Retatrutide vs semaglutide vs tirzepatide

This comparison reflects our own reading of the direct trial data as they stand in 2026. We assess these three incretin peptides — retatrutide, semaglutide and tirzepatide — on the basis of their receptor coverage and of their published results, and we flag it clearly whenever a result comes from a study at an earlier phase of development.

The verdict: which peptide comes out on top?

For the maximum weight-loss and liver-fat variables, retatrutide leads the field, with a 24.2% mean loss of body weight in phase 2 and 25.0% at 80 weeks in the phase 3 TRIUMPH-1 trial (2026), driven by its unique triple agonism at the GLP-1/GIP/glucagon receptors. For work on cardiovascular variables, semaglutide wins out, with the deepest evidence base of the three (the SELECT trial); for the most mature phase 3 data set, tirzepatide is the established and consolidated option. The decisive differentiating feature is the number of receptors involved: retatrutide's third receptor (glucagon) raises the efficacy ceiling but demands a slower titration in return, whereas semaglutide and tirzepatide trade a lower ceiling for authorisation as medicinal products and for considerably deeper safety data.

Retatrutide vs. semaglutide vs. tirzepatide: the essentials

• Retatrutide is a triple receptor agonist (GLP-1/GIP/glucagon) that in phase 2 trials shows a 24.2% mean loss of body weight at 48 weeks, as against roughly 22.5% with tirzepatide and roughly 15% with semaglutide
• Only semaglutide (Wegovy) and tirzepatide (Mounjaro) are authorised in the EU; retatrutide is still an investigational drug: Lilly's phase 3 TRIUMPH programme published its first results in 2026, with no marketing authorisation
• Retatrutide's glucagon arm drives hepatic fat oxidation, which explains the reported reductions in liver fat of up to 86%, but it demands a slower titration than either the dual or the single agonists do
• Semaglutide has the deepest cardiovascular evidence base (the SELECT trial); tirzepatide offers mature phase 3 data; retatrutide offers the highest weight-loss ceiling of the three, confirmed at phase 3 by TRIUMPH-1 (2026), but with no cardiovascular outcome data and no authorisation
• The choice of compound depends on the research variable in question: the weight-loss ceiling points towards retatrutide; cardiovascular variables point towards semaglutide; the largest phase 3 evidence base points towards tirzepatide

Last updated: 2026

How the three peptides differ from one another

Semaglutide is a single agonist of GLP-1 and nothing more. Tirzepatide is a dual GLP-1/GIP agonist. Retatrutide is a triple GLP-1/GIP/glucagon agonist, a structure that retatrutide alone possesses among the three [1].

The maximum weight loss seen in the trials scales with the number of receptors. Retatrutide reached a mean reduction in body weight of 24.2% in the phase 2 trial published by Jastreboff et al. (NEJM, 2023), at a dose of 12 mg and at 48 weeks [1]. Tirzepatide reached around 22.5% in SURMOUNT-1, at a dose of 15 mg and at 72 weeks [4]. Semaglutide reached around 14.9% in STEP 1, at a dose of 2.4 mg and at 68 weeks [5].

For those doing research in Spain, the breadth of receptor coverage predicts both the efficacy and the complexity of the titration. Retatrutide's glucagon arm adds a hepatic fat-oxidation pathway that the other two compounds lack altogether, which is why its titration protocol calls for slower up-titration steps than semaglutide dosing does, in order to manage the glycaemic effects that are linked to glucagon.

Summary table

Receptor mechanisms: GLP-1, GIP and glucagon explained

Each one of the incretin receptors contributes a metabolic effect of its own. Semaglutide binds to the GLP-1 receptor only. Tirzepatide binds to both GLP-1 and GIP. Retatrutide binds to all three of them, and that third receptor, the glucagon receptor, uncouples weight loss from the suppression of appetite and channels it instead through energy expenditure in the liver [1].

GLP-1 receptor agonism

Activation of the GLP-1 receptor suppresses appetite by slowing down gastric emptying, by reinforcing central satiety signalling in the hypothalamus and by triggering glucose-dependent insulin secretion from the beta cells of the pancreas [1]. That is the entire pharmacological surface that semaglutide has at its disposal. It explains both its maximum weight loss of around 14.9% in STEP 1 and its dose-limiting nausea profile at the same time: the delay in gastric emptying is the very same pathway that drives the adverse effects seen in the upper gastrointestinal tract. If you are titrating upwards from 0.25 mg, lean on the semaglutide dosing schedule in order to manage that trade-off.

GIP receptor agonism

Activation of the GIP receptor reinforces glucose-dependent insulin secretion and it appears to blunt the nausea ceiling that is seen with pure GLP-1 agonism on its own. That is the reason why tirzepatide tolerates higher functional doses than semaglutide does for the same weight-loss variables [3]. GIP also modulates lipid metabolism in the adipocytes and improves the clearance of lipids after meals. Tirzepatide's combined GLP-1/GIP signal is the mechanistic basis for its result of around 22.5% in SURMOUNT-1, which beats semaglutide's STEP 1 figure by something like 7.6 percentage points.

Glucagon receptor agonism: the differentiating feature

Activation of the glucagon receptor increases both hepatic fat oxidation and resting energy expenditure. It is the mechanism that the guides on dual agonists routinely leave out when they set out to explain the efficacy advantage that retatrutide has [1]. Historically, glucagon agonism was deliberately avoided in the design of drugs for obesity, because glucagon without any counter-regulation increases hepatic glucose release and runs the risk of hyperglycaemia.

Retatrutide mitigates this by means of a balanced triple agonism. The simultaneous GLP-1 and GIP arms drive a glucose-dependent insulin secretion that offsets the gluconeogenesis that glucagon induces, which produces net euglycaemia alongside increased lipolysis (Jastreboff et al., NEJM, 2023) [1]. The phase 2a MASLD sub-study (Sanyal et al., Nat Med 2024) attributes to that glucagon arm a relative reduction in liver fat of up to 86% with 12 mg at 48 weeks [9].

The practical consequence of this is that a slower up-titration is required than is the case in the regimens with single or dual agonists. The retatrutide titration protocol reflects this by lengthening the intervals between dose increases so that the glycaemic counter-regulation has the time it needs to stabilise.

Weight-loss data compared: trial results side by side

Across the three trials that are relevant to authorisation, the maximum mean reductions in body weight rank as follows: retatrutide 12 mg with 24.2% (48 weeks, phase 2), tirzepatide 15 mg with 22.5% (72 weeks, phase 3) and semaglutide 2.4 mg with 14.9% (68 weeks, phase 3) [1][4][5]. Retatrutide's figure is the highest that has been reported so far and comes from a shorter phase 2 trial; in 2026 the phase 3 TRIUMPH-1 trial (2,339 adults, 80 weeks) confirmed it with 25.0% at 12 mg against 3.9% with placebo [11].

Why these figures are not directly comparable

Comparing across trials overstates the degree of precision that is available. STEP 1, SURMOUNT-1 and the phase 2 trial by Jastreboff each enrolled different populations from one another. The BMI thresholds, the presence of type 2 diabetes and the ethnic composition all varied from one to the next. The durations of the studies were different as well. The reporting of the results as placebo-adjusted change or as total change was inconsistent across the secondary summaries. Retatrutide's 48-week curve had not yet reached a plateau at the time of the analysis, so the 24.2% figure probably underestimates the steady state at 72 weeks, which would be the equivalent of the SURMOUNT-1 window [1].

The study population weighs more heavily than most comparison tables are willing to admit. SURMOUNT-1 excluded people with type 2 diabetes. The parallel SURMOUNT-2 cohort, with type 2 diabetes, lost around 6-7 percentage points less at the very same dose. That pattern repeated itself with retatrutide at phase 3: in TRIUMPH-2, the type 2 diabetes cohort lost 18.8% at 80 weeks with 12 mg (against 5.1% with placebo), compared with 25.0% in TRIUMPH-1 without diabetes [11][12].

The maturity of the evidence is the real differentiator

Semaglutide has the deepest evidence base of the three. It is backed by the complete STEP 1-8 programme, by the SUSTAIN cardiovascular data and by several years of prescribing experience in routine care within specialist weight-management programmes. The practical experience that has been gained with dose escalation is well captured in the semaglutide dosing guide.

Tirzepatide has completed the phase 3 SURMOUNT programme in full and is in routine clinical use under the name Mounjaro. The details of the SmPC for weight management should be checked against the primary source before relying on them.

Retatrutide remains an investigational drug. Lilly's phase 3 TRIUMPH programme published its first results in 2026: TRIUMPH-1 (NCT05929066, completed) in 2,339 adults with obesity without diabetes, with 17.6%, 23.7% and 25.0% mean weight loss at 80 weeks with 4, 9 and 12 mg against 3.9% with placebo [8][11]; TRIUMPH-2 in 1,152 adults with obesity and type 2 diabetes, with 11.9%, 16.8% and 18.8% against 5.1% with placebo [12]; and the obstructive sleep apnoea sub-studies, with reductions in the apnoea-hypopnoea index of up to 34.3 events per hour at 80 weeks [13]. The most frequent adverse events were gastrointestinal: in TRIUMPH-2, diarrhoea affected 34% and nausea 28% at 12 mg (13% and 8% with placebo), and discontinuations for adverse events ran at 8-12% with 9-12 mg against 5% with placebo [12]. Those results confirm the phase 2 signal, but they are not equivalent to an authorisation: any purchasing decision based on them should take into account the slower titration described in the retatrutide titration protocol.

The glucagon advantage: why retatrutide's ceiling is higher

Retatrutide's higher weight-loss ceiling exists because glucagon receptor agonism adds a second, parallel fat-loss pathway that tirzepatide and semaglutide do not touch at all. GLP-1 and GIP reduce energy intake by suppressing the appetite and by slowing down gastric emptying. The glucagon arm, by contrast, increases energy expenditure by accelerating the oxidation of fatty acids in the liver. These are not redundant mechanisms by any means: they act on different tissues and they work on different timescales.

The mechanistic chain is a concrete one. Activation of the hepatic glucagon receptor upregulates carnitine palmitoyltransferase 1 (CPT1), which is the rate-limiting enzyme that transports long-chain fatty acids across the outer mitochondrial membrane so that they can undergo β-oxidation. With more CPT1 capacity available to it, the liver oxidises a larger share of the incoming free fatty acids instead of re-esterifying them back into triglycerides. Two clinical signatures follow on from this: a measurable increase in resting energy expenditure (REE) that is independent of the caloric deficit, and sizeable reductions in the amount of intrahepatic lipid.

The phase 2a MASLD sub-study described relative reductions in liver fat of up to 86% with retatrutide 12 mg at 48 weeks, attributed mechanistically to the glucagon component [9]. Direct human CPT1 biomarker data from a 2023-to-2026 cohort also remain unverified within this data set. The CPT1 mechanism is inferred from preclinical work and from the foundational REE data on the GLP-1/GIP/glucagon triagonist published by Finan et al. (Nat Med, 2015), which remain the mechanistic anchor for any triple-agonist programme that has come since [10].

The clinical expression of this appears in Jastreboff et al. (NEJM 2023), where retatrutide 12 mg produced a 24.2% mean loss of body weight at 48 weeks without ever reaching a plateau [1]. Tirzepatide's SURMOUNT-1 curve flattened out earlier and at a lower ceiling, which is consistent with a mechanism that mainly limits intake rather than one that also raises expenditure.

The price of all this is the risk of hyperglycaemia. Glucagon agonism taken on its own increases hepatic glucose release. In retatrutide, the insulinotropic effect of the GLP-1 arm offsets it, but it does so only if the glucagon component is introduced gradually relative to the exposure to GLP-1/GIP. That is why retatrutide's titration is slower and more finely stepped than tirzepatide's, and it is also why missing doses has a different set of consequences. The retatrutide titration protocol deals with the specific intervals between steps. The contrast with semaglutide's simpler escalation is documented in the semaglutide dosing guide.

Adverse-effect profiles: what the trials described

Nausea is the dominant adverse event with all three of the compounds, but its frequency and its severity track the speed of the titration far more closely than they track the number of receptors that are involved. Pooling all of the doses together, Jastreboff et al. (NEJM 2023) described nausea in around 47% of the participants on retatrutide. STEP 1 (NEJM 2021) described around 44% with semaglutide 2.4 mg. SURMOUNT-1 (NEJM 2022) described around 31% with tirzepatide 15 mg [1][4][5]. Those figures are not directly comparable with one another: the titration schedules, the dose ceilings and the study populations were all different from trial to trial. Only comparisons that are made within a single trial should be regarded as causal.

One striking detail stands out: adding GIP agonism (tirzepatide) appears to blunt, rather than to worsen, the nausea that is linked to GLP-1, which is in line with the lower SURMOUNT-1 figure. Adding glucagon agonism (retatrutide) does not reproduce that protective effect. The phase 2 data show that the gastrointestinal events cluster within the dose-escalation windows and not once the steady state has been reached [1].

Adverse events reported in the trials

Vomiting and diarrhoea followed the very same order in each one of the trials. Discontinuations for gastrointestinal reasons stayed down in single figures across all three of the programmes [1][4][5]. Direct head-to-head nausea data from SURPASS-CVOT, or from an equivalent comparison from 2024 to 2026, are not available in the sources analysed here.

The glucagon arm adds a consideration of its own: in non-diabetic research subjects, the insulinotropic effect of GLP-1 usually offsets the hepatic glucose release that is linked to glucagon, but a rapid escalation can nonetheless produce a transient dysglycaemia. That is the practical reason why the retatrutide titration protocol uses smaller step intervals than semaglutide's simpler escalation does.

Note for researchers: in the retatrutide phase 2 data, the frequency of nausea reached its peak during the titration phase and fell away again at the steady-state dose. A structured titration protocol is the single modifiable variable with the greatest bearing on tolerability.

Authorisation status in Spain (2026)

Semaglutide and tirzepatide are both authorised medicinal products in the EU. Retatrutide is not one: although the first phase 3 results were published in 2026 [11], it remains available exclusively as a research compound for as long as no marketing authorisation exists. The three peptides sit on different regulatory planes from one another, and conflating them is the single most frequent error in comparisons that are aimed at buyers.

Semaglutide (Ozempic, Wegovy)

Ozempic is authorised for the treatment of type 2 diabetes. Wegovy is authorised for chronic weight management. Both of them are medicinal products that are subject to medical prescription.

Tirzepatide (Mounjaro, Zepbound)

Mounjaro is authorised for the treatment of type 2 diabetes and it is a medicine that is subject to medical prescription. The weight-management indication (marketed in the United States under the name Zepbound) is described as being available in the secondary summaries from 2026 [7]. The exact scope of the SmPC has not been confirmed from a primary regulatory source. Treat the formal authorisation status for weight management as unverified until there is direct confirmation of it.

Retatrutide

In 2026 retatrutide has no authorisation from the EMA. Lilly's phase 3 TRIUMPH programme published its first results in 2026 (TRIUMPH-1 and TRIUMPH-2) [8][11][12], which does not amount to an authorisation. Secondary commentary from 2026 estimates a possible authorisation towards the end of 2027 or at some point in 2028. In Spain it is supplied exclusively for laboratory and analytical purposes and for nothing else. Any retatrutide titration protocol that is cited in research contexts is not a clinical dosing schedule and should not be read as one.

Notice: Body Pharm products, including the retatrutide and tirzepatide reference materials, are sold exclusively for research and analytical purposes. They are not medicinal products, they are not intended for human consumption and they are no substitute for an authorised prescription-only medicine that has been obtained with a prescription.

Retatrutide vs. tirzepatide: head to head for researchers

If you are choosing between the two most potent compounds in this class, retatrutide currently shows an advantage of 1.5 to 2 percentage points in weight loss over tirzepatide when measured at a comparable duration, but tirzepatide has considerably more phase 3 evidence behind it and a confirmed authorisation as a medicinal product [1][4].

Receptor overlap

Both of the compounds are GIP/GLP-1 co-agonists. Retatrutide adds glucagon receptor agonism on top of that, which drives hepatic fat oxidation and resting energy expenditure rather than the suppression of appetite alone [1]. The 86% relative liver-fat reduction figure reported in the phase 2a MASLD sub-study is attributed directly to that very glucagon arm [9]. Tirzepatide's mechanism stays entirely within the incretin pathways, which is the reason why its weight-loss ceiling falls below retatrutide's in the head-to-head modelling.

Difference in weight loss

Retatrutide 12 mg produced a 24.2% mean loss of body weight at 48 weeks in the phase 2 trial in obesity (Jastreboff et al., NEJM 2023) [1]. Tirzepatide's SURMOUNT programme finishes lower down when measured at a comparable duration [4]. The historical caveat was that retatrutide's figure came from a phase 2 trial (a smaller n, with larger selection effects), whereas tirzepatide's data had reached phase 3 maturity; in 2026 the phase 3 TRIUMPH-1 trial recorded 25.0% at 80 weeks with 12 mg, against 22.5% in SURMOUNT-1 at 72 weeks, so the margin held at phase 3 [4][11].

Presentation and titration

Body Pharm offers retatrutide in 32 mg and 64 mg multi-dose pens, and tirzepatide in a 60 mg pen. All of them set the dose directly in milligrams on the dial. Both compounds are reference materials that are exclusively for laboratory use. The complexity of the titration differs a great deal between the two of them. Tirzepatide follows a predictable monthly step of 2.5 mg. Retatrutide climbs in three four-week steps — 2 mg, 4 mg and 8 mg per week — with a maximum dose of 12 mg per week, and the glucagon arm, which causes a dose-dependent rise in heart rate and shifts in hepatic glucose release, is the reason why the retatrutide titration protocol holds each step for the full four weeks (see also the semaglutide dosing guide for the purely incretin titration benchmarks).

Decision framework

Choose tirzepatide if what you need is mature phase 3 safety data, a confirmed authorisation pathway, a simpler titration or a comparator that has established signals on cardiovascular variables. Choose retatrutide if the research question points specifically towards hepatic steatosis, fat oxidation or the contribution that the glucagon axis makes to energy expenditure, and if you are able to accept a thinner phase 3 evidence base and a longer titration window.

Retatrutide vs. semaglutide: is the triple agonist worth it?

For pure weight-loss variables, retatrutide beats semaglutide at the maximum dose by around 9 percentage points: 24.2% as against roughly 15% mean loss of body weight over a comparable duration [1][5]. In the context of cardiovascular research, however, semaglutide remains by a very wide margin the better-documented compound of the two.

The difference in mechanism explains the difference in fat loss. Semaglutide is a single GLP-1 agonist. Retatrutide adds activity at both the GIP and the glucagon receptors, and the glucagon arm drives the hepatic fat oxidation and the energy-expenditure component that the single agonists are structurally unable to replicate [1]. The phase 2a MASLD sub-study described relative reductions in liver fat of up to 86% with retatrutide 12 mg at 48 weeks, attributed mechanistically to activity at the glucagon receptor [9].

Semaglutide's counter-strengths lie in the evidence, not in the pharmacology. The SELECT trial (NEJM 2023) showed that semaglutide 2.4 mg reduced major cardiovascular events by around 20% as against placebo in non-diabetic adults who had obesity and established cardiovascular disease [2]. As of 2026, retatrutide has no data from any cardiovascular outcomes trial; the published phase 3 trials (TRIUMPH-1 and TRIUMPH-2) measured weight, glycaemic control, knee pain and sleep apnoea, not cardiovascular events [11][12][13]. Semaglutide also carries around five additional years of real-world post-marketing pharmacovigilance behind it in routine practice.

Research note

Semaglutide is the reference compound against which the newer active substances are measured. Anyone who moves straight to a triple agonist without first characterising the response to semaglutide in their own model is effectively skipping the control arm. The semaglutide dosing protocol is the baseline titration curve that we would establish before introducing the glucagon-axis variables covered in the retatrutide titration protocol.

The honest answer is this: if the research question concerns the weight-loss ceiling or liver fat, then retatrutide justifies the switch. If it concerns the modification of cardiovascular risk or long-term safety, then semaglutide still wins on the depth of its data, not on potency.

How to choose: a decision framework for research in 2026

The choice of compound depends entirely on which trial variable your research question corresponds to. The matrix below maps the five most frequent research objectives of 2026 to the compound whose published phase 2/3 data answer them in the most direct way, anchored in SURMOUNT-1 (tirzepatide), in STEP 1 (semaglutide) and in Jastreboff et al. NEJM 2023 (retatrutide).

Retatrutide and tirzepatide are both available through Body Pharm exclusively for research purposes. The titration curves weigh more heavily on tolerability than the choice of compound itself ever does. The semaglutide dosing guide and the retatrutide titration protocol cover the dose-escalation schedules that are referred to in the source studies.

Methodological note

We built this matrix by mapping each row to the specific trial variable that, as of mid-2026, provided the primary evidence of the highest quality: percentage change in body weight for efficacy (Jastreboff 2023, SURMOUNT-1, STEP 1), three-point MACE for the cardiovascular variables (SELECT), MRI-PDFF for liver fat (the retatrutide phase 2a MASLD sub-study [9]) and rates of treatment-emergent adverse events for the gastrointestinal burden. Where head-to-head data from 2024 to 2026 are missing, in particular for the frequency of nausea with tirzepatide as against semaglutide, the recommendation is flagged as unverified rather than being inferred across studies with different populations and different titration schedules.

Buying retatrutide in Spain: availability in 2026

In 2026, Body Pharm offers two presentations of retatrutide: the Retatrutide 32 mg multi-dose pen and the Retatrutide 64 mg multi-dose pen, both of them shipped within Spain exclusively for research and analytical purposes. Tirzepatide 60 mg can currently be reserved by way of the waitlist, and it is not available for immediate dispatch from stock at present.

Semaglutide appears in this comparison solely as a reference compound. Body Pharm does not supply it in Spain, so nothing that is said about it here describes a product that is in this catalogue.

Both of the retatrutide pens are pre-filled multi-dose devices for subcutaneous injection, each with a 3 ml cartridge, and they set the dose directly in milligrams. The dosing protocol is exactly the same for the two of them: 2 mg per week for 4 weeks, then 4 mg per week for 4 weeks and then 8 mg per week for 4 weeks, with a maximum dose of 12 mg per week. Both of the pens can set every one of those doses; the only difference between them is the total peptide content, so the 64 mg pen lasts longer before it runs out.

That is the product protocol, and it should not be confused with the ladders used in the published trials, which are a different matter altogether: the phase 3 TRIUMPH programme escalated 2 → 4 → 6 → 9 → 12 mg weekly, and the 12 mg arm of the phase 2 trial is where the 24.2% reduction in body weight at 48 weeks was recorded in NEJM 2023 [1][8]. Those figures are cited here purely as trial data, and not as a dosing schedule for these particular pens.

The retatrutide titration protocol walks through the dose-escalation schedule one step at a time. The semaglutide dosing guide covers the comparator compound in turn.

Ordering and shipping

Shipping is within Spain only; standard delivery usually takes 3-5 working days. No prescription is required, because these compounds are sold exclusively for in vitro and analytical research. They are not authorised for administration to people, and retatrutide remains an investigational drug for as long as no marketing authorisation exists, although the first phase 3 results were published in 2026 [8][11]. The person who buys is responsible for ensuring that the handling is exclusively for research purposes. The products are not intended for personal therapeutic use, for sporting purposes or for resale into the consumer supply chain in any form.

Frequently Asked Questions

Is retatrutide more potent than tirzepatide?

Retatrutide produced a greater mean weight loss than tirzepatide did in their respective trials in obesity. Jastreboff et al. (NEJM 2023) described a 24.2% reduction in body weight at 48 weeks with retatrutide 12 mg [1]. SURMOUNT-1 described around 22.5% at 72 weeks with tirzepatide 15 mg [4]. There are no head-to-head data available as yet.

Which receptors does retatrutide act on?

Retatrutide is a triple agonist that acts simultaneously on the GIP, the GLP-1 and the glucagon receptors [1]. The glucagon arm sets it apart from tirzepatide (dual GIP/GLP-1) and from semaglutide (GLP-1 only), and it is the mechanistic basis for the hepatic fat-oxidation signal, including the 86% reduction in liver fat that is described in the phase 2a MASLD sub-study [9].

Is retatrutide authorised in Spain?

No. In 2026 retatrutide is still an investigational drug and it has no authorisation as a medicinal product of any kind. The first phase 3 results from Lilly's TRIUMPH programme (TRIUMPH-1 and TRIUMPH-2) were published in 2026 [8][11][12], and a secondary estimate from 2026 places a possible authorisation at the end of 2027 or at some point in 2028. Its supply in Spain is limited to in vitro and analytical research, and not to human use.

Can I buy retatrutide in Spain?

Yes, but exclusively for research purposes. Suppliers ship retatrutide as a research chemical for in vitro and analytical work. No prescription is envisaged at all, because the compound is not authorised for use in humans [8]. The multi-dose pen formats (32 mg, 64 mg) correspond to the titration schedule that was used in the phase 2 trial by Jastreboff. You will find the details of the dose escalation in the retatrutide titration protocol.

What is the difference between a dual agonist and a triple agonist?

A dual agonist activates two of the incretin receptors (tirzepatide: GIP + GLP-1). A triple agonist activates three of them (retatrutide: GIP + GLP-1 + glucagon) [1]. The additional activity at the glucagon receptor drives hepatic fat oxidation and a greater energy expenditure, which is something that the dual agonists do not stimulate directly [10].

How does semaglutide compare with tirzepatide for weight loss?

Tirzepatide outperformed semaglutide in the SURMOUNT-1 trial. Semaglutide (a single GLP-1 agonist) typically produces a loss of around 14.9% at 68 weeks, as seen in STEP 1, as against around 22.5% with tirzepatide 15 mg in SURMOUNT-1 [4][5]. You will find dosing guidance in the semaglutide dosing guide.

Next steps

Your research variable is what determines which compound to prioritise. If your question centres on efficacy in weight loss or on the reduction of liver fat, lean on the retatrutide titration protocol and order either a 32 mg or a 64 mg pen from Body Pharm. If you need mature phase 3 safety data or cardiovascular variables, the semaglutide literature is the place to start, and the semaglutide dosing guide summarises what has been published on that compound; Body Pharm does not supply it. If what you need is a balance between efficacy and phase 3 evidence, tirzepatide is the established option. Contact Body Pharm directly in order to confirm the current stock and the delivery times for whichever compound you have chosen.

Sources

1. Jastreboff AM, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023. pubmed.ncbi.nlm.nih.gov/37366315
2. Lincoff AM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). N Engl J Med. 2023. pubmed.ncbi.nlm.nih.gov/37952131
3. Frías JP, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2). N Engl J Med. 2021. pubmed.ncbi.nlm.nih.gov/34170647
4. Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022. pubmed.ncbi.nlm.nih.gov/35658024
5. Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021. pubmed.ncbi.nlm.nih.gov/33567185
6. EMA, EPAR and Summary of Product Characteristics (SmPC) for Wegovy (semaglutide 2.4 mg): EU authorisation for weight management. ema.europa.eu
7. EMA, EPAR and Summary of Product Characteristics (SmPC) for Mounjaro (tirzepatide): EU authorisation and indications. ema.europa.eu
8. ClinicalTrials.gov, retatrutide trial registry (phase 3 TRIUMPH programme), accessed October 2026. clinicaltrials.gov
9. Sanyal AJ, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024;30:2037-2048. pubmed.ncbi.nlm.nih.gov/38858523
10. Finan B, et al. A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents. Nat Med. 2015;21:27-36. pubmed.ncbi.nlm.nih.gov/25485909
11. Jastreboff AM, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity (TRIUMPH-1). N Engl J Med. 2026. pubmed.ncbi.nlm.nih.gov/42814954
12. Bellido V, et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. Lancet. 2026;408:1455-1472. pubmed.ncbi.nlm.nih.gov/42810372
13. Grunstein RR, et al. Retatrutide Once Weekly for Treatment of Obstructive Sleep Apnea (TRIUMPH-1-OSA / TRIUMPH-2-OSA). N Engl J Med. 2026. pubmed.ncbi.nlm.nih.gov/42904878