SwampNut Posted July 4 Posted July 4 https://substance-over-noise.beehiiv.com/p/the-patient-barely-lost-weight-he-got-better-anyway A true miracle drug? Also this is specifically about Semaglutide, but probably applies equally to Tirzepatide and Retatrutide. Almost surely doesn't correlate with Cagrilintide or Eloralintide however. Clinical Takeaway Domain Key Finding Evidence Level Cardiovascular 20% MACE reduction (SELECT); benefit independent of weight loss FDA Approved Heart Failure (HFpEF) 38% reduction in CV death / worsening HF events (SUMMIT) Phase 3 RCT Chronic Kidney Disease (with T2D) 24% reduction in kidney composite; FLOW stopped early for benefit FDA Approved (T2D + CKD) Metabolic Liver Disease 63% vs 34% steatohepatitis resolution (ESSENCE) FDA Approved Obstructive Sleep Apnea ~20 fewer apnea events/hr vs placebo (SURMOUNT-OSA) FDA Approved Peripheral Artery Disease Significantly improved maximum walking distance (STRIDE) Phase 3 RCT Osteoarthritis −41.7 vs −27.5 WOMAC pain improvement (STEP 9) Phase 3 RCT Substance Use Disorders HR 0.64 for AUD hospitalization; real-world signal robust Observational + Small RCT Lean Mass / Muscle 20–40% of weight lost can be lean mass; exercise is the fix Emerging Concern 1 Quote
SwampNut Posted July 10 Author Posted July 10 I've used Semaglutide, Tirzepatide, Retatrutide, and Cagrilintide over three years and a few months. My primary need is blood sugar control, weight is just a small side effect. My current usage is to combine tirz, reta, cagri. Crazy? Sure. I'm not the only one, and in particular cagri is already sold as a combo with sema. Let's just forget sema since it's the least effective of all. Retatrutide had the most undesirable side effects for me, but lots of other people respond differently. The bottom line is that nothing I tell you will help you know which is best for you. OTOH, Cagrilintide has no noticeable side effects, but a lot of people report big ones. What I've done is combine them in small amounts on various days until I had the least bad side effects, but kept the blood sugar control (I often wear a CGM so I can make objective decisions and changes). A lot depends on your dosage too, because I need max dosage of any of them to control sugar. Some people stay on lower doses forever. I've been heavily involved in peptide circles for many years, and have even spoken at a conference. People ask me for help all the time and this is what I advise... Go with Tirzepatide if you just want something solidly proven to be great, and FDA approved, and pretty cheap (from my sources, not TikTok ads). Retatrutide adds a third agonist (I assume you know some things to start with, ask if not) which is likely to have additional benefits, in particular, liver and kidney repair for some people. But seems to add new side effects for some people. Cagrilintide...not sure what to say on that, it is not a GLP-1, somewhat new, going to be very different. Probably nothing to dabble in from the start. This is also impossible to test and react to quickly. Tirzepatide has a 117.5 hour half-life, takes 36 hours to even max out in your body per dose, and takes three doses to build to full strength. A month is your minimum test time, and then you decide whether to increase dose. Making a change similarly takes a long time to see results of the change. Quote
02XXCA Posted September 23 Posted September 23 (edited) Quote With recent reports of possible blindness caused by NAION risks in the 1 in 10,000 patients taking GLP-1 drugs This article In JAMA seems to point out a much higher risk as the cohort of Type 2 diabetes patients that were over weight was about 20 events for a total group size of less than 17K so the numbers or risk don't add up. https://www.reviewofoptometry.com/news/article/popular-type-2-diabetes-drug-associated-with-increased-risk-of-naion Edited September 23 by 02XXCA Quote
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