Breast surgery and combination cases default to KLOW because the inflammatory load is meaningful
Conclusions Collating the latest trial evidence from the past two years, this review supports the rationale for further investigation of the efficacy of NuSHs, particularly GLP-1RAs, in MASH, as well as their potential as a chemopreventive strategy against MASH-related HCC
**AOD-9604 clinical data:** - One Phase 2b clinical trial was conducted in approximately 300 obese adults in Australia - Results showed **no statistically significant difference** in weight loss between AOD-9604 and placebo groups - The trial was considered a failure, and Metabolic Pharmaceuticals did not advance AOD-9604 to Phase 3 - Total clinical weight loss data in humans: fewer than 500 participants across all studies - Typical AOD-9604 results reported anecdotally: 1-3 kg over several months **Semaglutide clinical data:** - The STEP clinical trial program included over **4,500 participants** across multiple Phase 3 trials - STEP 1 demonstrated **14.9% mean body weight loss** (vs 2.4% placebo) over 68 weeks - STEP 5 confirmed weight loss maintenance of approximately **15.2%** over two full years - STEP 4 showed that discontinuing semaglutide leads to weight regain, confirming its active role in fat loss - The SELECT trial (17,604 participants) demonstrated a **20% reduction in major cardiovascular events** - Total clinical participants: over 20,000 across all weight loss and cardiovascular trials | Metric | AOD-9604 | Semaglutide | |--------|----------|-------------| | Phase 3 weight loss trial | Failed / not completed | Multiple successful trials | | Mean weight loss (%) | Not statistically significant vs placebo | 14.9-16.9% body weight | | Total clinical participants | ~500 | 20,000+ | | FDA approval for weight loss | No | Yes (Wegovy) | | Cardiovascular outcomes data | None | Yes (SELECT trial 20% MACE reduction) | | Long-term data (2+ years) | None | Yes (STEP 5) | | Published in top journals | Limited | NEJM, JAMA, Lancet, Nature Medicine | ### Safety and Side Effects **AOD-9604 side effects:** - Generally well-tolerated in limited studies - Injection site reactions - Headache (infrequent) - No significant GI side effects - **Critical caveat:** The absence of side effects partly reflects the lack of robust biological activity in humans **Semaglutide side effects:** - Nausea (most common, typically transient resolves with dose titration) - Vomiting, diarrhea, constipation - Injection site reactions - Rare reports of pancreatitis - Well-characterized safety profile from extensive clinical trials - Most GI side effects can be managed with proper [dose titration](/guides/semaglutide-dosing-schedule-week-by-week-guide) For guidance on proper **peptide injection** technique to minimize discomfort, see our [GLP-1 injection guide](/guides/how-to-inject-glp1-medications-guide)
Li J, Somers VK, et al
Don't let poor quality undermine your hard work
Recently, their use has expanded to broader indications because of their proven benefits across various conditions, including cardiovascular disease, kidney disease, and obesity
