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[69.67.186.23]) by mx.google.com with ESMTPS id af79cd13be357-8d027ee02aesi1257027985a.101.2026.03.31.15.21.50 for (version=TLS1_3 cipher=TLS_AES_256_GCM_SHA384 bits=256/256); Tue, 31 Mar 2026 15:21:50 -0700 (PDT) Received-SPF: pass (google.com: domain of bounces+tjphuhs=gmail.com@bh.mail.beehiiv.com designates 69.67.186.23 as permitted sender) client-ip=69.67.186.23; Authentication-Results: mx.google.com; dkim=pass header.i=@bhmta.beehiiv.com header.s=bh header.b=UpjHUOvI; dkim=pass header.i=@mail.beehiiv.com header.s=bh header.b=eiqgX6bU; spf=pass (google.com: domain of bounces+tjphuhs=gmail.com@bh.mail.beehiiv.com designates 69.67.186.23 as permitted sender) smtp.mailfrom="bounces+tjphuhs=gmail.com@bh.mail.beehiiv.com"; dmarc=pass (p=REJECT sp=REJECT dis=NONE) header.from=beehiiv.com X-BmtaRef: eyJfQF8iOiJcXF8vIiwicmVjaXBpZW50IjoidGpwaHVoc0BnbWFpbC5jb20iLCJ4X2xpc3RfaWQiOiJmZDQxNjMwZS1lOTFmLTQ2ZDktYTI3NC1iNzQwZGFiNzU2ZDIiLCJ4X3N1YnNjcmliZXJfaWQiOiI5YzQwZDYzOS02ZTFkLTQyOTItYTlkNy0wZTRjYmJiNWQ1ZGIifQ== DKIM-Signature: v=1; a=rsa-sha256; d=bhmta.beehiiv.com; s=bh; c=relaxed/relaxed; bh=w0T/ZpVn2rjSNOvqrCLsipGucnZB4coW7u2TEUWYNnA=; h=from:subject:mime-version:content-type:content-transfer-encoding: list-unsubcribe:feedback-id:list-unsubscribe-post:reply-to:to:cc: content-type:feedback-id:from:subject:to; t=1774994753; b=UpjHUOvIFpVFwXAqeC4Lnj893P7c+9FT8XB97N0Zzan5Mn+o7ph+mGDeMA3kVhdIXUkSB9c76 ctKjRXIINo+sODTYAmgEpPrY5SxCKLRyl4IVM8dTyCWT0GKa7V1Ttq27B3HAID9VWX+HSeYO0Y6 hIpbjJGXp3mbxZ+7q9iZ9PWALlJG/4wNC0A9txfUj9/vr8Cx7sJQN3HYMSLTzrB51HH7N7SX7xA lhbT2C7IZLQAZPumIXKsfksCC7lRDgAcYZAnlSDaIZRCdd5omXISsGTUdR9uwfHmsVoV9lFdMWM GYwwODhquvG8qR1psG6iQD84q0OIIpq1VXPGdR+YQzLQ==; DKIM-Signature: v=1; a=rsa-sha256; d=mail.beehiiv.com; s=bh; c=relaxed/relaxed; bh=w0T/ZpVn2rjSNOvqrCLsipGucnZB4coW7u2TEUWYNnA=; h=from:subject:mime-version:content-type:content-transfer-encoding: list-unsubcribe:feedback-id:list-unsubscribe-post:reply-to:to:cc: content-type:feedback-id:from:subject:to; t=1774994753; b=eiqgX6bUR78Sa5BFgKJjFf2Lj9Sbti1ygfxcM/TsNaJIAZH1S2i3wgTs5XS+WNEtFk0yAafH9 YyDCbLHoW1bfzGxQX1P96bGuzPtc2Phhkav8tBBRNVnh6CaiXritPbPclmstsdIom/BlF1J+9sb CkeAehiaUL02Q8i9OmeHJAccJ0gJFZ59IJVxoFhr1jHMMorAr53ro6F7eW4WYKKlwd/v8b8lS7t Ofvk2suhyTsv91DG4hygY4fpwL2RMk8kYDOX/2ToV7sVOcTnmbC6Rxb9t6J21kcuiBGedBEgeHq zhhdbtV96Z3CAh/u1cvc2ujgDQrj/KE2XLJVUgfe3bww==; Received: from mail.beehiiv.com by bhmta(mta13) with HTTP id for ; Tue, 31 Mar 2026 22:05:53 +0000 Content-Type: multipart/alternative; boundary="4ERMwaIzTiCgGBekZQbqtg" To: "tjphuhs@gmail.com" Feedback-ID: bac748e8-5955-4d60-843a-d1807afd9efe:newsletter:fd41630e-e91f-46d9-a274-b740dab756d2:c8f61fda6a60803 From: Hunter Williams List-Unsubscribe: , List-Unsubscribe-Post: List-Unsubscribe=One-Click Reply-To: =?utf-8?Q?Hunter=27s_Health_Hacks?= Subject: The Next Wave of GLP-1s Is Coming X-Batch-Id: acaa2d68-d619-4f56-af26-85ce7636a9b9 X-Subscriber-ID: 9c40d639-6e1d-4292-a9d7-0e4cbbb5d5db sId: fd41630e-e91f-46d9-a274-b740dab756d2 x-beehiiv-ids: {"account_name":"https://huntershealthhacks.beehiiv.com/","campaign_id":"bac748e8-5955-4d60-843a-d1807afd9efe","category":"newsletter","email_generated_at":1774994751,"user_id":"fd41630e-e91f-46d9-a274-b740dab756d2"} x-beehiiv-type: newsletter x-list-id: fd41630e-e91f-46d9-a274-b740dab756d2 x-list-owner: x-newsletter: https://huntershealthhacks.beehiiv.com/p/the-next-wave-of-glp-1s-is-coming x-newsletter-id: https://huntershealthhacks.beehiiv.com/ x-newsletter-signup: https://huntershealthhacks.beehiiv.com/subscribe Mime-Version: 1.0 Date: Tue, 31 Mar 2026 22:05:53 +0000 Message-ID: <20260331.220553.986a58d9@mta13> --4ERMwaIzTiCgGBekZQbqtg Content-Type: text/plain; charset="utf-8" Content-Transfer-Encoding: quoted-printable Happy Tuesday! =0A=0AThere are two peptides quietly making waves in the cli= nical space that will demand all of our attention over the next 24 months. = =0A=0AThey don't work like semaglutide, they don't work like tirzepatide, a= nd the clinical data is turning heads.=0A=0AI just dropped a brand new vide= o breaking down survodutide and mazdutide.=0A=0ASurvodutide & Mazdutide | T= he GLP-1/Glucagon Duo That Could Rival Reta: (https://open.spotify.com/epis= ode/2IADOstRyI6FrZlNHriPJB?si=3DRrUyDtoqTuqGt3-NERu-Ww)=0A=0AToday=E2=80=99= s email will be a written email of the video and how these two peptides wll= l be changing the game. =0A=0ALet's get into it.=0A=0A=E2=80=94=E2=80=94=E2= =80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80= =94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94= =E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=0A= =0A**Background**=0A=0AMazdutide is a synthetic analog of oxyntomodulin. = =0A=0AIt was originally developed by Eli Lilly and licensed to Innovent Bio= logics for development and commercialization in China. =0A=0ALilly is handl= ing the US development separately. In June 2025, it became the world's firs= t approved GLP-1/glucagon receptor agonist when China greenlit it under the= brand name Xinermei for weight management. =0A=0AIt then received a second= approval in September 2025 for glycemic control in adults with type 2 diab= etes. US trials are currently in Phase 2, and FDA approval is estimated aro= und 2028 to 2029.=0A=0ASurvodutide is a 29-amino acid peptide co-invented b= y Boehringer Ingelheim and Zealand Pharma. It has not been approved anywher= e yet. But it holds FDA Breakthrough Therapy designations specifically for = MASH. =0A=0AThe Phase 3 SYNCHRONIZE trials are fully enrolled with over 1,4= 00 patients, and results are expected in the first half of 2026.=0A=0A=E2= =80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80= =94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94= =E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2= =80=94=E2=80=94=0A=0A**How They Work**=0A=0AYou already know how GLP-1 agon= ism works. It suppresses appetite, delays gastric emptying, stimulates insu= lin secretion, and inhibits glucagon release from alpha cells. =0A=0AHundre= ds of millions of people have used GLP-1 peptides at this point.=0A=0ASurvo= dutide and mazdutide are different because they have a glucagon receptor ag= onist on one side of the molecule. =0A=0AGlucagon agonism increases energy = expenditure. Studies show that acute glucagon infusion increases caloric ex= penditure by about 200 calories per day. =0A=0AThis happens through hepatic= fuel cycling, FGF-21 thermogenesis, and brown fat adipocyte activation. Ba= sically, your body burns more calories at rest.=0A=0AThen there's the liver= fat component. Glucagon activation increases hepatic beta-oxidation. It su= ppresses de novo lipogenesis. And it restores mitochondrial function. =0A= =0AThese are effects that GLP-1 agonism alone cannot replicate. =0A=0AWhen = glucagon agonism is combined with GLP-1 agonism in a single molecule, the G= LP-1 component counterbalances the glucose-raising effect of glucagon. =0A= =0ANo increased risk of hyperglycemia has been observed in trials of either= compound.=0A=0A=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2= =80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80= =94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94= =E2=80=94=E2=80=94=E2=80=94=E2=80=94=0A=0A**The Benefits **=0A=0AThe weight= loss numbers are impressive, but honestly, the metabolic benefits beyond f= at loss are what make these compounds exciting.=0A=0AMazdutide at 6 mg per = week showed an 80% reduction in liver fat in patients with baseline hepatic= steatosis. =0A=0ASurvodutide showed 62% MASH resolution versus just 14% on= placebo, with 67% of patients achieving greater than 30% liver fat reducti= on. =0A=0ABoth peptides also reduce waist circumference and systolic blood = pressure.=0A=0AImprovements in triglycerides, LDL cholesterol, and uric aci= d have been documented across multiple trials. =0A=0ASurvodutide showed dra= matic reductions in liver enzymes (ALT and AST), reflecting reduced liver i= nflammation.=0A=0AMazdutide produced A1C reductions of approximately 1.5-2.= 15%. =0A=0AThe heart rate increase with mazdutide was only about 2.6 beats = per minute at week 48. =0A=0ACompare that to what I typically see with reta= trutide, which is usually 5 to 10 beats per minute within a few weeks.=0A= =0A=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94= =E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2= =80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80= =94=E2=80=94=E2=80=94=0A=0A**Clinical Results Compared to Tirzepatide and R= etatrutide**=0A=0AHere's where we stack these up against the compounds you = already know. I put together a quick comparison chart so you can see it all= at a glance.=0A=0ACompound=0A=0A=0ADose=0A=0A=0AReceptors=0A=0A=0ATrial Du= ration=0A=0A=0AMax Weight Loss=0A=0A=0ALiver Fat Reduction=0A=0A=0A=0ASemag= lutide=0A=0A=0A2.4 mg/wk=0A=0A=0AGLP-1=0A=0A=0A68 weeks=0A=0A=0A~16%=0A=0A= =0AModerate=0A=0A=0A=0AMazdutide=0A=0A=0A6 mg/wk=0A=0A=0AGLP-1 + Glucagon= =0A=0A=0A48 weeks=0A=0A=0A~14%=0A=0A=0A~80%=0A=0A=0A=0ASurvodutide=0A=0A=0A= 4.8 mg/wk=0A=0A=0AGLP-1 + Glucagon=0A=0A=0A46 weeks=0A=0A=0A~18.7%=0A=0A=0A= ~67% (>30% reduction)=0A=0A=0A=0AMazdutide=0A=0A=0A9 mg/wk=0A=0A=0AGLP-1 + = Glucagon=0A=0A=0A60 weeks=0A=0A=0A~20% (non-diabetics)=0A=0A=0ANot yet repo= rted=0A=0A=0A=0AMazdutide=0A=0A=0A16 mg/wk=0A=0A=0AGLP-1 + Glucagon=0A=0A= =0A20 weeks=0A=0A=0A~21%=0A=0A=0ANot yet reported=0A=0A=0A=0ATirzepatide=0A= =0A=0A15 mg/wk=0A=0A=0AGLP-1 + GIP=0A=0A=0A72 weeks=0A=0A=0A~22%=0A=0A=0AMo= derate=0A=0A=0A=0ARetatrutide=0A=0A=0A12 mg/wk=0A=0A=0AGLP-1 + GIP + Glucag= on=0A=0A=0A48 weeks=0A=0A=0A~24%=0A=0A=0A~82-86%=0A=0A=0A=0A=0AWhen you com= pare mazdutide and tirzepatide at similar dosing, you're getting pretty com= parable fat loss numbers. =0A=0ATirzepatide hits GLP-1 and GIP. Mazdutide h= its GLP-1 and glucagon. Similar weight loss, but mazdutide provides liver f= at and energy expenditure benefits that GIP agonism simply does not.=0A=0AR= etatrutide is still king on paper. It hits all three receptors and delivers= the most weight loss. =0A=0ABut survodutide and mazdutide are not far behi= nd. And for people who need an alternative, or who want to cycle compounds = to maintain receptor sensitivity, these fill a real gap.=0A=0A=E2=80=94=E2= =80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80= =94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94= =E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2= =80=94=0A=0A**They're Not the Same**=0A=0AYou see these two listed together= as GLP-1/glucagon agonists and assume they're interchangeable. They're not= .=0A=0ASurvodutide is GLP-1 dominant. =0A=0AThe approximate ratio is about = 8:1, GLP-1 to glucagon. Think of it as semaglutide with a little glucagon c= herry on top. You get strong appetite suppression with a modest boost in en= ergy expenditure.=0A=0AMazdutide is almost 50/50. The ratio of GLP-1 to glu= cagon agonism is roughly balanced, though it slightly favors glucagon. =0A= =0AThat means more direct hepatic fat oxidation. More energy expenditure in= crease. And it explains why mazdutide is so good at reducing liver fat.=0A= =0AThis difference shows up in the tolerability data, too. =0A=0AMazdutide = had a remarkably clean tolerability profile. Only 0.5% of people at the 6 m= g dose discontinued due to adverse events. =0A=0AThe placebo discontinuatio= n rate was 1%. =0A=0AEven at 9 mg, only 2.9% of people dropped out. Compare= that to semaglutide and tirzepatide, which typically see 4 to 7% discontin= uation rates.=0A=0ASurvodutide had a rougher Phase 2 run. =0A=0AAbout 66% o= f people experienced nausea, 49% had diarrhea, and 41% had vomiting. =0A=0A= Discontinuation was 20 to 24%, mostly during rapid bi-weekly dose escalatio= n. When Phase 3 switched to a slower four-week titration, serious adverse e= vents actually dropped below placebo levels.=0A=0ASo which one is better? I= t depends on what you need. =0A=0AIf liver fat reduction and boosting your = metabolism are the priorities, mazdutide is probably the move. If you strug= gle more with appetite and want a little extra energy expenditure beyond wh= at semaglutide gives you, survodutide might be the better fit.=0A=0APersona= lly, I'd probably lean toward mazdutide. =0A=0AMy appetite isn't completely= out of control. I'd want more of that energy expenditure and liver fat ben= efit.=0A=0A=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94= =E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2= =80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80= =94=E2=80=94=E2=80=94=E2=80=94=0A=0A**Dosing **=0A=0AMazdutide is a once-we= ekly subcutaneous injection. =0A=0AThe approved doses in China are 4 mg and= 6 mg per week. =0A=0AThe titration protocol starts at 2 mg, then moves to = 4 mg, then to 6 mg, with about four weeks between each step. =0A=0AThe 9 mg= dose is the highest studied in China's GLORY-2 trial. The US is evaluating= doses up to 16 mg.=0A=0ASurvodutide is also once weekly. Phase 3 target do= ses are 3.6 mg and 6.0 mg. =0A=0APhase 2 used aggressive bi-weekly escalati= on and it caused high discontinuation. =0A=0APhase 3 redesigned the protoc= ol with slower four-week titration intervals, dose flexibility, and the opt= ion to pause and restart if GI side effects become intolerable.=0A=0AIf you= 're just starting out with either compound, 1 to 2 mg per week is a reasona= ble place to begin. See how your body responds. Scale from there. And give = yourself at least four weeks at each dose before moving up.=0A=0AIf you're = coming from retatrutide, you'll likely need to scale down your reta dose be= fore introducing either of these. They hit the same GLP-1 pathway but the g= lucagon agonism is going to feel different from the GIP component you're us= ed to.=0A=0A**People who escalate every four weeks instead of every two wee= ks are far more compliant and much better able to stay on the compound long= term. Don't rush the titration. Slow and steady wins here.**=0A=0AOne more= thing on dosing. I always prefer to split my weekly total across 2 to 3 in= jections rather than do it all at once. =0A=0AThis is something I do with r= etatrutide and would do with survodutide or mazdutide as well. =0A=0ASplitt= ing the dose spreads out the peptide exposure over the week. You get more s= table blood levels instead of one big spike. =0A=0AAnd in my experience, si= de effects are dramatically reduced when you do it this way. If your weekly= dose is 6 mg, try doing 2 mg on Monday, 2 mg on Wednesday, and 2 mg on Fri= day. =0A=0AYou'll likely tolerate it much better than slamming the full 6 m= g in one shot.=0A=0A=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94= =E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2= =80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80= =94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=0A=0A**Final Thoughts**=0A=0ASurvod= utide and mazdutide represent a new category in the GLP-1 world. =0A=0AThey= 're not retatrutide. But they're not far off. And they fill important gaps = that tirzepatide and semaglutide can't address.=0A=0AWhether you use them a= s a primary GLP-1, an alternative for people who don't tolerate retatrutide= well, or a rotation compound to maintain receptor sensitivity, I think the= y're worth researching.=0A=0ARemember to check out the video for the full b= reakdown.=0A=0AAs always, thank your support! =0A=0ABest,=0A=0AHunter Willi= ams =0A=0A=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94= =E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2= =80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80=94=E2=80= =94=E2=80=94=E2=80=94=E2=80=94=0A=0A**Further Reading**=0A=0A* [GLORY-1 Tri= al (Mazdutide Phase 3, NEJM)](https://www.nejm.org/doi/full/10.1056/NEJMoa2= 411528) =0A=0A* [GLORY-2 Results (Mazdutide 9mg)](https://www.prnewswire.co= m/news-releases/mazdutide-9-mg-achieves-up-to-20-1-weight-loss-in-chinese-a= dults-with-obesity-glory-2-study-meets-primary-and-all-key-secondary-endpoi= nts-302620471.html)=0A=0A* [DREAMS-1 & DREAMS-2 Results (Mazdutide in T2D, = Nature)](https://www.prnewswire.com/news-releases/nature--two-phase-3-clini= cal-results-of-mazdutide-glp-1gcg-dual-receptor-agonist-in-chinese-adults-w= ith-type-2-diabetes-have-been-back-to-back-published-in-nature-302644606.ht= ml)=0A=0A* [Survodutide FDA Breakthrough Therapy & LIVERAGE Phase 3 Trials]= (https://www.boehringer-ingelheim.com/human-health/metabolic-diseases/survo= dutide-us-fda-breakthrough-therapy-phase-3-trials-mash) =0A=0A* [SYNCHRONIZ= E Phase 3 Obesity Trials (Survodutide)](https://www.boehringer-ingelheim.co= m/human-health/metabolic-diseases/phase-3-studies-survodutide-obesity-and-o= verweight)=0A=0A* [SYNCHRONIZE-CVOT Design (Survodutide Cardiovascular Outc= omes)](https://www.sciencedirect.com/science/article/pii/S2213177924006620)= =0A=0A* [Mazdutide Clinical Trials Overview](https://www.findhonestcare.com= /metabolic-innovations/mazdutide/clinical-trials/)=0A=0A* [Survodutide Clin= ical Overview](https://www.findhonestcare.com/metabolic-innovations/survodu= tide/)=0A=0A=0A=E2=80=94=E2=80=94=E2=80=94=0A=0AYou are reading a plain tex= t version of this post. For the best experience, copy and paste this link i= n your browser to view the post online:=0Ahttps://huntershealthhacks.beehii= v.com/p/the-next-wave-of-glp-1s-is-coming --4ERMwaIzTiCgGBekZQbqtg Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: quoted-printable The Next Wave of GLP-1s Is Coming
<= div style=3D"display:none;max-height:0px;overflow:hidden;"> New video is li= ve!  ‌ ‌ ‌ ‌ ‌ = ‌ ‌ ‌ ‌ ‌ ‌= 60;‌ ‌ ‌ ‌ ‌ ‌=  ‌ ‌ ‌ ‌ ‌ R= 04; ‌ ‌ ‌ ‌ ‌ &= #8204; ‌ ‌ ‌ ‌ ‌= 0;‌ ‌ ‌ ‌ ‌ ‌&= #160;‌ ‌ ‌ ‌ ‌ ̴= 4; ‌ ‌ ‌ ‌ ‌ &#= 8204; ‌ ‌ ‌ ‌ ‌ = ;‌ ‌ ‌ ‌ ‌ ‌&#= 160;‌ ‌ ‌ ‌ ‌ ‌= ; ‌ ‌ ‌ ‌ ‌ = 204; ‌ ‌ ‌ ‌ ‌ = ‌ ‌ ‌ ‌ ‌ ‌= 60;‌ ‌ ‌ ‌ ‌ ‌=  ‌ ‌ ‌ ‌ ‌ R= 04; ‌ ‌ ‌ ‌ ‌ &= #8204; ‌ ‌ ‌ ‌ ‌= 0;‌ ‌ ‌ ‌ ‌ ‌&= #160;‌ ‌ ‌ ‌ ‌ ̴= 4; ‌ ‌ ‌ ‌ ‌ &#= 8204; ‌ ‌ ‌ ‌ ‌ = ;‌ ‌ ‌ ‌ ‌ ‌&#= 160;‌ ‌ ‌ ‌ ‌ ‌= ; ‌ ‌ ‌ ‌ ‌ = 204; ‌ ‌ ‌ ‌ ‌ = ‌ ‌ ‌ ‌ ‌ ‌= 60;‌ ‌ ‌ ‌ ‌ ‌=  ‌ ‌ ‌ ‌ ‌ R= 04; ‌ ‌ ‌ ‌ ‌ &= #8204; ‌ ‌ ‌ ‌ ‌= 0;‌ ‌ ‌ ‌ ‌ ‌&= #160;‌ ‌ ‌ ‌ ‌ ̴= 4; ‌ ‌ ‌ ‌
=

Dose

Trial Duration

=

Mazdutide

<= td class=3D"table-c" width=3D"16%" valign=3D"top" style=3D"border-bottom-wi= dth:1px;border-left-width:1px;border-right-width:1px;border-top-width:1px;p= adding-bottom:5px;padding-top:5px;">

~14%

<= td class=3D"table-c" width=3D"16%" valign=3D"top" style=3D"border-bottom-wi= dth:1px;border-left-width:1px;border-right-width:1px;border-top-width:1px;p= adding-bottom:5px;padding-top:5px;">

Survodutide

= =

Mazdutide is a synthetic analog of oxyntomodulin.

= = <= td class=3D"dd" align=3D"left" style=3D"padding:0px 15px;text-align:left;wo= rd-break:break-word;">

The heart rate increase with mazdutide was only abou= t 2.6 beats per minute at week 48.

<= td align=3D"center" valign=3D"top" style=3D"font-size:0px;line-height:0px;p= adding:30px 0px 30px;" class=3D"dd">

March 31, 2026   |   Read online

The Next Wave of GLP-1s Is Coming

New video is live!=

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Happy Tuesday!

There are two peptides quietly = making waves in the clinical space that will demand all of our attention ov= er the next 24 months.

They= don't work like semaglutide, they don't work like tirzepatide, and= the clinical data is turning heads.

I just dropped a brand new video breaking down survodutide and maz= dutide.

 
=
=

Survodutide & Maz= dutide | The GLP-1/Glucagon Duo That Could Rival Reta

The Hunter Williams Podcast =C2=B7 Episode

open.spotify.c= om/episode/2IADOstRyI6FrZlNHriPJB?si=3DRrUyDtoqTuqGt3-NERu-Ww

 

Today=E2=80=99s email wi= ll be a written email of the video and how these two peptides wlll be chang= ing the game.

Let's get= into it.

 

Background

It was originally developed by E= li Lilly and licensed to Innovent Biologics for development and commerciali= zation in China.

Lilly is= handling the US development separately. In June 2025, it became the world&= #39;s first approved GLP-1/glucagon receptor agonist when China greenlit it= under the brand name Xinermei for weight management.

It then received a second approval in September = 2025 for glycemic control in adults with type 2 diabetes. US trials are cur= rently in Phase 2, and FDA approval is estimated around 2028 to 2029.

Survodutide is a 29-amino acid pe= ptide co-invented by Boehringer Ingelheim and Zealand Pharma. It has not be= en approved anywhere yet. But it holds FDA Breakthrough Therapy designation= s specifically for MASH.

Th= e Phase 3 SYNCHRONIZE trials are fully enrolled with over 1,400 patients, a= nd results are expected in the first half of 2026.

=
 

H= ow They Work

You already= know how GLP-1 agonism works. It suppresses appetite, delays gastric empty= ing, stimulates insulin secretion, and inhibits glucagon release from alpha= cells.

Hundreds of million= s of people have used GLP-1 peptides at this point.

Survodutide and mazdutide are different because the= y have a glucagon receptor agonist on one side of the molecule.

=

Glucagon agonism increases energy expe= nditure. Studies show that acute glucagon infusion increases caloric expend= iture by about 200 calories per day.

This happens through hepatic fuel cycling, FGF-21 thermogenesis, = and brown fat adipocyte activation. Basically, your body burns more calorie= s at rest.

Then there's = the liver fat component. Glucagon activation increases hepatic beta-oxidati= on. It suppresses de novo lipogenesis. And it restores mitochondrial functi= on.

These are effects that = GLP-1 agonism alone cannot replicate.

When glucagon agonism is combined with GLP-1 agonism in a single= molecule, the GLP-1 component counterbalances the glucose-raising effect o= f glucagon.

No increased r= isk of hyperglycemia has been observed in trials of either compound.=

 

The Benefits

The weight loss numbers are impressive, but honestly, the metabolic = benefits beyond fat loss are what make these compounds exciting.

=

Mazdutide at 6 mg per week showed an 8= 0% reduction in liver fat in patients with baseline hepatic steatosis.

Survodutide showed 62% MASH res= olution versus just 14% on placebo, with 67% of patients achieving greater = than 30% liver fat reduction.

Both peptides also reduce waist circumference and systolic blood pressur= e.

Improvements in triglycer= ides, LDL cholesterol, and uric acid have been documented across multiple t= rials.

Survodutide showed d= ramatic reductions in liver enzymes (ALT and AST), reflecting reduced liver= inflammation.

Mazdutide pro= duced A1C reductions of approximately 1.5-2.15%.

Compare that to what I typically see with retatrutide, which is usu= ally 5 to 10 beats per minute within a few weeks.

=
 

C= linical Results Compared to Tirzepatide and Retatrutide

Here's where we stack these up against = the compounds you already know. I put together a quick comparison chart so = you can see it all at a glance.

Compound

Receptors

Max Weight Loss

Liver Fat Reduction

Semaglutide

2.4 mg/wk

GLP-1

68 weeks

~16%

Moderate

6 mg/wk

GLP-1 + Glucagon

=

48 weeks

~80%

=

4.8 mg/wk

GLP-1 + Glucagon

46 weeks

=

~18.7%

~67% (>30% reduction)=

Mazdutide

9= mg/wk

= GLP-1 + Glucagon

60 weeks

~20% (non-diabetics)

Not yet reported

Mazdutide<= /span>

16 mg/wk

GLP-1 + Gluc= agon

20 weeks

~21%

Not yet reported

Tirzepatide

15 mg/wk

GLP-1 + GIP

72 weeks

~22%

Moderate

Retatrutide

12 mg/wk

GLP-1 + GIP + Glucagon

48 weeks

=

~24%

<= p style=3D"mso-line-height-alt:150.0%;padding:0px;text-align:left;word-brea= k:break-word;">~82-86%

When you compare mazdutide a= nd tirzepatide at similar dosing, you're getting pretty comparable fat = loss numbers.

Tirzepatide h= its GLP-1 and GIP. Mazdutide hits GLP-1 and glucagon. Similar weight loss, = but mazdutide provides liver fat and energy expenditure benefits that GIP a= gonism simply does not.

Reta= trutide is still king on paper. It hits all three receptors and delivers th= e most weight loss.

But sur= vodutide and mazdutide are not far behind. And for people who need an alter= native, or who want to cycle compounds to maintain receptor sensitivity, th= ese fill a real gap.

Phase 3 redesigned the protocol with slower four-wee= k titration intervals, dose flexibility, and the option to pause and restar= t if GI side effects become intolerable.

= <= td class=3D"dd" align=3D"left" style=3D"padding:0px 15px;text-align:left;wo= rd-break:break-word;">

Splitting the dose spreads out the peptide exposure = over the week. You get more stable blood levels instead of one big spike. <= /span>

=
 

They're Not the Same

You see these two listed toge= ther as GLP-1/glucagon agonists and assume they're interchangeable. The= y're not.

Survodutide is= GLP-1 dominant.

The appr= oximate ratio is about 8:1, GLP-1 to glucagon. Think of it as semaglutide w= ith a little glucagon cherry on top. You get strong appetite suppression wi= th a modest boost in energy expenditure.

Mazdutide is almost 50/50. The ratio of GLP-1 to glucagon ago= nism is roughly balanced, though it slightly favors glucagon.

That means more direct hepatic fat oxida= tion. More energy expenditure increase. And it explains why mazdutide is so= good at reducing liver fat.

This difference shows up in the tolerability data, too.

Mazdutide had a remarkably clean tolerability= profile. Only 0.5% of people at the 6 mg dose discontinued due to adverse = events.

The placebo discont= inuation rate was 1%.

Even = at 9 mg, only 2.9% of people dropped out. Compare that to semaglutide and t= irzepatide, which typically see 4 to 7% discontinuation rates.

Survodutide had a rougher Phase 2 run. <= /span>

About 66% of people experien= ced nausea, 49% had diarrhea, and 41% had vomiting.

Discontinuation was 20 to 24%, mostly during rapid= bi-weekly dose escalation. When Phase 3 switched to a slower four-week tit= ration, serious adverse events actually dropped below placebo levels.

So which one is better? It depend= s on what you need.

If live= r fat reduction and boosting your metabolism are the priorities, mazdutide = is probably the move. If you struggle more with appetite and want a little = extra energy expenditure beyond what semaglutide gives you, survodutide mig= ht be the better fit.

Person= ally, I'd probably lean toward mazdutide.

My appetite isn't completely out of control. I'd= want more of that energy expenditure and liver fat benefit.

 

Dosing

Mazdu= tide is a once-weekly subcutaneous injection.

The approved doses in China are 4 mg and 6 mg per week. =

The titration protocol star= ts at 2 mg, then moves to 4 mg, then to 6 mg, with about four weeks between= each step.

The 9 mg dose = is the highest studied in China's GLORY-2 trial. The US is evaluating d= oses up to 16 mg.

Survodut= ide is also once weekly. Phase 3 target doses are 3.6 mg and 6.0 mg.

Phase 2 used aggressive bi-weekly= escalation and it caused high discontinuation.

If you're just starting out with either compound, 1 to 2 = mg per week is a reasonable place to begin. See how your body responds. Sca= le from there. And give yourself at least four weeks at each dose before mo= ving up.

If you're comin= g from retatrutide, you'll likely need to scale down your reta dose bef= ore introducing either of these. They hit the same GLP-1 pathway but the gl= ucagon agonism is going to feel different from the GIP component you're= used to.

People who esca= late every four weeks instead of every two weeks are far more compliant and= much better able to stay on the compound long term. Don't rush the tit= ration. Slow and steady wins here.

One more thing on dosing. I always prefer to split my weekly tot= al across 2 to 3 injections rather than do it all at once.

This is something I do with retatrutide and= would do with survodutide or mazdutide as well.

And in my experience, side e= ffects are dramatically reduced when you do it this way. If your weekly dos= e is 6 mg, try doing 2 mg on Monday, 2 mg on Wednesday, and 2 mg on Friday.=

You'll likely tolerate= it much better than slamming the full 6 mg in one shot.

 
Final Thoughts

Surv= odutide and mazdutide represent a new category in the GLP-1 world. <= /p>

They're not retatrutide. But th= ey're not far off. And they fill important gaps that tirzepatide and se= maglutide can't address.

Whether you use them as a primary GLP-1, an alternative for people who don= 't tolerate retatrutide well, or a rotation compound to maintain recept= or sensitivity, I think they're worth researching.

Remember to check out the video for the full bre= akdown.

As always, thank you= r support!

Best,

Hunter Williams

 

Further Reading

=
=
=
=
3D"ig"3D"yt"
3D""

Want more? Here=E2=80=99s how you= can work with me:

=F0=9F=91=89Join my private coaching group, The AXION C= ollective:

=F0=9F=91=89Try Zeroats, the = world=E2=80=99s first sugar-free, naturally flavored oatmeal:

<= /div>

=F0=9F=91=89G= et the Peptide Cheat Sheet:

<= /td>

=F0=9F=91=89A= ll my daily essentials on Amazon

=

=F0=9F=91= =89Get discounts on your favorite peptides and research chemicals:

=F0=9F=91=8910= % off the BEST workout supplements from Unmatched Supps (pre-workout, whey = protein, creatine, EAAs, electrolytes - use code HUNTERW at checkout):

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