a multifactorial context.

Additionally, while alternative causes of DCM were investigated, comprehensive genetic testing was not performed. Consequently, the possibility of an underlying genetic predisposition to cardiomyopathy cannot be entirely excluded. This is an inherent limitation in many single-case reports and highlights the need for cautious interpretation when attributing causality to pharmacologic or environmental exposures.

Conclusion

This case highlights the potential for severe myocardial dysfunction in the setting of profound metabolic and nutritional stress, including rapid weight loss, sustained caloric restriction and high-intensity exercise, which represents the most plausible underlying mechanism. Within this context, pharmacological exposures – including semaglutide and chronic NRT – may have contributed indirectly by facilitating sustained energy imbalance or increasing myocardial susceptibility to physiological stress, rather than acting as direct cardiotoxic agents. Evidence directly linking these agents to DCM remains limited, particularly in complex, multifactorial settings. Ultimately, this case underscores the importance of considering broader metabolic and nutritional consequences of extreme weight loss behaviours and highlights the need for further research into the potential indirect contributions by GLP-1 agonists and long-term NRT on cardiac function.

Supplemental Material

sj-docx-1-taw-10.1177_20420986261448034 – Supplemental material for Metabolic and nutritional stress-associated dilated cardiomyopathy in the setting of semaglutide use and long-term nicotine replacement therapy: a case report and literature review

Supplemental material, sj-docx-1-taw-10.1177_20420986261448034 for Metabolic and nutritional stress-associated dilated cardiomyopathy in the setting of semaglutide use and long-term nicotine replacement therapy: a case report and literature review by Siddarth Sriram and Leonard Arnolda in Therapeutic Advances in Drug Safety

Footnotes

Acknowledgements

The author acknowledges the use of JenniAI solely for assistance with academic writing and language refinement. All aspects of the literature review, and the accuracy and integrity of the final manuscript remain the full responsibility of the authors.

Declarations

ORCID iD

Dr. Siddarth Sriram

Supplemental material

Supplemental material for this article is available online.

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