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Retatrutide

LY3437943, LY-3437943

Quick Stats
Studies 83
Trials 32
Score 3
2025 pubmed

[Glucagon-like peptide-1 receptor agonists: a new pharmacological treatment option for psychiatric illnesses?].

Himmerich. Hubertus H

Key Findings

  • GLP‑1 and related agonists improve insulin release, slow stomach emptying, and reduce appetite, aiding weight loss and metabolic health.
  • They show anti‑inflammatory, antioxidant, and neuroprotective actions in the brain, potentially benefiting mood, cognition, and neurodegenerative conditions.
  • Animal and early human data indicate they can modulate dopamine signaling in reward centers, hinting at possible effects on addiction and substance‑use behaviors.
  • Common side‑effects are gastrointestinal (nausea, vomiting, diarrhea); rare but serious risks include pancreatitis, kidney issues, and possible thyroid cancer.

Practical Outcomes

  • For biohackers interested in longevity and mental performance, GLP‑1 agonists like semaglutide may offer dual benefits for weight control and brain health, but they should be used under medical supervision. Retatrutide, a newer triple‑agonist, could provide stronger effects but is still experimental. Start with low doses to gauge GI tolerance, monitor blood work regularly, and be aware of the rare severe side‑effects.

Summary

GLP‑1 drugs (like semaglutide) and the newer triple‑agonist retatrutide not only help control blood sugar and curb appetite, they also appear to protect brain cells, lower inflammation, and may influence addiction‑related pathways. Early reports suggest they could help with depression, anxiety, dementia, and substance‑use issues, but the main side‑effects are stomach‑related and rare serious risks.

Abstract

Albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, orforglipron and semaglutide are glucagon-like peptide‑1 (GLP-1) receptor agonists. Tirzepatide targets not only GLP‑1 but also glucose-dependent insulinotropic peptide (GIP) receptors and retatrutide is a triple GLP‑1, GIP and glucagon receptor agonist. The GLP‑1 receptor agonists increase insulin release but suppress glucagon release. They slow down the emptying of the stomach and thus prevent blood sugar spikes. They reduce appetite and food intake. In the brain GLP‑1 receptor agonists lead to a better glycemic control and they appear to have anti-inflammatory and neuroprotective effects. It has been reported that GLP‑1 receptor agonists reduce oxidative stress and apoptosis, lower the risk of ischemia and promote neurogenesis. The GLP‑1 receptor agonists can also influence dopaminergic signal transduction in the nucleus accumbens. Therefore, they could modify the effect of cocaine, alcohol and nicotine. Preliminary investigations provide indications of the therapeutic benefits of GLP‑1 receptor agonists for people with dementia, eating disorders, psychopharmacologically induced weight gain, depression, anxiety and substance use disorders. Typical accompanying adverse reactions are gastrointestinal side effects, such as nausea, vomiting, diarrhea, eructation and gastroesophageal reflux. More severe side effects include pancreatitis, allergic reactions, renal function disorders and possibly an increased risk of thyroid cancer.

Study Information

Provider

pubmed

Year

2025

Date

2025-03-05T00:00:00.000Z

DOI

10.1007/s00115-025-01813-x

References

31