Chagas disease, caused by Trypanosoma cruzi, is a leading cause of non-ischemic cardiomyopathy in Latin America, affecting 6–7 million people. Despite clear benefit of sacubitril/valsartan over enalapril in HFrEF of other etiologies (PARADIGM-HF trial), its efficacy in Chagas cardiomyopathy remained unknown due to distinct pathophysiology involving chronic inflammation, fibrosis, and microvascular dysfunction.
Endometrial cancer (EC), particularly the endometrioid subtype, remains a leading gynecologic malignancy with limited options for advanced, ER-positive disease. Preclinical models demonstrate synergistic antitumor effects from concurrent inhibition of estrogen receptor (ER), cyclin-dependent kinase 4/6 (CDK4/6), and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathways. Building on window-of-opportunity studies showing metformin’s suppression of PI3K/mTOR signaling in EC, we conducted a single-arm, non-randomized phase 2 trial (NCT03675893) to evaluate the combination of letrozole (an aromatase inhibitor), abemaciclib (a CDK4/6 inhibitor), and metformin (a PI3K/mTOR modulator) in patients with ER-positive endometrioid EC.
Hypertension remains a global health crisis, affecting over 1.4 billion people and serving as a leading risk factor for cardiovascular and renal diseases. Despite advances in antihypertensive therapies, approximately 50% of treated patients in the US fail to achieve blood pressure control with multiple agents, highlighting a critical unmet need in hard-to-control (uncontrolled or treatment-resistant) hypertension. Aldosterone, a hormone that promotes sodium and water retention, plays a pivotal role in this resistance, yet targeted interventions have been limited for over two decades.
Type 2 diabetes (T2D) in Asian Indians is characterized by high ectopic fat deposition in liver and pancreas, elevated Fetuin-A (an insulin resistance mediator), and hepatic fibrosis risk. While SGLT2 inhibitors like Dapagliflozin (DAPA) reduce hepatic and pancreatic fat, Metformin’s effects on these parameters, especially Fetuin-A and fibrosis, remain underexplored in this population.
Obesity, defined by WHO as BMI ≥30 kg/m² in adults, has escalated into a global epidemic, impacting over 1 billion individuals and contributing to 3.7 million deaths in 2024 alone. Projections indicate a doubling of prevalence by 2030, fueling noncommunicable diseases such as cardiovascular conditions, type 2 diabetes, and certain cancers, while exacerbating infectious disease outcomes. Economic burdens are forecasted to reach US$3 trillion annually by 2030. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs)—including liraglutide, semaglutide, and tirzepatide—have emerged as efficacious pharmacological options, promoting weight loss, glycemic control, and reductions in cardiovascular and renal risks, alongside lowered mortality in diabetes. In September 2025, WHO added select GLP-1 RAs to the Essential Medicines List for high-risk type 2 diabetes management. Responding to Member State requests, this inaugural WHO guideline on GLP-1 RAs for obesity treatment emphasizes their role within a comprehensive, person-centered framework incorporating diet, physical activity, and psychosocial support, aligning with the 2022 Acceleration Plan to Halt the Rise in Obesity.
