https://chat.peppys.org/u/nmcoyote1
There is a lot to unpack here. So I will have to think about different sections and reread it. But they mentioned “exposure to unstable compounded formulations” being a possible cause of things like immunogenisis. Hmmmm I wonder if that’s a thing and if it could be why we see different feels… excetra? Are peptides/ grey peptides really unstable?
How do GLP-1s affect the brain? Why does weight loss taper? Does long-term use lead to tolerance? All these questions remain unclear.
www.medscape.com
Here are 2 legit long term studies returned by Gemini:
Clinical studies on the long-term effects of tirzepatide (the active ingredient in
Mounjaro and
Zepbound) have expanded significantly as of 2026. While the drug is relatively new, researchers have now released data from trials spanning
three to four years, offering a better understanding of its sustained safety and effectiveness.
1. Three-Year Weight Management and Diabetes Prevention
The
SURMOUNT-1 trial is one of the longest completed studies to date, following participants for
176 weeks (roughly 3.4 years).
- Weight Loss Maintenance: Participants on the highest dose (15 mg) achieved and maintained an average weight reduction of 22.9% over the three-year period.
- Diabetes Risk Reduction: In adults with pre-diabetes and obesity, tirzepatide reduced the risk of progressing to type 2 diabetes by 94% compared to a placebo.
- Health Reversal: Nearly 99% of participants treated with the drug remained diabetes-free at the end of the 176-week treatment period.
2. Four-Year Cardiovascular and Mortality Outcomes
The
SURPASS-CVOT trial, published in late 2025, followed over 13,000 patients with type 2 diabetes and established cardiovascular disease for a
median of 4 years.
- Heart Protection: The study confirmed that tirzepatide is as effective as other leading treatments (like dulaglutide) in preventing major cardiovascular events, such as heart attacks and strokes.
- Survival Benefits: Results showed a significant reduction in all-cause mortality (8.6% vs 10.2%) over the four-year period.
- Kidney Health: Long-term use was also associated with slowing the decline of kidney function in high-risk patients.
3. Long-Term Safety and Side Effects
Data from these multi-year trials indicate that the safety profile remains consistent over time.
- Common Issues: Gastrointestinal symptoms (nausea, diarrhea, and constipation) are the most frequent side effects. These are typically most severe during the initial dose-escalation phase but can persist for some users.
- Serious Risks: Rare but serious events monitored in long-term studies include pancreatitis (occurring in <1% of participants) and gallbladder-related issues.
- Warnings: It remains contraindicated for individuals with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
4. Ongoing "Lifetime" Research
Because tirzepatide is often intended for chronic use, researchers are using 10-year and lifetime simulation models based on current trial data to predict future health gains. These models suggest that long-term use may continue to generate substantial health benefits by preventing long-term complications of obesity and diabetes.
