Semaglutide vs tirzepatide vs retatrutide: sorting fact from TikTok hype

What did @the_hempies actually say?

Honestly? It's hard to tell. The transcript provided for this video is largely incoherent, likely the result of poor auto-captioning of Afrikaans speech being run through an English speech-to-text engine. The creator's caption confirms the topic: comparing semaglutide, tirzepatide, and retatrutide, with an emphasis on how eating habits and lifestyle interact with each drug's mechanism. A few phrases do break through the noise. There's a reference to "food noise suppression" and "appetite suppressor," and a nod to "Type X" receptors, which loosely maps onto the dual and triple receptor agonist conversation. The creator also acknowledges upfront that there is "a lot I didn't mention," which is a reasonable disclaimer. We can't fact-check what we can't hear clearly, and we're not going to fill in the gaps with assumptions.

Does the science back up the core framing?

The general framing, that these three drugs differ meaningfully and that lifestyle context matters, is scientifically sound. That part holds up. Semaglutide is a GLP-1 receptor agonist. Tirzepatide adds GIP receptor activity. Retatrutide adds glucagon receptor activity on top of both. Each additional receptor target appears to shift the weight loss ceiling upward, but the mechanisms aren't identical and the side effect profiles aren't either.

The SURMOUNT-1 trial (Jastreboff et al., 2022, New England Journal of Medicine) showed tirzepatide at 15mg achieving up to 22.5% mean body weight reduction over 72 weeks. A phase 2 trial for retatrutide (Jastreboff et al., 2023, NEJM) showed up to 24.2% at 48 weeks, though this was a smaller study and phase 2 data should be interpreted cautiously. Semaglutide 2.4mg in STEP 1 (Wilding et al., 2021, NEJM) landed at roughly 14.9% mean weight reduction. The hierarchy the creator seems to gesture toward, with retatrutide being the "next level," is directionally consistent with current trial data.

On food noise specifically: this is a real, patient-reported phenomenon. A qualitative study by Chao et al. (2023, Obesity) documented reduced intrusive food thoughts in GLP-1 users, though "food noise" is not yet a standardized clinical endpoint.

What did they get wrong, or right?

We can't penalize the creator for things we couldn't hear. What we can say is that the framing around lifestyle and eating habits being a "main factor" is both right and potentially undersold. These drugs do not work identically across individuals. A 2023 analysis by Rubino et al. in Nature Medicine noted that protein intake, meal timing, and baseline metabolic health all modulate GLP-1 agonist response. The drugs suppress appetite, but they don't override dietary quality entirely.

If the creator implied, as some in this space do, that retatrutide is simply a stronger version of tirzepatide and tirzepatide is simply stronger than semaglutide, that's an oversimplification. Receptor pharmacology is not a straight line. Glucagon agonism in retatrutide increases energy expenditure but also carries hepatic and cardiovascular considerations that are still being studied in phase 3 trials. Calling it "better" without that context is misleading.

Credit where it's due: acknowledging what wasn't covered is genuinely good practice for a social media creator. Too few do it.

What should you actually know?

These three drugs represent different pharmacological strategies, not just different dose levels. Semaglutide targets one receptor, tirzepatide targets two, retatrutide targets three. More targets does not automatically mean safer or more appropriate for every person.

• Retatrutide is not approved anywhere as of mid-2025. Phase 3 trials are ongoing. It is not a treatment option through standard prescribing channels.
• Tirzepatide is FDA-approved for obesity (Zepbound) and type 2 diabetes (Mounjaro). Semaglutide is approved for both indications under different brand names.
• Compounded versions of these peptides are not equivalent to FDA-approved branded products. Potency, purity, and sterility standards differ. Do not assume otherwise.
• "Food noise suppression" is a real patient experience but is not a labelled indication for any of these drugs. It remains under active research.
• Side effect profiles diverge. Nausea and GI effects are common across all three, but retatrutide's glucagon component adds complexity that semaglutide users won't have encountered.

Lifestyle and eating habits genuinely matter here. These are not passive treatments. Protein intake in particular appears to influence lean mass preservation during GLP-1 induced weight loss (Wadden et al., 2023, Obesity). If your eating patterns don't shift, the long-term results likely won't either.