Macupatide (LY3532226)_Dosage, benefits & legal status
Also known as LY3532226, LY-3532226
The experiment that isolates what GIP does.
Common vial size is what vendors typically sell, not a recommendation. Enter your own vial in the calculator.
What is Macupatide (LY3532226)?
Plain language first. The technical label stays, but it never stands alone.Overview
Tirzepatide hits two receptors, GIP and GLP-1, and the usual description of the GIP part as a helper that boosts what GLP-1 does has never been well pinned down. Macupatide is the drug that lets you check, because it is a GIP agonist studied on its own. The published answer is more interesting than the usual framing: GIP agonism mainly made the body more sensitive to its own insulin rather than making it secrete more. Note also what the side effects were. The common problems were injection-site reactions and diarrhea, not the nausea and vomiting people associate with this class.
Macupatide is a long-acting acylated agonist at the GIP receptor. A phase 1b randomized controlled trial published in June 2026 studied it alone and with dulaglutide in people with type 2 diabetes on metformin, using hyperinsulinemic euglycemic clamps at baseline and 12 weeks. Its published conclusion is that chronic GIP receptor activation in people with type 2 diabetes leads primarily to increased insulin sensitivity, with a smaller effect on secretion, and that combining GIP with GLP-1 agonism improves both more than GLP-1 alone. Two phase 2 programs are running, one of 200 participants with type 2 diabetes and a phase 2b of 400 without, the latter in combination with the amylin agonist eloralintide. There is no phase 3 and no monotherapy obesity program.
What it's used for
Nothing. It has no approval anywhere and is in phase 2 development for type 2 diabetes and obesity, including in combination with an amylin agonist.
How does Macupatide (LY3532226) work?
What it does in the body, and where.This compound is useful less as a future drug than as an experiment. It answers a question tirzepatide raised and could not settle.
- 01The puzzle tirzepatide left behindTirzepatide activates both the GLP-1 and GIP receptors and outperforms GLP-1-only drugs. The natural assumption is that the GIP component adds to insulin secretion. The trouble is that a dual agonist cannot tell you which receptor did what, and a review in a major diabetes journal states plainly that the relative contribution of the two receptors to tirzepatide's effects is not yet established.
- 02The paradox that makes it harderBoth GIP agonists and GIP antagonists have been pursued for weight, and that sounds self-contradictory. The best published reconciliation is that chronic stimulation of the GIP receptor on fat cells desensitizes it, so sustained agonism ends up mimicking functional blockade. If that is right, then agonist and antagonist approaches can converge on a similar endpoint by opposite routes, and arguing from the label on the bottle is not enough.
- 03What the clean experiment foundThe phase 1b trial gave macupatide alone, dulaglutide alone, or both, to people with type 2 diabetes on metformin, and measured insulin sensitivity and secretion directly with clamps. Its published conclusion is that chronic GIP receptor activation leads primarily to increased insulin sensitivity. Secretion improved as well but less so, and the combination beat either drug alone on all the indices. So the GIP half is not mainly a secretion booster.
- 04The side-effect profile points the same wayThe most common adverse events in that trial were injection-site reactions and diarrhea. Nausea and vomiting, the signature of GLP-1 receptor activation, were not what stood out. That is consistent with GIP agonism working through a different route, and it is also the practical reason a GIP agonist might be combined with something else rather than used alone.
- 05Where it is goingInto combinations. The phase 2b pairs it with eloralintide, an amylin agonist, in people without type 2 diabetes. Lilly describes that program as the combination rather than as macupatide by itself, and it is running at least one other eloralintide combination separately. The likely future of this molecule is as a component, not a standalone product.
What else is it used for?
Each group carries its own evidence level.Approved means regulators have cleared it for that purpose. Investigational means it is in trials. Early research means it is being studied and is not established.
What isolating GIP agonism showed
Early research- Human trialThe published phase 1b conclusion is that chronic GIP receptor activation in type 2 diabetes leads primarily to increased insulin sensitivity, with a smaller effect on insulin secretion.
- Human trialCombining GIP with GLP-1 agonism improved both secretion and sensitivity more than GLP-1 alone.
- Human trialMost common adverse events were injection-site reactions and diarrhea, not nausea and vomiting.
The agonist and antagonist paradox
none- Lab studyBoth GIP agonists and GIP antagonists have been developed for weight. Published work shows chronic agonism desensitizes the GIP receptor on fat cells, mimicking functional blockade, and that is how both directions can be pursued coherently.
- ReviewA major diabetes journal review states the relative contribution of the GIP and GLP-1 receptors to tirzepatide's effects is not yet established.
What is not documented
none- No dataThe frequently repeated claim that macupatide has no GLP-1 or glucagon receptor activity is not documented in any source we opened, and no potency or selectivity figures exist publicly.
- No dataNo phase 3 program and no monotherapy obesity program. The phase 2b pairs it with the amylin agonist eloralintide.
Three things. The published phase 1b trial paired macupatide with dulaglutide, not with eloralintide, and sources describing that paper as an eloralintide combination study have the wrong partner; eloralintide enters later, in the phase 2b. Second, macupatide is routinely described as a pure GIP agonist with no GLP-1 or glucagon activity, and we could not find that selectivity documented anywhere, nor any numbers for it. Calling it a GIP receptor agonist is supported; calling it clean is not. Third, the phase 1b measured insulin sensitivity and secretion under clamp conditions, not weight loss, so quoting it as evidence of weight effect misreads what was done. A fourth point is worth adding for anyone reading about tirzepatide: the idea that the GIP component mainly boosts insulin secretion does not survive this experiment, where the dominant effect was on sensitivity.
The published record
Papers and trials about Macupatide (LY3532226)
Searched: macupatide, LY3532226, LY-3532226.
Left out: GIP (a class term with a large incretin literature, most of it about tirzepatide); GIP receptor agonist (same problem, and it also pulls the GIP antagonist literature); tirzepatide (has its own slug; the point of this card is what it isolates from tirzepatide, not tirzepatide itself); eloralintide (has its own slug; it is a phase 2b combination partner, not the partner in the published phase 1b); dulaglutide (the actual phase 1b comparator, with its own substantial literature).
5 papers tagged human · 1 not reviews or lab · 1 clinical trial publications
4 registered trials · none with posted results
Furthest stage reached: Phase 2, under way
Counted from Europe PMC indexing, not read by a person; a human tag can land on reviews, commentary or lab papers; clinical trial publications is the narrower count.
At a glance
Four things to know about Macupatide (LY3532226)
Evidence
Investigational
Category
Weight loss and metabolic
Common vial
Varies
Half-life
Long-acting, no figure published
How much, and do you cycle it?
The range, and whether you take breaks.No established dose, not established. Not applicable No range
No approved product and no published dose regimen, so no cycling scheme exists.
Long-acting, no figure publishedNo figure
Described as long-acting and acylated, and studied with 12-week dosing, but no numeric human half-life appears in the sources read for this page. No figure is given rather than quoting one we could not source.
You can compare this against the whole library to see where it sits.
How do I dose and price it?
Enter your vial and your dose. Pick a mix. We show the draw and the cost.The vial holds a fixed amount of drug. Adding more water does not make more drug, it just spreads it thinner, so you draw a bigger number on the syringe for the same dose.
Choose your mix
Measuring the water1 mL = one full 100-unit syringe.
How do you store it?
Before mixing, and after.Nothing to store: it is not sold anywhere.
Macupatide (LY3532226) has never been marketed, so there is no vial, pen or bottle to keep at home. Supplies for a trial are made, stored and dispensed by the sponsor and the trial pharmacy under conditions set in the protocol. Anything offered for sale under this name did not come from that supply chain.
What are the side effects and cautions?
Known cautions and warnings for this compound.Who should avoid it
- Any use at all: there is no approved product and no established dose
- Reading its phase 1b results as weight-loss evidence, since the trial measured insulin sensitivity and secretion rather than weight
Stop and get help
- Not applicable. There is no approved product.
Common effects
- Injection-site reactions and diarrhea were the most common adverse events in the published phase 1b trial
Where this page says nothing is established, that means nobody has studied it, not that a compound is safe.
Is Macupatide (LY3532226) approved?
And where the numbers on this page come from.No. Macupatide (LY3532226) is not approved anywhere and is currently in company-run clinical trials. There is no legal route to obtain it outside a trial.
- Approval statusInvestigational
- RouteUnder the skin (subcutaneous)
- Checked30 October 2026
- DoseNo dose has been established in people.
- Vial sizeFrom what vendors typically list; not a recommendation.
- Sources
What has happened recently
Not approved anywhere. Development is at phase 2, and the programs are worth distinguishing. One trial of about 200 participants with type 2 diabetes is listed as active and no longer recruiting. A phase 2b of about 400 participants without type 2 diabetes is recruiting and pairs macupatide with eloralintide, Eli Lilly's amylin agonist, already covered on this site; the company lists that program as the combination rather than as macupatide alone. There is no phase 3. One claim circulating about this molecule should be treated with care: it is widely described as having no GLP-1 or glucagon receptor activity, and we could not find that selectivity documented in any source, nor any potency or selectivity figures. It is accurate to call it a GIP receptor agonist. It is not currently possible to state how clean that selectivity is.
You can compare this against the whole library, or read how to check a seller.
What else is like Macupatide (LY3532226)?
Others in Fat loss without GLP-1, side by side.If you're weighing Macupatide (LY3532226), it's worth reading Nisotirostide (LY3457263), Peptide YY, and PYY1875 (NNC0165-1875) in the same class.
The experiment that isolates what GIP does.
- Dose
- No established dose
- How often
- Not established
A gut-hormone analog that only works as an add-on.
- Dose
- No established dose
- How often
- Not established
A hormone whose effect survives replication in people and keeps failing to become a medicine.
- Dose
- No established dose
- How often
- Not applicable
A long-acting copy of the gut fullness hormone PYY that Novo Nordisk tested on top of semaglutide. It added 2.15 points of weight loss with frequent nausea, and development ended in 2023.
- Dose
- 1.0 mg once weekly, added to semaglutide 2.4 mg (phase 2 trial)
- How often
- Once weekly (phase 2 trial)
Guides for this compound
- How to Reconstitute a Peptide
Mix peptide powder with bacteriostatic water, step by step.
- How to Read an Insulin Syringe
Read the units, convert to millilitres, and draw the exact dose.
- mcg vs mg: The Peptide Dosing Mistake to Avoid
Your vial says mg and your protocol says mcg. Here is the conversion and how to check it.
- How to Read a Peptide COA
What the purity number does and does not tell you, and how to spot an edited report.
- How to Vet a Peptide Vendor
Independent COAs, HPLC purity, and the red flags that mean walk away.
Sources
- Heise and colleagues, Diabetes Obesity and Metabolism, the phase 1b trial(2026)Insulin Sensitivity and Beta Cell Function With Macupatide Alone or With Dulaglutide in Type 2 Diabetes, a phase 1b randomized controlled trial, volume 28, issue 8, pages 7196 to 7206, published online June 2, 2026. Note the partner in this trial is dulaglutide, not eloralintide. Double-blind, in people with type 2 diabetes taking metformin; insulin sensitivity, insulin secretion rate and clamp disposition index measured from hyperinsulinemic euglycemic clamps at baseline and 12 weeks. Macupatide alone significantly increased insulin sensitivity and, to a lesser but still significant extent, insulin secretion; the combination gave numerically larger gains than either alone on all indices. Most common adverse events were injection site reactions and diarrhea, discontinuations uncommon, no deaths. Conclusion verbatim: chronic GIP receptor activation in individuals with T2D leads primarily to increased insulin sensitivity. The abstract does not label which numeric values belong to which arm, so no arm-attributed figures are quoted on this page. DOI resolved at Crossref.
- Killion and colleagues, Nature Communications, chronic GIP receptor agonism(2020)The source for the reconciliation of the GIP agonist and antagonist paradox: chronic agonism at the GIP receptor desensitizes the receptor on adipocytes, so sustained stimulation can mimic functional antagonism. This is why pursuing both directions for weight is not as contradictory as it first appears. DOI resolved at Crossref.
- Trial registry records NCT07215559 and NCT07589608(2026)The two phase 2 programs. NCT07215559 enrolls about 200 participants with type 2 diabetes and is listed as active and not recruiting. NCT07589608 is a phase 2b of about 400 participants without type 2 diabetes, recruiting, in which eloralintide appears in most of the treatment arms, so the combination rather than macupatide alone is the subject. There is no phase 3 program.
Beyond these, 5 records are indexed. Browse the records