Marilyn Tan

All Publications

• PREVENT: A Randomized, Placebo-Controlled Crossover Trial of Avexitide for Treatment of Post-Bariatric Hypoglycemia. The Journal of clinical endocrinology and metabolism Craig, C. M., Lawler, H. M., Lee, C. J., Tan, M., Davis, D. B., Tong, J., Glodowski, M., Rogowitz, E., Karaman, R., McLaughlin, T. L., Porter, L. 2021

  Abstract

  CONTEXT: Post-bariatric hypoglycemia (PBH), characterized by enteroinsular axis overstimulation and hyperinsulinemic hypoglycemia, is a complication of bariatric surgery for which there is no approved therapy.OBJECTIVE: To evaluate efficacy and safety of avexitide [exendin(9-39)], a GLP-1 antagonist, for treatment of PBH.DESIGN: Phase II, randomized, placebo-controlled crossover study (PREVENT).SETTING: Multicenter.PARTICIPANTS: Eighteen female patients with PBH.INTERVENTION: Placebo for 14 days followed by avexitide 30mg BID and 60mg QD, each for 14 days in random order.MAIN OUTCOME MEASURES: Glucose nadir and insulin peak during mixed-meal tolerance testing (MMTT) and hypoglycemic events captured by self-monitoring of blood glucose (SMBG), electronic diary, and blinded continuous glucose monitor (CGM).RESULTS: Compared to placebo, avexitide 30mg BID and 60mg QD raised the glucose nadir by 21% (p=0.001) and 26% (p=0.0002) and lowered the insulin peak by 23% (p=0.029) and 21% (p=0.042), corresponding to 50% and 75% fewer participants requiring rescue during MMTT, respectively. Significant reductions in rates of Levels 1-3 hypoglycemia were observed, defined, respectively, as SMBG<70mg/dL, SMBG<54mg/dL, and a severe event characterized by altered mental and/or physical function requiring assistance. CGM demonstrated reductions in hypoglycemia without induction of clinically-relevant hyperglycemia. Avexitide was well-tolerated, with no increase in adverse events.CONCLUSIONS: Avexitide administered for 28 days was well-tolerated and resulted in robust and consistent improvements across multiple clinical and metabolic parameters, reinforcing the targeted therapeutic approach and demonstrating durability of effect. Avexitide may represent a first promising treatment for patients with severe PBH.

  View details for DOI 10.1210/clinem/dgab103

  View details for PubMedID 33616643

• Real-time point-of-care total protein measurement with a miniaturized optoelectronic biosensor and fast fluorescence-based assay. Biosensors & bioelectronics Mahzabeen, F., Vermesh, O., Levi, J., Tan, M., Alam, I. S., Chan, C. T., Gambhir, S. S., Harris, J. S. 2020: 112823

  Abstract

  Measurement of total protein in urine is key to monitoring kidney health in diabetes. However, most total protein assays are performed using large, expensive laboratory chemistry analyzers that are not amenable to point-of-care analysis or home monitoring and cannot provide real-time readouts. We developed a miniaturized optoelectronic biosensor using a vertical cavity surface-emitting laser (VCSEL), coupled with a fast protein assay based on protein-induced fluorescence enhancement (PIFE), that can dynamically measure protein concentrations in protein-spiked buffer, serum, and urine in seconds with excellent sensitivity (urine LOD = 0.023 g/L, LOQ = 0.075 g/L) and over a broad range of physiologically relevant concentrations. Comparison with gold standard clinical assays and standard fluorimetry tools showed that the sensor can accurately and reliably quantitate total protein in clinical urine samples from patients with diabetes. Our VCSEL biosensor is amenable to integration with miniaturized electronics, which could afford a portable, low-cost, easy-to-use device for sensitive, accurate, and real-time total protein measurements from small biofluid volumes.

  View details for DOI 10.1016/j.bios.2020.112823

  View details for PubMedID 33715946

• Safety, Efficacy and Pharmacokinetics of Repeat Subcutaneous Dosing of Avexitide (Exendin 9-39) for Treatment of Post-Bariatric Hypoglycemia. Diabetes, obesity & metabolism Tan, M., Lamendola, C., Luong, R., McLaughlin, T., Craig, C. 2020

  Abstract

  AIMS: To evaluate the safety, efficacy, and pharmacokinetics of repeat dosing of two formulations of subcutaneous (SC) avexitide (exendin 9-39) in patients with post-bariatric hypoglycemia (PBH).METHODS: In this Phase 2, multiple-ascending-dose study conducted at Stanford University, 19 women with PBH underwent a baseline oral glucose tolerance test (OGTT) with metabolic and symptomatic assessments. Fourteen participants were then sequentially assigned to receive 1 of 4 ascending dose levels of twice daily (BID) lyophilized (Lyo) avexitide by SC injection for 3 days. On the basis of safety, efficacy and tolerability, 5 additional participants then received a novel liquid formulation (Liq) of avexitide by SC injection at a fixed dose of 30 mg BID for 3 days. All 19 subjects underwent a repeat OGTT on Day 3 of dosing to quantify metabolic, symptomatic, and pharmacokinetic responses.RESULTS: Treatment with Lyo avexitide reduced the magnitude of symptomatic hyperinsulinemic hypoglycemia at all dose levels, with dose-dependent improvements in glucose nadir, insulin peak and symptom score; doses ≥20 mg BID did not require glycemic rescue (administered at glucose <50 mg/dL). Participants receiving Liq avexitide 30 mg BID did not require any glycemic rescue, and on average achieved a 47% increase in glucose nadir, 67% reduction in peak insulin, and 47% reduction in overall symptom score. Equivalent doses of Liq vs Lyo avexitide yielded higher and more sustained plasma concentrations. Both formulations were well tolerated.CONCLUSIONS: In patients with PBH, BID administration of SC avexitide effectively raised the glucose nadir and prevented severe hypoglycemia requiring rescue intervention. Avexitide may represent a viable therapy for PBH.

  View details for DOI 10.1111/dom.14048

  View details for PubMedID 32250530

• A longitudinal big data approach for precision health. Nature medicine Schüssler-Fiorenza Rose, S. M., Contrepois, K. n., Moneghetti, K. J., Zhou, W. n., Mishra, T. n., Mataraso, S. n., Dagan-Rosenfeld, O. n., Ganz, A. B., Dunn, J. n., Hornburg, D. n., Rego, S. n., Perelman, D. n., Ahadi, S. n., Sailani, M. R., Zhou, Y. n., Leopold, S. R., Chen, J. n., Ashland, M. n., Christle, J. W., Avina, M. n., Limcaoco, P. n., Ruiz, C. n., Tan, M. n., Butte, A. J., Weinstock, G. M., Slavich, G. M., Sodergren, E. n., McLaughlin, T. L., Haddad, F. n., Snyder, M. P. 2019; 25 (5): 792–804

  Abstract

  Precision health relies on the ability to assess disease risk at an individual level, detect early preclinical conditions and initiate preventive strategies. Recent technological advances in omics and wearable monitoring enable deep molecular and physiological profiling and may provide important tools for precision health. We explored the ability of deep longitudinal profiling to make health-related discoveries, identify clinically relevant molecular pathways and affect behavior in a prospective longitudinal cohort (n = 109) enriched for risk of type 2 diabetes mellitus. The cohort underwent integrative personalized omics profiling from samples collected quarterly for up to 8 years (median, 2.8 years) using clinical measures and emerging technologies including genome, immunome, transcriptome, proteome, metabolome, microbiome and wearable monitoring. We discovered more than 67 clinically actionable health discoveries and identified multiple molecular pathways associated with metabolic, cardiovascular and oncologic pathophysiology. We developed prediction models for insulin resistance by using omics measurements, illustrating their potential to replace burdensome tests. Finally, study participation led the majority of participants to implement diet and exercise changes. Altogether, we conclude that deep longitudinal profiling can lead to actionable health discoveries and provide relevant information for precision health.

  View details for PubMedID 31068711

• Canagliflozin review - safety and efficacy profile in patients with T2DM. Diabetes, metabolic syndrome and obesity : targets and therapy Jakher, H. n., Chang, T. I., Tan, M. n., Mahaffey, K. W. 2019; 12: 209–15

  Abstract

  Canagliflozin is a sodium glucose-cotransporter (SGLT) receptor inhibitor approved for the treatment of type 2 diabetes mellitus (T2DM). This article reviews the mechanism of action of SGLT-2 receptor inhibitors and the efficacy of canagliflozin as an antidiabetic agent, its cardiovascular and renal benefits, and safety profile. During the development of canagliflozin, Phase II trials showed an improvement in cardiac and renal biomarkers such as blood pressure, body weight, and albuminuria. The large CANVAS program showed that canagliflozin reduced the composite cardiovascular outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The CANVAS program also showed a possible benefit of canagliflozin on a renal composite of sustained 40% reduction in estimated glomerular filtration rate, the need for renal replacement therapy, or death from renal causes. The safety profile of canagliflozin has been well characterized, and known side effects such as mycotic genital infections were confirmed in CANVAS. However, an increased risk of amputations was observed in CANVAS that requires further study. Overall, canagliflozin is an effective antidiabetic medication with cardiovascular and likely renal benefits, and with a generally well-tolerated safety profile. Results from the CREDENCE trial will further evaluate the safety and potential renal benefits of canagliflozin in patients with established diabetic nephropathy.

  View details for PubMedID 30787627

• 28-Day Dosing with Avexitide Improves Hyperinsulinemic Hypoglycemia in Patients with Severe, Refractory Post-Bariatric Hypoglycemia: The PREVENT Study Endocrine Society Lee, C., Lawler, H., Tan, M., Davis, D., Tong, J., Glodowski, M., Rogowitz, E., Lamendola, C., Karaman, R., Dar, M., Porter, L., Craig, C. 2019

  View details for DOI 10.1210/js.2019-OR20-5

• Effect of Electronic Clinical Decision Support on 25(OH) Vitamin D Testing. Journal of general internal medicine Chin, K. K., Hom, J. n., Tan, M. n., Sharp, C. n., Wang, S. n., Chen, Y. R., Chen, D. n. 2019

  View details for PubMedID 31090033

• Acromegalic cardiomyopathy: Epidemiology, diagnosis, and management. Clinical cardiology Sharma, A. N., Tan, M. n., Amsterdam, E. A., Singh, G. D. 2018; 41 (3): 419–25

  Abstract

  Acromegalic cardiomyopathy is the leading cause of morbidity and all-cause mortality in patients with acromegaly. Though acromegaly is a rare condition, the associated derangements are vast and severe. Stemming from an increase in circulating growth hormone (GH) and insulin-like growth factor-1 levels (IGF-1), acromegalic cardiomyopathy results in pathological changes in myocyte growth and structure, cardiac contractility, and vascular function. These molecular changes manifest commonly as biventricular hypertrophy, diastolic and systolic dysfunction, and valvular regurgitation. Early recognition of the condition is paramount, though the insidious progression of the disease commonly results in a late diagnosis. Biochemical testing, based on IGF-1 measurements, is the gold standard of diagnosis. Management should be centered on normalizing serum levels of both IGF-1 and GH. Transsphenoidal resection remains the most cost-effective and permanent treatment for acromegaly, though medical therapy possesses benefit for those who are not surgical candidates. Ultimately, achieving control of hormone levels results in a severe reduction in mortality rate, underscoring the importance of early recognition and treatment.

  View details for PubMedID 29574794

• Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet (London, England) Hernandez, A. F., Green, J. B., Janmohamed, S. n., D'Agostino, R. B., Granger, C. B., Jones, N. P., Leiter, L. A., Rosenberg, A. E., Sigmon, K. N., Somerville, M. C., Thorpe, K. M., McMurray, J. J., Del Prato, S. n. 2018; 392 (10157): 1519–29

  Abstract

  Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke.We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30-50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515.Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68-0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group.In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes.GlaxoSmithKline.

  View details for DOI 10.1016/S0140-6736(18)32261-X

  View details for PubMedID 30291013

• Repeat Subcutaneous Dosing of Exendin 9-39 Reduces Hyperinsulinemic Hypoglycemia and Neuroglycopenic Symptoms in Patients with Post-Bariatric Hypoglycemia American Diabetes Association 77th Scientific Sessions Tan, M., Luong, R., Lamendola, C., Liu, L., Craig, C. 2017
• Power Failure: Acromegalic Cardiomyopathy. The American journal of medicine Mantri, N. M., Amsterdam, E. n., Tan, M. n., Singh, G. D. 2016

  View details for PubMedID 27039953

• Does Polycystic Ovarian Syndrome Increase Insulin Resistance Above and Beyond Obesity? Endocrinology and Metabolic Syndrome Tan, M., Kim, S. H. 2014; 3 (142)

  View details for DOI 10.4172/2161-1017.1000142

• Patient whiteboards to improve patient-centred care in the hospital. Postgraduate medical journal Tan, M., Hooper Evans, K., Braddock, C. H., Shieh, L. 2013; 89 (1056): 604-609

  Abstract

  Patient whiteboards facilitate communication between patients and hospital providers, but little is known about their impact on patient satisfaction and awareness. Our objectives were to: measure the impact in improving patients' understanding of and satisfaction with care; understand barriers for their use by physicians and how these could be overcome; and explore their impact on staff and patients' families.In 2012, we conducted a 3-week pilot of multidisciplinary whiteboard use with 104 inpatients on the general medicine service at Stanford University Medical Center. A brief, inperson survey was conducted with two groups: (1) 56 patients on two inpatient units with whiteboards and (2) 48 patients on two inpatient units without whiteboards. Questions included understanding of: physician name, goals of care, discharge date and satisfaction with care. We surveyed 25 internal medicine residents regarding challenges of whiteboard use, along with physical therapists, occupational therapists, case managers, consulting physicians and patients' family members (n=40).The use of whiteboards significantly increased the proportion of patients who knew: their physician (p≤=0.0001), goals for admission (p≤=0.0016), their estimated discharge date (p≤=0.049) and improved satisfaction with the hospital stay overall (p≤=0.0242). Physicians, ancillary staff and patient families all found the whiteboards to be helpful. In response, residents were also more likely to integrate whiteboard use into their daily work flow.Inpatient whiteboards help physicians and ancillary staff with communication, improve patients' awareness of their care team, admission plans and duration of admission, and significantly improve patient overall satisfaction.

  View details for DOI 10.1136/postgradmedj-2012-131296

  View details for PubMedID 23922397

• Metastatic Burkitt's lymphoma presenting as diabetes insipidus. Endocrine practice Tan, M. J., Aguinaldo, T. F. 2013; 19 (4): e102-4

  Abstract

  Objective: To present the first reported case of metastatic Burkitt's lymphoma with a single central nervous system (CNS) metastasis to the pituitary stalk.Methods: Case presentation, review of literature.Results: Though other malignancies are known to metastasize to the pituitary, and diabetes insipidus is often the presenting symptom, there has not been a previously reported case of Burkitt's lymphoma with a single CNS metastasis to the pituitary.Conclusion: A careful history and endocrine review of systems may aid early identification of pituitary or central nervous system metastases.

  View details for DOI 10.4158/EP12438.CR

  View details for PubMedID 23512390

• What is the Relationship between PCOS and Insulin Resistance? Tan, M. J., Kim, S. H. AMER DIABETES ASSOC. 2012: A418–A419

  View details for Web of Science ID 000209842903281

• Malignant Pheochromocytoma Presenting as Incapacitating Bony Pain PAIN PRACTICE Tan, M., Camargo, C. A., Mojtahed, A., Mihm, F. 2012; 12 (4): 286-289

  Abstract

  Among adrenal incidentalomas, pheochromocytomas are rare. Malignant pheochromocytoma is even less common, and it typically presents with classic hormonal symptoms, such as palpitations, labile blood pressures, and headaches. Bony metastasis usually occurs late in disease, but we report an unusual case of incapacitating bony pain as the initial presentation of malignant pheochromocytoma. Our patient is a 70-year-old woman with neurofibromatosis type 1 and a history of primary hyperparathyroidism, who tested negative for the ret mutation. She came to medical attention with chest pain and palpitations and was incidentally found to have an adrenal mass. Serum and urine testing was consistent with pheochromocytoma. Her blood pressure was easily controlled as she awaited elective adrenalectomy; however, she quickly developed severe, diffuse bony pain. She represented with hypercalcemia, spontaneous fractures, and incapacitating pain that required such high doses of pain medications that she had to be intubated. Further imaging and bone marrow biopsy confirmed metastatic neuroendocrine tumor. She received one round of chemotherapy with no change in her bony pain, which was her primary complaint. Unfortunately, her treatment options were limited by the heavy sedation required for comfort, and in the end, it was her bony pain rather than hormonal symptoms that made her disease untreatable.

  View details for DOI 10.1111/j.1533-2500.2011.00499.x

  View details for PubMedID 21884564