Metabolic health & weight
Metabolic syndrome, insulin resistance, and fatty liver share a root, and the same tools keep appearing across them. The GLP-1 and dual/triple agonists have the strongest data; the supplement side is a mix of modest signal and hype. Here is the honest read.
GLP-1 & incretin weight loss
The pivotal trials and head-to-heads behind the incretin era.
What the semaglutide weight-loss trials actually showed
STEP 1, STEP 4, and SELECT — the efficacy, the rebound, and the cardiovascular signal, read straight from the primary literature.
Tirzepatide vs semaglutide for weight loss: what the trials actually support
Most comparisons are cross-trial. Only SURPASS-2 and SURMOUNT-5 randomized one drug against the other — here's the precise distinction.
Retatrutide: the triple agonist and what its Phase 2 data actually show
A single peptide hitting GIP, GLP-1 and glucagon produced the largest weight-loss numbers yet reported — in Phase 2. A straight read of the evidence and its limits.
GLP-1 medications and muscle: what the body-composition data actually show
Some of the weight lost is lean mass — but the substudies show fat falls faster, the ratio improves, and resistance training plus protein is what protects muscle.
Insulin sensitivity & metabolic support
The metabolic supplements and older drugs — berberine, acarbose, and the newer entrants.
Berberine: real evidence for blood sugar, not for weight loss
A plant alkaloid that activates AMPK and lowers glucose and LDL in human trials — with effects on blood sugar comparable to oral diabetes drugs. But it's not a GLP-1, and 'nature's Ozempic' is a myth.
Berberine vs metformin: same switch, very different evidence
Both activate AMPK, and in a small head-to-head berberine's glucose-lowering matched metformin's. But metformin is an approved drug with decades of data; berberine is a low-certainty supplement.
Acarbose and longevity: a carb-blocker with a real mouse-lifespan signal
An approved diabetes drug that repeatably extended lifespan in NIA mice — more in males. A straight read of the mouse data, the human gap, and the side-effect ceiling.
Calcium AKG (Rejuvant): a real metabolite, an overstated headline
Alpha-ketoglutarate declines with age and compresses morbidity in mice — genuinely interesting. But the viral 'about 8 years younger' claim comes from an uncontrolled, industry-linked clock study, and no human trial shows a hard outcome.
5-Amino-1MQ: an elegant mechanism with no human trials
An NNMT inhibitor that reverses obesity in mice by sparing the NAD+ pool — without reducing food intake. The mechanism is plausible; the human evidence is nonexistent.
Fatty liver (MASH)
The incretins and compounds studied in metabolic-associated liver disease.
Semaglutide for MASH: what the ESSENCE trial and the FDA approval actually say
Semaglutide 2.4 mg hit both liver endpoints in Phase 3 and won an FDA approval for MASH in 2025 — but for a specific F2–F3 population, under the accelerated pathway. A precise read of the evidence.
Survodutide (BI 456906): the GLP-1 / glucagon dual agonist and its Phase 2 data
An investigational dual agonist that adds glucagon to GLP-1 — with about 15% weight loss and standout MASH results in Phase 2. A straight read of the evidence and its limits.
Pemvidutide: the GLP-1/glucagon dual agonist betting on lean-mass preservation
Altimmune's investigational dual agonist isn't chasing the biggest weight-loss number — it's chasing better body composition and liver benefit. A straight read of the Phase 2 evidence.
TUDCA: real bile-acid biology, an approved parent drug, and a failed flagship trial
TUDCA is a genuine ER-stress-calming chemical chaperone whose parent compound (UDCA/ursodiol) is an approved liver drug — but the longevity and broad supplement claims rest on mechanism and small or animal studies, and its highest-profile human program (ALS / Relyvrio) failed phase 3 and was withdrawn in 2024.