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GLP-1 RAs in Substance Use Disorders: Emerging Evidence and Future Directions.
Cardiol Rev
Jason Macanian, William H Frishman
Substance use disorders (SUDs) are the leading causes of both global mortality and morbidity, and alcohol, nicotine, and opioids account for most of this burden. Existing pharmacotherapies are only moderately effective, have inconsistent compliance and regular relapse, and therefore, new treatment modalities are required. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), which have been licensed to treat type 2 diabetes and obesity, have emerged as potential therapeutic candidates for SUDs due to their central action on neural reward circuits. GLP-1 receptors are expressed in mesolimbic regions, and preclinical studies show decreases in drug use, suppression of nucleus accumbens efflux of dopamine, and inhibition of relapse-like behaviors in models of alcohol, nicotine, and opioids. Early clinical findings, particularly those from semaglutide, indicate reductions in both alcohol and cigarette consumption, although the results remain inconsistent and are limited by small sample size. Subgroup analysis and observational findings suggest that GLP-1RAs may have potentially larger effects in individuals with obesity and metabolic disease, which could also be due to metabolic modes of action. In opioid use disorder, evidence is currently limited to animal models but demonstrates comparable efficacy to established therapies. Collectively, GLP-1RAs represent an emerging and mechanistically novel therapeutic option for SUDs. Future research should prioritize large-scale randomized controlled trials, patient stratification, and long-term safety assessments to define their potential role as adjunct or standalone treatments in addiction medicine.
Atypical retrobulbar optic neuropathy after semaglutide escalation.
JCEM Case Rep
Shivaprasad Channabasappa, Riddhi Das Gupta, Vidhya Chandran +1 more
Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is widely used to manage type 2 diabetes and obesity. Recent pharmacovigilance signals have reported an increased incidence of nonarteritic anterior ischemic optic neuropathy (NAION) among semaglutide users, although the absolute risk remains low. We report a man in his early 30 seconds with class III obesity, obstructive sleep apnea, and prediabetes who developed acute, painless, asymmetric bilateral visual dysfunction four weeks after semaglutide escalation to 1 mg per week. Evaluation revealed retrobulbar optic neuropathy with asymmetric visual field defects, a central scotoma in the left eye, an altitudinal defect in the right eye, preserved optic disc appearance, and markedly delayed visual evoked potentials. Optical coherence tomography and neuroimaging were unremarkable. The presentation was atypical for NAION but did not fully align with classical demyelinating optic neuritis, yielding a mixed clinical picture. Semaglutide was discontinued immediately, and visual function remained stable over serial follow-up with adaptation to a persistent left central scotoma but no further deterioration. This case illustrates an atypical retrobulbar optic neuropathy in close temporal proximity to semaglutide dose escalation and underscores the need for clinical vigilance and strengthened pharmacovigilance as GLP-1RA use expands globally.
Mixed Medullary and Papillary Thyroid Carcinoma in a Patient on Tirzepatide.
Cureus
Lauren H Beshay, Jitin Makker, Susan Ahern
Medullary thyroid cancer (MTC) stems from thyroid parafollicular C cells and is considered a rare type of neuroendocrine tumor. It can be inherited as part of syndromes, such as familial medullary thyroid cancer (FMTC) and multiple endocrine neoplasia type 2 (MEN 2), or it can arise sporadically. GLP-1 receptor agonist drugs (GLP1 RA), like semaglutide and tirzepatide, carry an FDA black box warning against using them in patients who have a prior history or a family history of MTC or MEN2. This recommendation stems from rodent studies showing thyroid C-cell tumors. Current studies have not confirmed an association between GLP1RAs and risk of differentiated thyroid cancer in human studies. In addition, there is no consensus on screening or evaluating patients for thyroid cancer prior to or during treatment with GLP1 RA. Here, we report a case of mixed medullary and papillary thyroid carcinoma newly diagnosed in a 68-year-old female on tirzepatide for type 2 diabetes who presented with a neck mass.
Eating Disorders in the GLP-1 Era: A Spotlight on Emerging Clinical Risks, Research Gaps, and Practice Priorities.
Int J Eat Disord
Stjepan Škudar
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and related incretin-based medications are rapidly changing the treatment landscape for type 2 diabetes, obesity, cardiovascular risk reduction, and weight management. Their effects on appetite, satiety, gastrointestinal function, reward-related eating, and weight loss place them in direct contact with core psychological and behavioral domains of eating disorders. This Spotlight article argues that the eating disorders field urgently needs a coordinated clinical and research agenda for the GLP-1 era.
Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Thyroid Function Tests: A Systematic Review Identifying a Critical Evidence Gap.
Cureus
Sulafa Salama, Eltayeb Osman Elfaki Omer, Alaa Mahmoud +7 more
Glucagon-like peptide-1 (GLP-1) receptor agonists are widely used for type 2 diabetes and obesity management, yet their effects on thyroid function tests remain inadequately characterized. Preclinical rodent studies demonstrating C-cell hyperplasia have raised safety concerns, while clinical evidence regarding thyroid hormone dynamics is sparse and inconsistent. This systematic review aimed to synthesize available evidence on the effects of GLP-1 receptor agonists on thyroid function tests, explicitly acknowledging that direct evidence is limited and that characterizing this evidence gap is a primary objective. A comprehensive search of PubMed, Scopus, Web of Science, and ClinicalTrials.gov was conducted for studies published between January 2021 and December 2025. Eligible studies included randomized controlled trials and observational studies evaluating thyroid function parameters in adult patients receiving GLP-1 receptor agonists. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool for randomized trials and the Risk Of Bias In Non-randomized Studies of Interventions tool for observational studies. A narrative synthesis was performed due to substantial methodological heterogeneity precluding meta-analysis. Six studies encompassing 900,225 participants met the inclusion criteria, including three randomized controlled trials, two retrospective cohort studies, and one combined Mendelian randomization and cohort study. Only one study directly assessed thyroid function tests, reporting a mild decrease in free thyroxine and slight thyroid nodule progression after 12 months of therapy, though Mendelian randomization analysis revealed no significant causal effect. The remaining five studies did not systematically evaluate thyroid function parameters, focusing instead on thyroid malignancy outcomes or weight loss efficacy. The large-scale cohort studies demonstrated no increased risk of thyroid tumors or thyroid cancer with GLP-1 receptor agonist use. Risk of bias was low for two observational studies and moderate for one due to potential residual confounding, while two randomized trials demonstrated low risk of bias and one raised some concerns regarding outcome measurement. This systematic review aims to critically evaluate the available evidence - and, more explicitly, to characterize the substantial evidence gap - concerning the effects of GLP-1 receptor agonists on thyroid function tests. While only one of six included studies directly addressed this outcome, and available data suggest no increased thyroid malignancy risk, definitive conclusions regarding functional thyroid effects cannot be drawn due to the absence of systematic thyroid function assessments in most included studies, particularly the major randomized controlled trials. Future research should incorporate systematic thyroid hormone monitoring to clarify the clinical significance of GLP-1 receptor agonist therapy on thyroid axis regulation.
Combining GLP-1 Receptor Agonists and Health-Behaviour and Lifestyle Therapy Yields Higher Adherence and Reduces Session Needs for Successful Weight Management in Adolescence: An Observational Real-World Single-Center Study.
Pediatr Obes
Julia Lischka, Gabriel Torbahn, Michael Vallis +15 more
Evidence for the role of health behaviour and lifestyle treatment (HBLT) on the effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in paediatric obesity is limited.
A Review of the Oral Semaglutide in Adults with Overweight or Obesity (OASIS) Trials Evaluating Oral Semaglutide (Wegovy) for Chronic Weight Management in Adults With Overweight or Obesity.
Cureus
Blessing T Ojinna, Sara Tariq, Osamede Agho +2 more
Obesity is an increasingly growing public health issue affecting a substantial proportion of the population in the United States. This condition increases the risk for multiple disease processes, including cardiometabolic disorders, osteoarthritis, gout, respiratory issues, reproductive problems, and some cancers. Glucagon-like peptide-1 (GLP-1) receptor agonists got their first US Food and Drug Administration (FDA) approval in 2005 in the form of exenatide for type 2 diabetes mellitus (T2DM) management. Thereafter, GLP-1 analogs have been increasingly studied as a noninvasive strategy for weight reduction, and they transitioned from diabetes-only therapies to weight management with the approval of once-daily liraglutide prior to weekly semaglutide formulation in 2021. In essence, GLP-1 receptor agonists have emerged as a promising drug for long-lasting weight reduction and blood glucose control for patients with or without type 2 diabetes mellitus, surpassing traditional methods such as lifestyle changes and bariatric surgery. Oral Wegovy (Rybelsus) was approved for T2DM management in 2020; however, it is approved for weight loss after the recent publication of Oral Semaglutide in Adults with Overweight or Obesity (OASIS). This literature review will discuss and summarize weight loss results from OASIS trials 1, 2, 3, and 4. The OASIS 1 and 2 trials compared the therapeutic efficacy and clinical safety profile of once-daily oral semaglutide 50 mg versus placebo on overweight and obese participants without T2DM and both with and without T2DM, respectively. The OASIS 3 trial assessed the therapeutic efficacy and clinical safety profile of once-daily oral semaglutide 50 mg versus placebo in 200 Chinese adults who were obese and overweight with one or more weight-related comorbidities, including T2DM. The OASIS 4 trial evaluated the safety and effectiveness of once-daily semaglutide 25 mg in obese and overweight patients without T2DM. Clinical trial data and relevant literature were retrieved through database searches of the National Center for Biotechnology Information and ClinicalTrials.gov. The OASIS 1, 2, and 4 demonstrated that oral semaglutide has superior efficacy compared to placebo in body weight loss, which helped secure FDA approval for oral Wegovy. Though OASIS 3 is registered in clinical trials, the results of OASIS 3 have not been published in a peer-reviewed journal yet.
Influence of an AQP4 haplotype and sleep duration on early Alzheimer's disease.
Alzheimers Dement
Emma L Palatsides, Stephanie Yiallourou, Dibya Himali +14 more
Aquaporin-4 (AQP4) is thought to facilitate Alzheimer's disease (AD) protein clearance during sleep. We examined whether AQP4 genetic variation was associated with AD pathology or modified the association between sleep duration and AD biomarkers.
Total NT-proBNP in heart failure with preserved vs reduced ejection fraction.
Int J Cardiol
Camilla Hage, Anika Mang, Jean Claude Daubert +4 more
Commercially available NT-proBNP assays can underestimate concentration as the detecting antibody binds to NT-proBNP glycosylated epitopes, thereby underestimating the total NT-proBNP, impairing diagnostic and prognostic performance in heart failure (HF) patients.
Red blood cell distribution width for prediction of new-onset heart failure in the general population.
Int J Cardiol
Daniëlle J Noordermeer, Frank van Rooij, Maryam Kavousi +1 more
Red blood cell distribution width (RDW), a routine and inexpensive blood parameter, is widely available and may serve as a useful screening marker for heart failure (HF). This study aims to evaluate RDW's predictive value for new-onset HF in the general population and examine its incremental predictive performance alongside NT-proBNP.
Severe Arrhythmia Complicating Takotsubo Cardiomyopathy Revealing an Underlying Pheochromocytoma: A Case Report.
Cureus
Meryem Tabat, Zineb El Jaouhari, Abdnacer Drighil
Pheochromocytoma is a rare catecholamine-secreting tumor that can cause major cardiovascular complications, including acute heart failure, arrhythmias, and stress-induced cardiomyopathy. Takotsubo syndrome (TTS) is an acute non-ischemic cardiomyopathy characterized by transient left ventricular systolic dysfunction without obstructive coronary artery disease, often mimicking acute coronary syndrome. Catecholamine excess plays a central role in its pathophysiology, leading to myocardial stunning, hemodynamic instability, and arrhythmias. The association between pheochromocytoma and TTS is uncommon and frequently associated with severe clinical presentations. We report the case of a 52-year-old woman with poorly controlled hypertension treated with a calcium channel blocker, who presented with chest pain, dyspnea, and palpitations. On admission, blood pressure was 178/122 mmHg, and heart rate was 102 bpm. The patient described recurrent episodes of headache and palpitations occurring two to three times monthly and lasting 30 to 60 minutes, suggesting secondary hypertension. Electrocardiography showed 1 mm ST-segment elevation in the anterior leads without reciprocal changes and a prolonged QTc interval (480 ms). Peak high-sensitivity troponin reached 1880 ng/L (reference <35 ng/L), while brain natriuretic peptide (BNP) was 450 pg/mL (reference <125 pg/mL). Transthoracic echocardiography revealed a left ventricular ejection fraction of 45% with apical akinesia and basal hyperkinesia, consistent with Takotsubo syndrome. Left ventriculography confirmed typical apical ballooning, and coronary angiography showed no obstructive coronary artery disease. During hospitalization, the patient developed rapid atrial fibrillation with hemodynamic instability, requiring electrical cardioversion and amiodarone therapy. Labile blood pressure and paroxysmal symptoms raised suspicion of catecholamine excess, subsequently confirmed by elevated plasma and urinary metanephrines. Abdominal CT identified a 30 × 25 × 28 mm left adrenal mass with attenuation >10 HU and intense heterogeneous contrast enhancement, highly suggestive of pheochromocytoma. Preoperative treatment with phenoxybenzamine was progressively titrated to achieve hemodynamic stabilization before surgical resection. After surgery, left ventricular systolic function completely recovered, with ejection fraction improving to 58%. At the sixth-week follow-up, plasma and urinary metanephrines had normalized, confirming complete biochemical remission and successful tumor removal. Blood pressure also normalized postoperatively. This case highlights the importance of considering pheochromocytoma in patients with Takotsubo syndrome complicated by severe arrhythmias or labile hypertension, as early diagnosis may improve management and prognosis.
Axis-Specific Peripartum Management for Radiation-Induced Panhypopituitarism With Arginine Vasopressin Deficiency: A Case Report.
AACE Endocrinol Diabetes
Takashi Kono, Hiroka Miyagawa, Yuto Kawauchi +6 more
We report the perinatal course and practical, axis-specific management of a 34-year-old woman with panhypopituitarism and arginine vasopressin deficiency (AVP-D) consequent to cranial irradiation and ifosfamide, cisplatin, and etoposide chemotherapy for a germinoma who conceived via in vitro fertilization.
Adrenal Insufficiency Due to Inhaled Etomidate in Electronic Cigarettes.
AACE Endocrinol Diabetes
Eng-Loon Tng, Aye Thida Aung, Yee Sian Tiong
A 33-year-old female presented with recurrent fainting. There was no hyperpigmentation, hirsutism, virilization, or oligomenorrhoea. She had not used antifungal medications, mitotane, metyrapone, or exogenous steroids. Her blood pressure was 135/83 mmHg when supine and 84/62 mmHg on standing. She was afebrile (36.8 °C) and her pulse rate was 81/min. Investigations showed: serum potassium 3.9 mmol/L (3.3 - 5.1), bicarbonate 25 mmol/L (21 - 32 mmol/L), peak cortisol on 250 mcg adrenocorticotropic hormone stimulation test 36 nmol/L, adrenocorticotropic hormone 29.7 pmol/L (1.6 - 13.9), 17-alpha-hydroxyprogesterone 3.6 nmol/L (0.3 - 3.3), dehydroepiandrosterone sulphate 2.6 umol/L (2.6 - 13.9), plasma aldosterone concentration 152 pmol/L (83 - 731), plasma renin activity 0.97 ng/ml/h (0.40 - 6.38), undetectable 21-hydroxylase antibody, and absence of adrenal hyperplasia or atrophy on computed tomography. Primary adrenal insufficiency was diagnosed. She was treated with hydrocortisone and dehydroepiandrosterone. Two months later, she admitted to using electronic cigarettes containing etomidate.
Newer Generation Immunoassays in Screening for Adrenal Insufficiency: Comparison of Baseline Morning Cortisol Levels With Cosyntropin Stimulation Testing.
AACE Endocrinol Diabetes
Ekta Shrestha, Stewart G Albert, Allina Ghimire +3 more
Serum cortisol immunoassays with improved specificity for cortisol have prompted revisiting the definition of a normal response at 60-minute cosyntropin stimulation testing (CST-60) to ≥14 μg/dL. European and American Endocrine Societies define values of AM cortisol >10 μg/dL as adequate to rule out adrenal insufficiency (AI) in patients with long-term use of corticosteroids. We sought to compare AM cortisol levels with CST-60 in patients suspected of AI from various causes.
Precipitated Adrenal Insufficiency by Osilodrostat and Fluconazole in Ectopic Adrenocorticotrophic Hormone Syndrome With a Pituitary Microadenoma and Cryptococcus Infection.
AACE Endocrinol Diabetes
Kristen Lee, Carolina Mendes Pessoa, Wenyu Huang
Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a challenging condition, particularly when the primary tumor cannot be localized. This case report described a patient with EAS and a concomitant pituitary tumor who developed adrenal crisis while receiving osilodrostat for EAS and fluconazole for cryptococcal infection before bilateral adrenalectomy.
Ectopic Cushing Syndrome due to an Adrenocorticotropic Hormone-Producing Pheochromocytoma.
AACE Endocrinol Diabetes
George A Stamatiades, Athanasios Bikas, Hina J Shah +4 more
Pheochromocytomas are rare catecholamine-secreting tumors arising from adrenomedullary chromaffin cells. Very rarely, they cosecrete adrenocorticotropic hormone (ACTH), causing ectopic Cushing syndrome. Because of its rarity, clinicians may not consider this etiology, despite the high morbidity associated with simultaneous catecholamine and cortisol excess. We present a case in which a systematic and methodical diagnostic approach led to identification and successful treatment of an ACTH-producing pheochromocytoma.
Cartilage calcification of the ears secondary to adrenal insufficiency.
Skin Health Dis
Luis Escalante, Carmen Santamaria, Astrid Maldonado +2 more
Calcification of the auricular cartilage is a rare condition, associated with either local or systemic causes. Among systemic causes, endocrine disorders, particularly adrenal insufficiency, are the most frequently reported. A 41-year-old man presented with a 1-year history of stiffness and pain in both ears. The ears became swollen and erythematous and, over time, they became painful to touch or move. Physical examination revealed rigid, immobile auricles. Biopsy, X-ray and computed tomography (CT) confirmed cartilage calcification. Laboratory tests showed markedly low cortisol and adrenocorticotropic hormone levels, leading to the diagnosis of secondary adrenal insufficiency. Auricular cartilage calcification is a rare but significant manifestation of adrenal insufficiency. Skull X-rays, noncontrast CT and laboratory tests are essential for diagnosis. No effective treatment currently exists to reverse calcification. Early recognition and hormone replacement therapy can prevent further progression.
Prognostic significance of atrial functional mitral regurgitation in patients with HFpEF and end-stage renal disease.
Front Cardiovasc Med
Yuanyuan Wang, Bingya Lv, Yangyang Chen +8 more
Atrial functional mitral regurgitation (AFMR) is common in patients with heart failure with preserved ejection fraction (HFpEF) and end-stage renal disease (ESRD) undergoing hemodialysis, but its prognostic value and potential diagnostic biomarkers remain unclear.
Paradigm shift: from pulmonary vasodilation to cardiopulmonary dual-track therapy-a comprehensive review of pathophysiology and advances in pulmonary hypertension-associated right heart failure.
Respir Res
Rongtao Chen, Chang Liu, Jiange Han +2 more
Pulmonary arterial hypertension (PAH)-induced right heart failure (RHF) remains a major determinant of poor patient outcomes, driven by multifaceted pathophysiological mechanisms including impaired right ventricle-pulmonary artery coupling, metabolic reprogramming, mitochondrial dysfunction, chronic inflammation, and gut–lung axis disruption. Traditional therapies focusing solely on pulmonary vasodilation provide symptomatic relief but often fail to halt progressive right heart deterioration. Recent advances underscore a paradigm shift toward cardiopulmonary dual-track strategies that simultaneously reduce right ventricular afterload and directly protect or enhance right heart function. Novel agents such as Sotatercept—an activin signaling inhibitor—significantly reverse vascular remodeling and improve hemodynamics. Metabolic modulators (e.g., metformin), mitochondrial-targeted antioxidants (e.g., Elamipretide), and immunomodulators (e.g., tocilizumab) show promise in correcting bioenergetic deficits and inflammatory activation. Interventional approaches like percutaneous pulmonary artery denervation (PADN) and atrial septostomy serve as effective bridging options, while percutaneous right ventricular assist devices (pRVADs) and extracorporeal membrane oxygenation (ECMO) offer critical circulatory support in end-stage disease. Emerging therapies—including gene editing, cell-based treatments, and exosome technology—hold potential for targeted, personalized intervention. Despite these innovations, challenges persist such as variable treatment responses, long-term safety concerns, and translational inefficiencies. Future efforts should prioritize multi-omics-guided precision medicine, multidisciplinary care integration, and novel technologies like CRISPR/Cas9 to advance disease-modifying therapies and improve quality of life.
Evaluation of the Safety, Efficacy and Pharmacokinetics of BGM0504 in Chinese Adults With Type 2 Diabetes: A Multicentre, Randomised, Controlled and Double-Blind Phase II Trial.
Diabetes Obes Metab
Ping Jin, Linong Ji, Yangqing Huang +7 more
This study aimed to evaluate its safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy in Chinese adults with T2DM and to preliminarily compare its efficacy and safety with semaglutide through multiple subcutaneous injections.