Dr Kuo

Extension Health
Founder and CEO
Longevity and Regenerative Medicine

[Dr Kuo @JonathannK]

Lean tissue on DXA is not the same as muscle. Strength testers were not blinded, and falls and fractures were not measured.

The take-home is still clear: if you're on a GLP-1, you need to lift weights.

Are you lifting while you're on one?
https://t.co/vqY7jQlxY7

[Dr Kuo @JonathannK]

If you're on a GLP-1, you need to lift weights.

A new randomized trial in Nature Medicine put that to a hard test. 120 adults aged 50 to 70 took tirzepatide for 40 weeks. Both groups lost about 50 pounds. Only one group lifted.

[Dr Kuo @JonathannK]

Blood pressure, glucose, and lipids improved similarly in both groups. Lifting did not add a metabolic edge here.

What it changed was the capacity to produce force. The authors argue that the emphasis should be on getting stronger, not just on slowing the loss of lean mass.

[Dr Kuo @JonathannK]

@biogerontology @davidasinclair @bot @bot let’s add this

[Dr Kuo @JonathannK]

@C_Angermayer This vision is clear to me as well and we are in it for the ride!

[Dr Kuo @JonathannK]

@dkmitc @bot can I use this calling feature

[Dr Kuo @JonathannK]

Source, the Federal Register notice (91 FR 68526):
https://t.co/BadQ5XADDS

[Dr Kuo @JonathannK]

HHS didn't "approve" peptides. It said it won't enforce against 503A compounding of six (incl. BPC-157, TB-500, MOTS-c) with a patient-specific Rx, tested lots and MedWatch reporting.

Interim, revocable, not FDA-reviewed for safety or benefit. Access widened; evidence didn't. What should be studied first?

[Dr Kuo @JonathannK]

@paolo_scales @bot take a look

[Dr Kuo @JonathannK]

@Josh_fitcheck13 One of many combination compounds to come !

[Dr Kuo @JonathannK]

Sources, both American Diabetes Association conference abstracts funded by the developer, Pep2Tango:
https://t.co/mt5tYMIIRc
https://t.co/OCGkVkxVb7

[Dr Kuo @JonathannK]

Meet PTT-A, an experimental peptide built to do what four of your metabolic hormones do, in a single molecule.

Today's leading weight-loss drugs hit one or two receptors. Semaglutide acts on GLP-1. Tirzepatide acts on GLP-1 and GIP. CagriSema pairs semaglutide with an amylin analog. PTT-A goes further and activates four receptors at once: GLP-1, GIP, amylin and calcitonin. Together these govern appetite, fullness, how fast the stomach empties, and how the body handles insulin and fat.

In diet-induced obese rats treated for 21 days, presented at the American Diabetes Association meetings:
• The higher dose cut body weight 19% compared with untreated rats. Tirzepatide and CagriSema each cut about 12%.
• Fat depots shrank 36 to 50% on PTT-A, compared with about 25% on the comparators.
• Leg muscle weight held steady on PTT-A. On tirzepatide it fell about 26%.
• Glucose, insulin and triglycerides improved more on PTT-A.

Now the honest limits. These are rats, not people. The studies lasted three weeks. The results are conference abstracts, not peer-reviewed papers, and the developer, Pep2Tango, funded the work. "Muscle preserved" here means muscle weight, not strength or function, and no human trial has started.

What interests me is the direction. Metabolic medicine is shifting from asking how much weight someone lost to asking what they lost. Losing muscle on a GLP-1 is a real clinical problem, and it's why we measure body composition on a DEXA scan instead of trusting the scale.

If the next generation of drugs truly spares muscle, is the scale the wrong scoreboard?

[Dr Kuo @JonathannK]

Retatrutide, still investigational, cut sleep apnea events by about 30 an hour in people with obesity in a new NEJM trial, vs about 10 on placebo. Baseline averaged 58.6 an hour, which is severe.

Extra weight narrows the airway. Many people with apnea don't know it. Test first.

[Eric Topol @EricTopol]

Retatrutide, the most potent GLP-1 agent in this family of drugs to date, had a marked benefit vs sleep apnea in a randomized trial, in people with obesity, just published @NEJM AHI-apnea-hypopnea index
https://t.co/W4rnr4Vy0A

[Dr Kuo @JonathannK]

@bot @bot set this up for me

[Jeff Tang @jefftangx]

People who cured / are curing their own cancer on X:

1/ @sytses - bone cancer, billionaire founder of Gitlab, developed 10+ personalized therapies for himself.

2/ @paul_conyngham - shrank his dog Rosie's mast cell cancer tumors after chemo and surgery weren't enough. Now backed by YC and Founders Fund

3/ @miriamgonp - stage 4 breast cancer, tumor sequenced, searching for vaccine manufacturer now

4/ @kevinace - stage 4 lung cancer, angel investor in 300+ companies, first drug stopped working after 18 months. Vaccine designed, now paying $300k out of pocket for the vaccine

5/ @masonbgrant: going founder mode on his his 32-year-old wife's rare liver cancer, sequencing her tumor with AI agents

6/ @ArunRLverma: former product leader at Atoms and Shopify, brain tumor, built a vaccine from his tumor. Now building an AI health agent startup based on what he went through

We're going to make it

[Bryan Johnson @bryan_johnson]

Your peptides may be coming fentanyl suppliers.

Anhui Renchen Technology was indicted in 2023 for supplying the Sinaloa Cartel with fentanyl precursors.

Their website currently sells semaglutide and melanotan II.

Of roughly 200 Chinese firms TRM Labs tracked selling fentanyl precursors, at least 50 now sell peptides.

The shipments enter the US in “master cartons” mislabelled as snack food, broken up by a domestic handler and mailed on. CBP has intercepted around 400 of those operations and seized over 130,000 vials in the past year.

FDA records surfaced showing two deaths, one in July and one in September, reported after people injected untested black market retatrutide.

[Dr Kuo @JonathannK]

The small print matters too. Chronic stress raises cortisol, which works against bone. Excess sodium, soda, and heavy alcohol make it harder to hold on to calcium.

Then remeasure. If the numbers aren't moving, that's when we talk hormones and medication.

[Dr Kuo @JonathannK]

World Osteoporosis Day. My advice: after 40, get a DEXA scan every year, especially if you're a woman. Then check CTX and P1NP, bone turnover labs that show whether you're losing bone faster than you're building it. Diagnose, then intervene. We do both at Extension Health.

[Dr Kuo @JonathannK]

Measuring is step one. Then you build. Bone peaks around 25-30 and declines after, and women can lose bone fast through menopause as estrogen drops.

The foundations: resistance training, impact and power work, enough protein, vitamin D and K2 with key minerals, and real sleep.