u/Sea-Performer-71

Founder of a US-based research peptide vendor here. Launching our affiliate program and looking for creators to partner with.

What we're looking for:

Creators in the biohacking, longevity, nootropics, or recovery space. Follower count isn't the priority — audience fit is. If your followers are already deep in this space, you're who we want.

What we offer:

Percentage-based commission, real-time tracking portal, and product to try before you promote anything. All products are research use only — content needs to stay within that framing.

DM me with your platform and a quick description of your audience.

Founder of a US-based research peptide vendor here. Launching our affiliate program and looking for creators to partner with.

What we're looking for:

Creators in the biohacking, longevity, nootropics, or recovery space. Follower count isn't the priority — audience fit is. If your followers are already deep in this space, you're who we want.

What we offer:

Percentage-based commission, real-time tracking portal, and product to try before you promote anything. All products are research use only — content needs to stay within that framing.

DM me with your platform and a quick description of your audience.

Founder of a US-based research peptide vendor here. Launching our affiliate program and looking for creators to partner with.

What we're looking for:

Creators in the biohacking, longevity, nootropics, or recovery space. Follower count isn't the priority — audience fit is. If your followers are already deep in this space, you're who we want.

What we offer:

Percentage-based commission, real-time tracking portal, and product to try before you promote anything. All products are research use only — content needs to stay within that framing.

DM me with your platform and a quick description of your audience.

Founder of a US-based research peptide vendor here. Launching our affiliate program and looking for creators to partner with.

What we're looking for:

Creators in the biohacking, longevity, nootropics, or recovery space. Follower count isn't the priority — audience fit is. If your followers are already deep in this space, you're who we want.

What we offer:

Percentage-based commission, real-time tracking portal, and product to try before you promote anything. All products are research use only — content needs to stay within that framing.

DM me with your platform and a quick description of your audience.

Founder of a US-based research peptide vendor here. Launching our affiliate program and looking for creators to partner with.

What we're looking for:

Creators in the biohacking, longevity, nootropics, or recovery space. Follower count isn't the priority — audience fit is. If your followers are already deep in this space, you're who we want.

What we offer:

Percentage-based commission, real-time tracking portal, and product to try before you promote anything. All products are research use only — content needs to stay within that framing.

DM me with your platform and a quick description of your audience.

Founder of a US-based research peptide vendor here. Launching our affiliate program and looking for creators to partner with.

What we're looking for:

Creators in the biohacking, longevity, nootropics, or recovery space. Follower count isn't the priority — audience fit is. If your followers are already deep in this space, you're who we want.

What we offer:

Percentage-based commission, real-time tracking portal, and product to try before you promote anything. All products are research use only — content needs to stay within that framing.

DM me with your platform and a quick description of your audience.

Founder of a US-based research peptide vendor here. Launching our affiliate program and looking for creators to partner with.

What we're looking for:

Creators in the biohacking, longevity, nootropics, or recovery space. Follower count isn't the priority — audience fit is. If your followers are already deep in this space, you're who we want.

What we offer:

Percentage-based commission, real-time tracking portal, and product to try before you promote anything. All products are research use only — content needs to stay within that framing.

DM me with your platform and a quick description of your audience.

Pep-dose is a free, ad-free web app for tracking peptide protocols. The core is a dose tracker: pick a protocol from the built-in library (single peptides and blends) or enter your own parameters, set up a schedule with titration, maintenance, and off-cycle/washout phases, then log each dose as taken or skipped and watch your adherence and cycle progress over time.

It also has a reconstitution calculator that handles the BAC-water and syringe-unit math for you, plus a library of plain-language articles and dosing protocols where every claim links to the peer-reviewed source so you can verify it yourself instead of trusting a random forum post.

The web app is mobile-friendly — you can install it to your home screen and get dose reminders — and native iPhone/Android apps are coming. No ads, no paywall, no upsells; it's sponsor-supported, which is how it stays free.

Check it out at: https://pep-dose.com/

This isn't a "which drug wins" post. It's a breakdown of what the third receptor target does mechanistically, what the body composition data actually shows, and what questions are still open going into Phase 3.

​

​

The mechanism difference

​

​

Tirzepatide hits GLP-1 and GIP receptors. Retatrutide adds the glucagon receptor. That third target is the entire basis for the excitement around retatrutide, and it's worth understanding what glucagon receptor agonism actually does rather than treating it as a vague "more is better" addition.

​

Glucagon receptor activation drives several distinct effects: it promotes lipolysis (preferential fat oxidation over muscle catabolism), increases thermogenesis via brown and beige adipose tissue, and drives hepatic fatty acid oxidation. The net result is meaningfully higher energy expenditure compared to dual agonists, which is the likely explanation for why retatrutide's weight loss numbers are higher than tirzepatide's at comparable timepoints. At 48 weeks in Phase 2, retatrutide at 12 mg produced 24.2% mean weight loss. Tirzepatide's comparable figure from SURMOUNT-1 was 20.9% at 72 weeks.

​

​

The concern that comes with glucagon receptor agonism is also worth stating directly: glucagon is catabolic. It promotes hepatic glucose output and can lower circulating amino acids, which could reduce muscle protein synthesis. So there was a real question going into the body composition substudy about whether the glucagon component would worsen the lean mass ratio relative to other drugs.

​

​

What the Phase 2 body composition data actually showed

​

​

A substudy of the Phase 2 T2D trial, published in The Lancet Diabetes and Endocrinology in June 2025, used DEXA scanning to measure fat mass and lean mass changes separately across retatrutide doses. The key finding: the fat loss index (fat mass loss as a proportion of total weight loss) was 64.6% in a pooled analysis of the 4, 8, and 12 mg arms. That means lean mass comprised roughly 35.4% of total weight lost, a proportion the authors describe as consistent with other obesity treatments.

​

​

For comparison, tirzepatide's DEXA data from SURMOUNT showed fat mass decreasing 33.9% while lean mass decreased 10.9%.

​

​

The short version: despite the theoretical concern that glucagon agonism would worsen the lean to fat loss ratio, Phase 2 data suggests it didn't. The glucagon component appears to preferentially drive fat oxidation rather than muscle catabolism, which is what the preclinical models predicted.

​

​

https://www.sciencedirect.com/science/article/abs/pii/S2213858725000920

​

​

What's still unknown

​

​

The Phase 2 substudy was conducted in people with type 2 diabetes over 36 weeks. TRIUMPH-1 enrolled a broader obesity population over 80 weeks, with a subgroup extending to 104 weeks.

​

​

Full body composition data from TRIUMPH-1 has not been published. The questions that remain:

​

​

Does the favorable lean mass ratio hold at greater weight loss magnitudes? At 28% body weight reduction, the absolute lean mass lost is substantially larger than at 17%, even if the proportion is similar. For older patients or anyone with lower baseline lean mass, that absolute number matters independently of the ratio.

​

​

Bone mineral density. Significant weight loss of any kind can reduce bone density, and retatrutide has published no bone data yet. This is flagged as a secondary outcome in Phase 3 but results aren't available.

​

​

Head to head comparison. Every comparison between retatrutide and tirzepatide body composition data right now is cross-trial, meaning different populations, different durations, different study designs. A direct randomized comparison doesn't exist yet.

​

​

The GI side effect picture

​

​

Retatrutide's Phase 2 GI side effect rates were higher than tirzepatide's, almost certainly due to the glucagon component. Nausea, vomiting, and diarrhea occurred more frequently, particularly during dose escalation. Whether the titration schedule in Phase 3 mitigates this relative to Phase 2 is something the TRIUMPH data will clarify when it's fully published.

​

​

What to watch for

​

​

Full body composition secondary outcomes from TRIUMPH-1 are the most important near-term data point for anyone trying to evaluate retatrutide seriously. The headline weight loss numbers are out. The composition of that weight loss, particularly at the 80 and 104 week timepoints, will either confirm or complicate the Phase 2 picture. Bone mineral density data and outcomes in older adults will matter too, especially as the drug eventually gets used outside the clinical trial population.

This isn't a "which drug wins" post. It's a breakdown of what the third receptor target does mechanistically, what the body composition data actually shows, and what questions are still open going into Phase 3.

​

The mechanism difference

​

Tirzepatide hits GLP-1 and GIP receptors. Retatrutide adds the glucagon receptor. That third target is the entire basis for the excitement around retatrutide, and it's worth understanding what glucagon receptor agonism actually does rather than treating it as a vague "more is better" addition.

Glucagon receptor activation drives several distinct effects: it promotes lipolysis (preferential fat oxidation over muscle catabolism), increases thermogenesis via brown and beige adipose tissue, and drives hepatic fatty acid oxidation. The net result is meaningfully higher energy expenditure compared to dual agonists, which is the likely explanation for why retatrutide's weight loss numbers are higher than tirzepatide's at comparable timepoints. At 48 weeks in Phase 2, retatrutide at 12 mg produced 24.2% mean weight loss. Tirzepatide's comparable figure from SURMOUNT-1 was 20.9% at 72 weeks.

​

The concern that comes with glucagon receptor agonism is also worth stating directly: glucagon is catabolic. It promotes hepatic glucose output and can lower circulating amino acids, which could reduce muscle protein synthesis. So there was a real question going into the body composition substudy about whether the glucagon component would worsen the lean mass ratio relative to other drugs.

​

What the Phase 2 body composition data actually showed

​

A substudy of the Phase 2 T2D trial, published in The Lancet Diabetes and Endocrinology in June 2025, used DEXA scanning to measure fat mass and lean mass changes separately across retatrutide doses. The key finding: the fat loss index (fat mass loss as a proportion of total weight loss) was 64.6% in a pooled analysis of the 4, 8, and 12 mg arms. That means lean mass comprised roughly 35.4% of total weight lost, a proportion the authors describe as consistent with other obesity treatments.

​

For comparison, tirzepatide's DEXA data from SURMOUNT showed fat mass decreasing 33.9% while lean mass decreased 10.9%.

​

The short version: despite the theoretical concern that glucagon agonism would worsen the lean to fat loss ratio, Phase 2 data suggests it didn't. The glucagon component appears to preferentially drive fat oxidation rather than muscle catabolism, which is what the preclinical models predicted.

​

https://www.sciencedirect.com/science/article/abs/pii/S2213858725000920

​

What's still unknown

​

The Phase 2 substudy was conducted in people with type 2 diabetes over 36 weeks. TRIUMPH-1 enrolled a broader obesity population over 80 weeks, with a subgroup extending to 104 weeks.

​

Full body composition data from TRIUMPH-1 has not been published. The questions that remain:

​

Does the favorable lean mass ratio hold at greater weight loss magnitudes? At 28% body weight reduction, the absolute lean mass lost is substantially larger than at 17%, even if the proportion is similar. For older patients or anyone with lower baseline lean mass, that absolute number matters independently of the ratio.

​

Bone mineral density. Significant weight loss of any kind can reduce bone density, and retatrutide has published no bone data yet. This is flagged as a secondary outcome in Phase 3 but results aren't available.

​

Head to head comparison. Every comparison between retatrutide and tirzepatide body composition data right now is cross-trial, meaning different populations, different durations, different study designs. A direct randomized comparison doesn't exist yet.

​

The GI side effect picture

​

Retatrutide's Phase 2 GI side effect rates were higher than tirzepatide's, almost certainly due to the glucagon component. Nausea, vomiting, and diarrhea occurred more frequently, particularly during dose escalation. Whether the titration schedule in Phase 3 mitigates this relative to Phase 2 is something the TRIUMPH data will clarify when it's fully published.

​

What to watch for

​

Full body composition secondary outcomes from TRIUMPH-1 are the most important near-term data point for anyone trying to evaluate retatrutide seriously. The headline weight loss numbers are out. The composition of that weight loss, particularly at the 80 and 104 week timepoints, will either confirm or complicate the Phase 2 picture. Bone mineral density data and outcomes in older adults will matter too, especially as the drug eventually gets used outside the clinical trial population.

​

More stories at r/PeptideTides

This isn't a "which drug wins" post. It's a breakdown of what the third receptor target does mechanistically, what the body composition data actually shows, and what questions are still open going into Phase 3.

​

The mechanism difference

​

Tirzepatide hits GLP-1 and GIP receptors. Retatrutide adds the glucagon receptor. That third target is the entire basis for the excitement around retatrutide, and it's worth understanding what glucagon receptor agonism actually does rather than treating it as a vague "more is better" addition.

Glucagon receptor activation drives several distinct effects: it promotes lipolysis (preferential fat oxidation over muscle catabolism), increases thermogenesis via brown and beige adipose tissue, and drives hepatic fatty acid oxidation. The net result is meaningfully higher energy expenditure compared to dual agonists, which is the likely explanation for why retatrutide's weight loss numbers are higher than tirzepatide's at comparable timepoints. At 48 weeks in Phase 2, retatrutide at 12 mg produced 24.2% mean weight loss. Tirzepatide's comparable figure from SURMOUNT-1 was 20.9% at 72 weeks.

​

The concern that comes with glucagon receptor agonism is also worth stating directly: glucagon is catabolic. It promotes hepatic glucose output and can lower circulating amino acids, which could reduce muscle protein synthesis. So there was a real question going into the body composition substudy about whether the glucagon component would worsen the lean mass ratio relative to other drugs.

​

What the Phase 2 body composition data actually showed

​

A substudy of the Phase 2 T2D trial, published in The Lancet Diabetes and Endocrinology in June 2025, used DEXA scanning to measure fat mass and lean mass changes separately across retatrutide doses. The key finding: the fat loss index (fat mass loss as a proportion of total weight loss) was 64.6% in a pooled analysis of the 4, 8, and 12 mg arms. That means lean mass comprised roughly 35.4% of total weight lost, a proportion the authors describe as consistent with other obesity treatments.

​

For comparison, tirzepatide's DEXA data from SURMOUNT showed fat mass decreasing 33.9% while lean mass decreased 10.9%.

​

The short version: despite the theoretical concern that glucagon agonism would worsen the lean to fat loss ratio, Phase 2 data suggests it didn't. The glucagon component appears to preferentially drive fat oxidation rather than muscle catabolism, which is what the preclinical models predicted.

​

https://www.sciencedirect.com/science/article/abs/pii/S2213858725000920

​

What's still unknown

​

The Phase 2 substudy was conducted in people with type 2 diabetes over 36 weeks. TRIUMPH-1 enrolled a broader obesity population over 80 weeks, with a subgroup extending to 104 weeks.

​

Full body composition data from TRIUMPH-1 has not been published. The questions that remain:

​

Does the favorable lean mass ratio hold at greater weight loss magnitudes? At 28% body weight reduction, the absolute lean mass lost is substantially larger than at 17%, even if the proportion is similar. For older patients or anyone with lower baseline lean mass, that absolute number matters independently of the ratio.

​

Bone mineral density. Significant weight loss of any kind can reduce bone density, and retatrutide has published no bone data yet. This is flagged as a secondary outcome in Phase 3 but results aren't available.

​

Head to head comparison. Every comparison between retatrutide and tirzepatide body composition data right now is cross-trial, meaning different populations, different durations, different study designs. A direct randomized comparison doesn't exist yet.

​

The GI side effect picture

​

Retatrutide's Phase 2 GI side effect rates were higher than tirzepatide's, almost certainly due to the glucagon component. Nausea, vomiting, and diarrhea occurred more frequently, particularly during dose escalation. Whether the titration schedule in Phase 3 mitigates this relative to Phase 2 is something the TRIUMPH data will clarify when it's fully published.

​

What to watch for

​

Full body composition secondary outcomes from TRIUMPH-1 are the most important near-term data point for anyone trying to evaluate retatrutide seriously. The headline weight loss numbers are out. The composition of that weight loss, particularly at the 80 and 104 week timepoints, will either confirm or complicate the Phase 2 picture. Bone mineral density data and outcomes in older adults will matter too, especially as the drug eventually gets used outside the clinical trial population.

​

More stories at r/PeptideTides

This isn't a "which drug wins" post. It's a breakdown of what the third receptor target does mechanistically, what the body composition data actually shows, and what questions are still open going into Phase 3.

​

​

The mechanism difference

​

​

Tirzepatide hits GLP-1 and GIP receptors. Retatrutide adds the glucagon receptor. That third target is the entire basis for the excitement around retatrutide, and it's worth understanding what glucagon receptor agonism actually does rather than treating it as a vague "more is better" addition.

​

Glucagon receptor activation drives several distinct effects: it promotes lipolysis (preferential fat oxidation over muscle catabolism), increases thermogenesis via brown and beige adipose tissue, and drives hepatic fatty acid oxidation. The net result is meaningfully higher energy expenditure compared to dual agonists, which is the likely explanation for why retatrutide's weight loss numbers are higher than tirzepatide's at comparable timepoints. At 48 weeks in Phase 2, retatrutide at 12 mg produced 24.2% mean weight loss. Tirzepatide's comparable figure from SURMOUNT-1 was 20.9% at 72 weeks.

​

​

The concern that comes with glucagon receptor agonism is also worth stating directly: glucagon is catabolic. It promotes hepatic glucose output and can lower circulating amino acids, which could reduce muscle protein synthesis. So there was a real question going into the body composition substudy about whether the glucagon component would worsen the lean mass ratio relative to other drugs.

​

​

What the Phase 2 body composition data actually showed

​

​

A substudy of the Phase 2 T2D trial, published in The Lancet Diabetes and Endocrinology in June 2025, used DEXA scanning to measure fat mass and lean mass changes separately across retatrutide doses. The key finding: the fat loss index (fat mass loss as a proportion of total weight loss) was 64.6% in a pooled analysis of the 4, 8, and 12 mg arms. That means lean mass comprised roughly 35.4% of total weight lost, a proportion the authors describe as consistent with other obesity treatments.

​

​

For comparison, tirzepatide's DEXA data from SURMOUNT showed fat mass decreasing 33.9% while lean mass decreased 10.9%.

​

​

The short version: despite the theoretical concern that glucagon agonism would worsen the lean to fat loss ratio, Phase 2 data suggests it didn't. The glucagon component appears to preferentially drive fat oxidation rather than muscle catabolism, which is what the preclinical models predicted.

​

​

https://www.sciencedirect.com/science/article/abs/pii/S2213858725000920

​

​

What's still unknown

​

​

The Phase 2 substudy was conducted in people with type 2 diabetes over 36 weeks. TRIUMPH-1 enrolled a broader obesity population over 80 weeks, with a subgroup extending to 104 weeks.

​

​

Full body composition data from TRIUMPH-1 has not been published. The questions that remain:

​

​

Does the favorable lean mass ratio hold at greater weight loss magnitudes? At 28% body weight reduction, the absolute lean mass lost is substantially larger than at 17%, even if the proportion is similar. For older patients or anyone with lower baseline lean mass, that absolute number matters independently of the ratio.

​

​

Bone mineral density. Significant weight loss of any kind can reduce bone density, and retatrutide has published no bone data yet. This is flagged as a secondary outcome in Phase 3 but results aren't available.

​

​

Head to head comparison. Every comparison between retatrutide and tirzepatide body composition data right now is cross-trial, meaning different populations, different durations, different study designs. A direct randomized comparison doesn't exist yet.

​

​

The GI side effect picture

​

​

Retatrutide's Phase 2 GI side effect rates were higher than tirzepatide's, almost certainly due to the glucagon component. Nausea, vomiting, and diarrhea occurred more frequently, particularly during dose escalation. Whether the titration schedule in Phase 3 mitigates this relative to Phase 2 is something the TRIUMPH data will clarify when it's fully published.

​

​

What to watch for

​

​

Full body composition secondary outcomes from TRIUMPH-1 are the most important near-term data point for anyone trying to evaluate retatrutide seriously. The headline weight loss numbers are out. The composition of that weight loss, particularly at the 80 and 104 week timepoints, will either confirm or complicate the Phase 2 picture. Bone mineral density data and outcomes in older adults will matter too, especially as the drug eventually gets used outside the clinical trial population.

​

​

More stories at r/PeptideTides

​

​

This isn't a "which drug wins" post. It's a breakdown of what the third receptor target does mechanistically, what the body composition data actually shows, and what questions are still open going into Phase 3.

​

The mechanism difference

​

Tirzepatide hits GLP-1 and GIP receptors. Retatrutide adds the glucagon receptor. That third target is the entire basis for the excitement around retatrutide, and it's worth understanding what glucagon receptor agonism actually does rather than treating it as a vague "more is better" addition.

Glucagon receptor activation drives several distinct effects: it promotes lipolysis (preferential fat oxidation over muscle catabolism), increases thermogenesis via brown and beige adipose tissue, and drives hepatic fatty acid oxidation. The net result is meaningfully higher energy expenditure compared to dual agonists, which is the likely explanation for why retatrutide's weight loss numbers are higher than tirzepatide's at comparable timepoints. At 48 weeks in Phase 2, retatrutide at 12 mg produced 24.2% mean weight loss. Tirzepatide's comparable figure from SURMOUNT-1 was 20.9% at 72 weeks.

​

The concern that comes with glucagon receptor agonism is also worth stating directly: glucagon is catabolic. It promotes hepatic glucose output and can lower circulating amino acids, which could reduce muscle protein synthesis. So there was a real question going into the body composition substudy about whether the glucagon component would worsen the lean mass ratio relative to other drugs.

​

What the Phase 2 body composition data actually showed

​

A substudy of the Phase 2 T2D trial, published in The Lancet Diabetes and Endocrinology in June 2025, used DEXA scanning to measure fat mass and lean mass changes separately across retatrutide doses. The key finding: the fat loss index (fat mass loss as a proportion of total weight loss) was 64.6% in a pooled analysis of the 4, 8, and 12 mg arms. That means lean mass comprised roughly 35.4% of total weight lost, a proportion the authors describe as consistent with other obesity treatments.

​

For comparison, tirzepatide's DEXA data from SURMOUNT showed fat mass decreasing 33.9% while lean mass decreased 10.9%.

​

The short version: despite the theoretical concern that glucagon agonism would worsen the lean to fat loss ratio, Phase 2 data suggests it didn't. The glucagon component appears to preferentially drive fat oxidation rather than muscle catabolism, which is what the preclinical models predicted.

​

https://www.sciencedirect.com/science/article/abs/pii/S2213858725000920

​

What's still unknown

​

The Phase 2 substudy was conducted in people with type 2 diabetes over 36 weeks. TRIUMPH-1 enrolled a broader obesity population over 80 weeks, with a subgroup extending to 104 weeks.

​

Full body composition data from TRIUMPH-1 has not been published. The questions that remain:

​

Does the favorable lean mass ratio hold at greater weight loss magnitudes? At 28% body weight reduction, the absolute lean mass lost is substantially larger than at 17%, even if the proportion is similar. For older patients or anyone with lower baseline lean mass, that absolute number matters independently of the ratio.

​

Bone mineral density. Significant weight loss of any kind can reduce bone density, and retatrutide has published no bone data yet. This is flagged as a secondary outcome in Phase 3 but results aren't available.

​

Head to head comparison. Every comparison between retatrutide and tirzepatide body composition data right now is cross-trial, meaning different populations, different durations, different study designs. A direct randomized comparison doesn't exist yet.

​

The GI side effect picture

​

Retatrutide's Phase 2 GI side effect rates were higher than tirzepatide's, almost certainly due to the glucagon component. Nausea, vomiting, and diarrhea occurred more frequently, particularly during dose escalation. Whether the titration schedule in Phase 3 mitigates this relative to Phase 2 is something the TRIUMPH data will clarify when it's fully published.

​

What to watch for

​

Full body composition secondary outcomes from TRIUMPH-1 are the most important near-term data point for anyone trying to evaluate retatrutide seriously. The headline weight loss numbers are out. The composition of that weight loss, particularly at the 80 and 104 week timepoints, will either confirm or complicate the Phase 2 picture. Bone mineral density data and outcomes in older adults will matter too, especially as the drug eventually gets used outside the clinical trial population.

​

More stories at r/PeptideTides

This isn't a "which drug wins" post. It's a breakdown of what the third receptor target does mechanistically, what the body composition data actually shows, and what questions are still open going into Phase 3.

​

​

The mechanism difference

​

​

Tirzepatide hits GLP-1 and GIP receptors. Retatrutide adds the glucagon receptor. That third target is the entire basis for the excitement around retatrutide, and it's worth understanding what glucagon receptor agonism actually does rather than treating it as a vague "more is better" addition.

​

Glucagon receptor activation drives several distinct effects: it promotes lipolysis (preferential fat oxidation over muscle catabolism), increases thermogenesis via brown and beige adipose tissue, and drives hepatic fatty acid oxidation. The net result is meaningfully higher energy expenditure compared to dual agonists, which is the likely explanation for why retatrutide's weight loss numbers are higher than tirzepatide's at comparable timepoints. At 48 weeks in Phase 2, retatrutide at 12 mg produced 24.2% mean weight loss. Tirzepatide's comparable figure from SURMOUNT-1 was 20.9% at 72 weeks.

​

​

The concern that comes with glucagon receptor agonism is also worth stating directly: glucagon is catabolic. It promotes hepatic glucose output and can lower circulating amino acids, which could reduce muscle protein synthesis. So there was a real question going into the body composition substudy about whether the glucagon component would worsen the lean mass ratio relative to other drugs.

​

​

What the Phase 2 body composition data actually showed

​

​

A substudy of the Phase 2 T2D trial, published in The Lancet Diabetes and Endocrinology in June 2025, used DEXA scanning to measure fat mass and lean mass changes separately across retatrutide doses. The key finding: the fat loss index (fat mass loss as a proportion of total weight loss) was 64.6% in a pooled analysis of the 4, 8, and 12 mg arms. That means lean mass comprised roughly 35.4% of total weight lost, a proportion the authors describe as consistent with other obesity treatments.

​

​

For comparison, tirzepatide's DEXA data from SURMOUNT showed fat mass decreasing 33.9% while lean mass decreased 10.9%.

​

​

The short version: despite the theoretical concern that glucagon agonism would worsen the lean to fat loss ratio, Phase 2 data suggests it didn't. The glucagon component appears to preferentially drive fat oxidation rather than muscle catabolism, which is what the preclinical models predicted.

​

​

https://www.sciencedirect.com/science/article/abs/pii/S2213858725000920

​

​

What's still unknown

​

​

The Phase 2 substudy was conducted in people with type 2 diabetes over 36 weeks. TRIUMPH-1 enrolled a broader obesity population over 80 weeks, with a subgroup extending to 104 weeks.

​

​

Full body composition data from TRIUMPH-1 has not been published. The questions that remain:

​

​

Does the favorable lean mass ratio hold at greater weight loss magnitudes? At 28% body weight reduction, the absolute lean mass lost is substantially larger than at 17%, even if the proportion is similar. For older patients or anyone with lower baseline lean mass, that absolute number matters independently of the ratio.

​

​

Bone mineral density. Significant weight loss of any kind can reduce bone density, and retatrutide has published no bone data yet. This is flagged as a secondary outcome in Phase 3 but results aren't available.

​

​

Head to head comparison. Every comparison between retatrutide and tirzepatide body composition data right now is cross-trial, meaning different populations, different durations, different study designs. A direct randomized comparison doesn't exist yet.

​

​

The GI side effect picture

​

​

Retatrutide's Phase 2 GI side effect rates were higher than tirzepatide's, almost certainly due to the glucagon component. Nausea, vomiting, and diarrhea occurred more frequently, particularly during dose escalation. Whether the titration schedule in Phase 3 mitigates this relative to Phase 2 is something the TRIUMPH data will clarify when it's fully published.

​

​

What to watch for

​

​

Full body composition secondary outcomes from TRIUMPH-1 are the most important near-term data point for anyone trying to evaluate retatrutide seriously. The headline weight loss numbers are out. The composition of that weight loss, particularly at the 80 and 104 week timepoints, will either confirm or complicate the Phase 2 picture. Bone mineral density data and outcomes in older adults will matter too, especially as the drug eventually gets used outside the clinical trial population.

​

​

More stories at r/PeptideTides

​

​

This isn't a "which drug wins" post. It's a breakdown of what the third receptor target does mechanistically, what the body composition data actually shows, and what questions are still open going into Phase 3.

​

The mechanism difference

​

Tirzepatide hits GLP-1 and GIP receptors. Retatrutide adds the glucagon receptor. That third target is the entire basis for the excitement around retatrutide, and it's worth understanding what glucagon receptor agonism actually does rather than treating it as a vague "more is better" addition.

Glucagon receptor activation drives several distinct effects: it promotes lipolysis (preferential fat oxidation over muscle catabolism), increases thermogenesis via brown and beige adipose tissue, and drives hepatic fatty acid oxidation. The net result is meaningfully higher energy expenditure compared to dual agonists, which is the likely explanation for why retatrutide's weight loss numbers are higher than tirzepatide's at comparable timepoints. At 48 weeks in Phase 2, retatrutide at 12 mg produced 24.2% mean weight loss. Tirzepatide's comparable figure from SURMOUNT-1 was 20.9% at 72 weeks.

​

The concern that comes with glucagon receptor agonism is also worth stating directly: glucagon is catabolic. It promotes hepatic glucose output and can lower circulating amino acids, which could reduce muscle protein synthesis. So there was a real question going into the body composition substudy about whether the glucagon component would worsen the lean mass ratio relative to other drugs.

​

What the Phase 2 body composition data actually showed

​

A substudy of the Phase 2 T2D trial, published in The Lancet Diabetes and Endocrinology in June 2025, used DEXA scanning to measure fat mass and lean mass changes separately across retatrutide doses. The key finding: the fat loss index (fat mass loss as a proportion of total weight loss) was 64.6% in a pooled analysis of the 4, 8, and 12 mg arms. That means lean mass comprised roughly 35.4% of total weight lost, a proportion the authors describe as consistent with other obesity treatments.

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For comparison, tirzepatide's DEXA data from SURMOUNT showed fat mass decreasing 33.9% while lean mass decreased 10.9%.

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The short version: despite the theoretical concern that glucagon agonism would worsen the lean to fat loss ratio, Phase 2 data suggests it didn't. The glucagon component appears to preferentially drive fat oxidation rather than muscle catabolism, which is what the preclinical models predicted.

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https://www.sciencedirect.com/science/article/abs/pii/S2213858725000920

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What's still unknown

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The Phase 2 substudy was conducted in people with type 2 diabetes over 36 weeks. TRIUMPH-1 enrolled a broader obesity population over 80 weeks, with a subgroup extending to 104 weeks.

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Full body composition data from TRIUMPH-1 has not been published. The questions that remain:

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Does the favorable lean mass ratio hold at greater weight loss magnitudes? At 28% body weight reduction, the absolute lean mass lost is substantially larger than at 17%, even if the proportion is similar. For older patients or anyone with lower baseline lean mass, that absolute number matters independently of the ratio.

​

Bone mineral density. Significant weight loss of any kind can reduce bone density, and retatrutide has published no bone data yet. This is flagged as a secondary outcome in Phase 3 but results aren't available.

​

Head to head comparison. Every comparison between retatrutide and tirzepatide body composition data right now is cross-trial, meaning different populations, different durations, different study designs. A direct randomized comparison doesn't exist yet.

​

The GI side effect picture

​

Retatrutide's Phase 2 GI side effect rates were higher than tirzepatide's, almost certainly due to the glucagon component. Nausea, vomiting, and diarrhea occurred more frequently, particularly during dose escalation. Whether the titration schedule in Phase 3 mitigates this relative to Phase 2 is something the TRIUMPH data will clarify when it's fully published.

​

What to watch for

​

Full body composition secondary outcomes from TRIUMPH-1 are the most important near-term data point for anyone trying to evaluate retatrutide seriously. The headline weight loss numbers are out. The composition of that weight loss, particularly at the 80 and 104 week timepoints, will either confirm or complicate the Phase 2 picture. Bone mineral density data and outcomes in older adults will matter too, especially as the drug eventually gets used outside the clinical trial population.

​

More stories at r/PeptideTides

This isn't a "which drug wins" post. It's a breakdown of what the third receptor target does mechanistically, what the body composition data actually shows, and what questions are still open going into Phase 3.

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The mechanism difference

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Tirzepatide hits GLP-1 and GIP receptors. Retatrutide adds the glucagon receptor. That third target is the entire basis for the excitement around retatrutide, and it's worth understanding what glucagon receptor agonism actually does rather than treating it as a vague "more is better" addition.

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Glucagon receptor activation drives several distinct effects: it promotes lipolysis (preferential fat oxidation over muscle catabolism), increases thermogenesis via brown and beige adipose tissue, and drives hepatic fatty acid oxidation. The net result is meaningfully higher energy expenditure compared to dual agonists, which is the likely explanation for why retatrutide's weight loss numbers are higher than tirzepatide's at comparable timepoints. At 48 weeks in Phase 2, retatrutide at 12 mg produced 24.2% mean weight loss. Tirzepatide's comparable figure from SURMOUNT-1 was 20.9% at 72 weeks.

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The concern that comes with glucagon receptor agonism is also worth stating directly: glucagon is catabolic. It promotes hepatic glucose output and can lower circulating amino acids, which could reduce muscle protein synthesis. So there was a real question going into the body composition substudy about whether the glucagon component would worsen the lean mass ratio relative to other drugs.

​

​

What the Phase 2 body composition data actually showed

​

​

A substudy of the Phase 2 T2D trial, published in The Lancet Diabetes and Endocrinology in June 2025, used DEXA scanning to measure fat mass and lean mass changes separately across retatrutide doses. The key finding: the fat loss index (fat mass loss as a proportion of total weight loss) was 64.6% in a pooled analysis of the 4, 8, and 12 mg arms. That means lean mass comprised roughly 35.4% of total weight lost, a proportion the authors describe as consistent with other obesity treatments.

​

​

For comparison, tirzepatide's DEXA data from SURMOUNT showed fat mass decreasing 33.9% while lean mass decreased 10.9%.

​

​

The short version: despite the theoretical concern that glucagon agonism would worsen the lean to fat loss ratio, Phase 2 data suggests it didn't. The glucagon component appears to preferentially drive fat oxidation rather than muscle catabolism, which is what the preclinical models predicted.

​

​

https://www.sciencedirect.com/science/article/abs/pii/S2213858725000920

​

​

What's still unknown

​

​

The Phase 2 substudy was conducted in people with type 2 diabetes over 36 weeks. TRIUMPH-1 enrolled a broader obesity population over 80 weeks, with a subgroup extending to 104 weeks.

​

​

Full body composition data from TRIUMPH-1 has not been published. The questions that remain:

​

​

Does the favorable lean mass ratio hold at greater weight loss magnitudes? At 28% body weight reduction, the absolute lean mass lost is substantially larger than at 17%, even if the proportion is similar. For older patients or anyone with lower baseline lean mass, that absolute number matters independently of the ratio.

​

​

Bone mineral density. Significant weight loss of any kind can reduce bone density, and retatrutide has published no bone data yet. This is flagged as a secondary outcome in Phase 3 but results aren't available.

​

​

Head to head comparison. Every comparison between retatrutide and tirzepatide body composition data right now is cross-trial, meaning different populations, different durations, different study designs. A direct randomized comparison doesn't exist yet.

​

​

The GI side effect picture

​

​

Retatrutide's Phase 2 GI side effect rates were higher than tirzepatide's, almost certainly due to the glucagon component. Nausea, vomiting, and diarrhea occurred more frequently, particularly during dose escalation. Whether the titration schedule in Phase 3 mitigates this relative to Phase 2 is something the TRIUMPH data will clarify when it's fully published.

​

​

What to watch for

​

​

Full body composition secondary outcomes from TRIUMPH-1 are the most important near-term data point for anyone trying to evaluate retatrutide seriously. The headline weight loss numbers are out. The composition of that weight loss, particularly at the 80 and 104 week timepoints, will either confirm or complicate the Phase 2 picture. Bone mineral density data and outcomes in older adults will matter too, especially as the drug eventually gets used outside the clinical trial population.

​

​

More stories at r/PeptideTides

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