Sharp Laboratory

Assistant Professor @USFHealth, Cardiovascular Scientist,
#Cardiometabolic Disease, #HeartFailure @ECI_ISHR

[Michael Morelli @morellifit]

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.

[Sharp Laboratory @Sharp_Lab]

@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.

[Eric Topol @EricTopol]

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 https://t.co/82tRkOvQ49

[Sharp Laboratory @Sharp_Lab]

@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.

[Daniel J Drucker @DanielJDrucker]

Impressive TRIUMPH-1 #weightloss data for retatrutide https://t.co/aGDw3JcZmf

[Sharp Laboratory @Sharp_Lab]

https://t.co/Q0KMKRakdx

[Daniel J Drucker @DanielJDrucker]

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. https://t.co/cq1C4073FB

[Eric Topol @EricTopol]

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
https://t.co/or9VaPjD8J

[Circulation @CircAHA]

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 https://t.co/Sb463AueV4

[Circulation @CircAHA]

Multi-organ physiologic deficits during exercise and their metabolic signatures predict incident HFpEF and HF outcomes https://t.co/0j0Q4aTELg

[ThePeptideList @PeptideList]

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.

[Dr Alo, DO, FACC @MohammedAlo]

Proposed Multidisciplinary Transition Protocol For Patients Undergoing Treatment Using GLP-1RA

https://t.co/SE5weSDKCV

@DrNadolsky @NutritionMadeS3 @drmatthewnagra @BevTchangMD @MichaelAlbertMD

[Eric Topol @EricTopol]

A new review of the GLP-1 receptor drugs @NEJM
https://t.co/PK03jApZWB
surprisingly, the word inflammation only appears once, in this diagram

[Daniel J Drucker @DanielJDrucker]

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 https://t.co/Yl7TSPRrmZ

[Circulation @CircAHA]

Obesity phenotypes and cardiovascular disease https://t.co/pvIt0Mgoh8

[Daniel J Drucker @DanielJDrucker]

Hyperinsulinemia, adiposity, causality and #obesity The latest perspectives https://t.co/5gLNu8Xy5L

[Pablo Corral MD @drpablocorral]

👉 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 https://t.co/hws1UIUOYm

@society_eas
@escardio

[Eric Topol @EricTopol]

New ACC/AHA Guidelines published today for lipids
address measuring Lp(a) and ApoB
https://t.co/jO8ZG7iltN

[Scott Isaacs @scottisaacsmd]

Reduced-frequency GLP-1 as a maintenance strategy: in this case series, patients who tapered from weekly semaglutide/tirzepatide to less frequent dosing maintained weight loss, body composition, and metabolic syndrome gains, supporting structured de-escalation to lower burden without sacrificing efficacy.
https://t.co/xfKxfOb858

[Daniel J Drucker @DanielJDrucker]

The BELIEVE study, the efficacy and safety of intravenous bimagrumab and open-label subcutaneous semaglutide, alone or in combination, in adults with #obesity https://t.co/gQLNW556cL