Sharp Laboratory @Sharp_Lab

The suppressed report that concluded there is no protective or safe level of alcohol consumption, now published. It was commissioned by US Congress Report jsad.com/doi/10.15288/j… Editorial jsad.com/doi/epdf/10.15… "Despite the study’s adherence to its mandate, its findings were sidelined.”

In today's @TheLancet there are 3 papers on cardiometabolic disease: biology, epidemiology, prevention/treatment. The sobering and all to common story from womb to tomb conveyed in this graphic thelancet.com/journals/lance… thelancet.com/journals/lance… thelancet.com/journals/lance…

I'm going through the retatrutide phase 3 data, and the cardiometabolic numbers are more interesting than the weight loss: - 24.1 cm off the waist on 12mg (9.5 inches) - significant drops in systolic blood pressure - triglycerides down - non-HDL cholesterol down - hsCRP down (a key marker of inflammation) I'm giving it a few years before people realize GLP-1s are more than just weight loss drugs.

Real Peptides @realpeptides

4 weeks ago

Retatrutide phase 3 obesity trial results are out, and it's safe to say that this is the next generation of obesity medicine: - 28.3% bodyweight lost on 12mg over 80 weeks (70.3 lbs) - 30.3% at 104 weeks in higher-BMI patients (85 lbs) - 45.3% of patients hit 30%+ weight loss -

53 130 2K 1.5M 778

@EricTopol Reta is the next breakthrough. Synergy btw GCGR agonist and anti-obesity effects of single/double-G is profound. Reta in Ms/Rt obese HFpEF models is promising! Differentially regulating PPAR in an organ specific manner. Reta > PPAR quintuple pan-agonism.

Retatrutide, a triple receptor drug for GLP-1, GIP, and glucagon, is the most powerful weight loss drug yet. A significant issue is too much weight loss among the trial participants. New randomized trial results announced today with 28% body weight loss. gift link nytimes.com/2026/05/21/sci…

@DanielJDrucker Reta is the next breakthrough. Synergy btw GCGR agonist amplifies the anti-obesity effects of single/double-G. Reta in Ms/Rt obese HFpEF models is wow! Differentially regulating PPAR in an organ specific manner. Reta>PPAR quintuple pan-agonism. Reta metabolic flexibility king.

Impressive TRIUMPH-1 #weightloss data for retatrutide investor.lilly.com/news-releases/…

nature.com/articles/s4157…

In SURPASS CVOT tirzepatide was associated with a reduced risk of major kidney events driven by a reduction in new-onset macroalbuminuria in PPL with low-to-moderate-risk CKD #T2D and slowed decline in kidney function in high-risk chronic kidney disease. thelancet.com/journals/landi…

In people with HFpEF (heart failure with preserved ejection fraction) and severe obesity, there is a heart muscle cell defect with sarcomere hyper-phosphorylation. Besides weight loss, sarcomere enhancers (not yet studied) may help. @ScienceMagazine science.org/doi/10.1126/sc…

The rapidly evolving landscape of incretin-based therapies, including GLP1 agonists, necessitates rethinking trial design. Authors present challenges of placebo-controlled trials & potential ways to limit placebo exposure ahajrnls.org/4t0TrPa

Multi-organ physiologic deficits during exercise and their metabolic signatures predict incident HFpEF and HF outcomes ahajrnls.org/41k5Hy2

Everyone's talking about retatrutide for weight loss (28.7%). Almost nobody's talking about what it does to your liver. More than 80% reduction in liver fat. Over 90% normalization rates. In a body composition substudy from the Phase 3 program. 100 million Americans have fatty liver disease. Most don't know it. There's no FDA-approved treatment for it besides "lose weight and hope." Retatrutide's glucagon receptor activation appears to directly target hepatic fat metabolism not just as a side effect of weight loss, but as a primary mechanism. This isn't a weight loss drug that happens to help your liver. It might be a liver drug that happens to cause weight loss. Phase 3 weight loss data drops first half of 2026. Watch this space.

Proposed Multidisciplinary Transition Protocol For Patients Undergoing Treatment Using GLP-1RA dom-pubs.onlinelibrary.wiley.com/doi/abs/10.111… @DrNadolsky @NutritionMadeS3 @drmatthewnagra @BevTchangMD @MichaelAlbertMD

A new review of the GLP-1 receptor drugs @NEJM nejm.org/doi/full/10.10… surprisingly, the word inflammation only appears once, in this diagram

Important new #weightloss option for people with overweight and #obesity Orforglipron, the first @US_FDA approved small molecule GLP-1 medicine. Innovation from Chugai and Eli Lilly investor.lilly.com/news-releases/…

Obesity phenotypes and cardiovascular disease ahajrnls.org/4ruMCVl

Hyperinsulinemia, adiposity, causality and #obesity The latest perspectives nature.com/articles/s4157…

👉 Metabolic Disorders and Cardiovascular Disease: Key Insights 👆 A recent ESC scientific statement highlights the central role of metabolic dysfunction in cardiovascular disease and the therapeutic implications of emerging cardiometabolic therapies. 👆 Key points: 📍 Cardiovascular disease is increasingly driven by metabolic dysfunction—obesity, type 2 diabetes, and dyslipidaemia act synergistically to accelerate atherosclerosis, heart failure, and arrhythmias. 📍 Metabolic disease disrupts myocardial energetics, promoting metabolic inflexibility, mitochondrial dysfunction, oxidative stress, and lipotoxicity. 📍 Modern cardiometabolic drugs provide benefits beyond glucose lowering. SGLT2 inhibitors and GLP-1–based therapies improve cardiovascular outcomes through pleiotropic mechanisms. 📍 Atherogenic risk extends beyond LDL-C, with triglyceride-rich lipoproteins and Lp(a) contributing to residual cardiovascular risk. 📍 Future progress will require a systems-biology approach, integrating multi-organ mechanisms, multi-omics data, and translational research. 👆 Bottom line: Cardiovascular disease should increasingly be understood as a systemic cardiometabolic disorder rather than an isolated vascular pathology. 🔗 Open Access academic.oup.com/eurheartj/adva… @society_eas @escardio

New ACC/AHA Guidelines published today for lipids address measuring Lp(a) and ApoB jacc.org/doi/10.1016/j.…