Megestrol Acetate

This case report highlights an overlooked cause of hyperglycemia and risk of polypharmacy in a patient with end-stage renal disease (ESRD).

A 75-year-old non-English speaking male with T2DM, hypertension, coronary artery disease status post percutaneous coronary intervention, and ESRD secondary to IgG Kappa nephropathy on nightly peritoneal dialysis reported a loss of appetite, decrease in weight, and an increase in symptoms of depression. As a result of these symptoms, his nephrologist initiated megestrol acetate (MA), an agent commonly used in ESRD to help stimulate appetite and improve weight. After starting MA, his blood glucose (BG) significantly worsened, due to its glucocorticoid properties. Basal insulin was started to manage his hyperglycemia, but there was minimal improvement in BG. As the patient was referred to the endocrinology clinical pharmacist for diabetes management, it was identified that his weight loss began after starting dulaglutide, which led to a weight loss of 11 kg (12.9%). The Naranjo algorithm was used, and he had a score of 6, which is a probable reaction. The patient's endocrinology and nephrology teams agreed to discontinue MA and dulaglutide as they resulted in opposing effects on appetite and BG, as well as insulin glargine. The patient's BG was tightly controlled off MA and his appetite, weight, and mood improved off dulaglutide.

This case report reflects the potential effects of polypharmacy in ESRD, resulting in poor patient outcomes and drug interactions. It is imperative that a comprehensive medication reconciliation is completed on all patients, especially for patients on dialysis. It is also important for healthcare professionals to be cognizant of medications that may exhibit glucocorticoid properties, which can cause hyperglycemia. Including a clinical pharmacist in the care team can assist with medication reconciliation, screening for drug interactions and polypharmacy, and optimizing chronic disease management.

Leptin is a reliable predictive and surrogate marker of the efficacy of multitargeted treatment of cancer cachexia.

To the best of our knowledge, no study has assessed the predictive role of biomarkers in establishing the effectiveness of anti-cachectic treatment, which remains a complex issue. Herein, we aimed to find a marker that can detect early response to anti-cachectic treatment.

From January 2012 to December 2022, all consecutive eligible advanced cancer patients with cachexia were prospectively enrolled in an exploratory and validation cohort according to eligibility criteria. All patients received a combined anti-cachectic treatment consisting of megestrol acetate plus celecoxib plus l-carnitine plus antioxidants that showed efficacy in a previous phase III randomized study. Primary endpoints were an increase in lean body mass (LBM), a decrease in resting energy expenditure (REE), a decrease in fatigue, and improvement in global quality of life.

A total of 553 consecutive patients were recruited. Twenty patients dropped out, equally distributed over the exploratory (11 patients) and validation (9 patients) cohorts, for early death due to disease progression. Then, 533 patients were deemed assessable. Leptin level changes inversely correlated with circulating levels of inflammatory mediators and reflected the improvement of body composition, energy metabolism, functional performance, and quality of life. At multivariate regression analysis, at week 8, leptin change was an independent predictor of LBM, skeletal muscle index (SMI), grip strength increase, and REE; at week 16, leptin change was an independent predictor of the same parameters and improvement in Eastern Cooperative Oncology Group performance status. The ability of leptin to predict changes in LBM, SMI, REE, and grip strength was superior to that of other inflammatory markers when comparing the receiver operating curves. Moreover, increasing delta leptin values were associated with significantly better outcomes in LBM, SMI, REE, grip strength, and fatigue.

Leptin is a reliable predictive marker for multitargeted anti-cachectic treatment outcomes. Thus, it can be an ideal candidate for monitoring and predicting the effects of anti-cachectic treatment and a surrogate marker of the immune-metabolic actions of the selected drugs.