Pharmacoepidemiology, Volume 4, Issue 3 (September 2025) – 3 articles

Proton pump inhibitors (PPIs) are widely prescribed medications primarily used to treat gastroesophageal reflux disease, peptic ulcer disease, and upper gastrointestinal bleeding. Despite clear therapeutic benefits in appropriate contexts, widespread overprescribing and extended use without clear indications have prompted significant concerns about associated risks. Accumulating evidence, predominantly from observational studies, suggests that long-term PPI use may lead to complications such as vitamin and mineral deficiencies, increased risks of infections, dysbiosis, renal dysfunction, bone fractures, cardiovascular disease, and certain malignancies. This narrative review not only synthesizes the current evidence surrounding PPI-related harms and existing deprescribing guidelines but also offers a novel perspective on how stewardship principles can be applied to promote responsible PPI prescribing. In particular, we propose a stewardship-oriented deprescribing framework rooted in implementation science, focusing on provider behavior, patient engagement, and health system-level integration. Recognizing these potential harms, evidence-based deprescribing strategies such as tapering, intermittent dosing, and transitions to alternative therapies are critical to mitigate unnecessary patient exposure. Effective implementation of deprescribing requires addressing patient, provider, and institutional barriers through educational initiatives, policy support, and structured monitoring. By promoting judicious PPI prescribing and proactive stewardship practices, clinicians can significantly reduce medication-related harm and improve patient safety. Full article

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly encompassed under nonalcoholic fatty liver disease (NAFLD), is a growing global health burden associated with progression to cirrhosis and hepatocellular carcinoma. Resmetirom, a thyroid hormone receptor-β (THR-β) agonist, and semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), have emerged as promising agents targeting distinct metabolic and inflammatory pathways. This systematic review compares the safety and efficacy of resmetirom and semaglutide in MASLD. Methods: We conducted a comprehensive search of PubMed, Embase, and Google Scholar for randomized controlled trials and clinical studies published between January 2014 and April 2025, following PRISMA guidelines. Studies assessing the efficacy and safety of resmetirom and/or semaglutide in MASLD or NASH were included. Data extraction was performed by two independent reviewers, and a narrative synthesis was undertaken due to the heterogeneity in study design and outcome measures. Results: Fourteen studies encompassing over 4500 patients were analyzed. Resmetirom demonstrated consistent reductions in hepatic fat (≥30% in >50% of patients) and improvements in fibrosis (≥1 stage in up to 26.4% of patients), as evidenced in the MAESTRO-NASH trial. Semaglutide achieved higher rates of NASH resolution (up to 62.9%) without worsening fibrosis, especially among patients with type 2 diabetes or obesity, although fibrosis improvement was less consistently observed. Resmetirom was well tolerated with low discontinuation rates, while semaglutide was associated with more frequent, yet manageable, gastrointestinal adverse events. Conclusions: Both resmetirom and semaglutide show therapeutic potential for MASLD. Resmetirom offers more consistent antifibrotic effects, while semaglutide excels in NASH resolution and metabolic improvement. The absence of direct comparative trials underscores the need for future head-to-head studies to guide tailored treatment strategies in MASLD management. Full article