Knowledge
Sphere

GLP-1 receptor agonists (semaglutide, tirzepatide, liraglutide) mimic a gut hormone that regulates blood sugar and appetite. Originally developed for type 2 diabetes, they have since demonstrated broad effects across cardiovascular, neurological, and metabolic systems.

Metformin is the world's most prescribed diabetes drug — a biguanide compound approved in the UK in 1958 and the US in 1995. It lowers blood sugar primarily by suppressing hepatic glucose production via AMPK activation, without causing weight gain or hypoglycemia. Sixty years of clinical use have produced one of the densest evidence bases in medicine. Its most intriguing effects may still lie ahead: the TAME trial is testing whether metformin can slow human aging itself.

Lecanemab and donanemab are the first drugs proven to slow Alzheimer's disease progression — not just manage symptoms. Both are IV monoclonal antibodies that clear amyloid-beta plaques from the brain. Lecanemab (approved July 2023) targets toxic protofibrils; donanemab (approved July 2024) targets a modified form of amyloid unique to plaques. Both require confirmed amyloid pathology and APOE4 genetic testing before use. They represent a historic milestone: for the first time, treating the underlying disease rather than its downstream effects. The tradeoff is a significant safety burden — brain swelling and microbleeds occur in a meaningful fraction of patients, and the absolute cognitive benefit, while real, is modest at 18 months.

Statins are the world's most-prescribed drug class — taken by more than 35 million Americans daily. They block HMG-CoA reductase, the liver's rate-limiting enzyme for cholesterol synthesis, cutting LDL by 30–55%. Their cardiovascular evidence base is unmatched: 300,000+ patient-years across landmark trials, with a consistent 20–35% reduction in major cardiac events per unit of LDL lowering. The science is moving fast. A 2026 Oxford meta-analysis of 23 trials has definitively debunked most feared side effects as nocebo, new real-world data links statins to lower Alzheimer's risk, and emerging cancer research is opening a new chapter. The foundational classic of modern medicine may be far from finished.

Creatine is the most-studied, most-validated sports supplement in history — and one of the cheapest. Synthesized naturally in the liver from glycine and arginine, it is stored predominantly in skeletal muscle as phosphocreatine (PCr): the fuel reservoir behind every explosive movement, from a sprint to a back squat. The International Society of Sports Nutrition designates it "the most effective ergogenic nutritional supplement for increasing high-intensity exercise capacity and lean body mass during training." More than 500 RCTs back this up. The story doesn't stop at the gym. A decade of accumulating research on brain creatine has produced compelling 2025–2026 data on cognitive performance, depression augmentation, and even a first-in-human Alzheimer's pilot trial that confirmed creatine crosses the blood-brain barrier in meaningful amounts. Meanwhile, decades of feared side effects — kidney damage, cancer, dehydration, hair loss — are being systematically addressed by controlled trials and expert reviews, with most concerns either quantified as minor or debunked entirely. Standard dosing: 3–5 g/day continuously, with or without a loading phase.