# Davalintide: Evidence, Mechanism & Legal Status

> A clinical monograph on davalintide (AC2307) — Amylin Pharmaceuticals' second-generation amylin-mimetic peptide. Robust rodent fat-loss data, one unreported Phase 2 trial, and a program discontinued in 2010.

*Published 2026-06-30 · Updated 2026-07-01 · By Marcus Feld, PharmD, BCPS*

The short answer
Davalintide (AC2307) is a second-generation amylin-mimetic peptide with **robust rodent fat-loss pharmacology but no published human efficacy** — so its highest evidence grade is **C (preclinical only)**. A single Phase 2 obesity trial completed in 2009 but its results were never released, and Amylin Pharmaceuticals discontinued the molecule in 2010 because it offered no advantage over pramlintide. It is a never-approved, not-for-human-use investigational drug.[1](https://peptidevox.com/#r1)[5](https://peptidevox.com/#r5)

Davalintide (AC2307; INN davalintide) is a synthetic amylin analog engineered by Amylin Pharmaceuticals as a 32-amino-acid chimera of rat amylin and salmon calcitonin, designed to be a longer-acting, more potent successor to the company's marketed amylin drug pramlintide.[1](https://peptidevox.com/#r1)[3](https://peptidevox.com/#r3) Its rodent pharmacology was clean and compelling; its human story is a cautionary one. This monograph separates the two.

*This article is informational and editorial content for research and educational purposes only. It is not medical advice, not a protocol to follow, and not a sourcing guide. Davalintide is a discontinued investigational drug with no marketing approval anywhere in the world and no legal pathway for human use; any "research-chemical" sale is explicitly not for human use. Dosing figures are reported strictly as seen in the trial registry and literature for completeness — never as guidance. Consult a licensed clinician before any health decision.*

## What is davalintide and how does it work?

Davalintide (CAS 863919-85-1; UNII 668U999F9T; DrugBank DB14956) is a 32-residue peptide amide of molecular weight roughly 3624 Da, built as a chimera of the primary sequences of rat amylin and salmon calcitonin.[5](https://peptidevox.com/#r5)[7](https://peptidevox.com/#r7) Structurally it is assembled from three modules — an N-terminal loop, an α-helical mid-region derived from calcitonin, and a C-terminal tail — and it retains the conserved Cys2–Cys7 disulfide bridge and an amidated C-terminus, both required for full biological activity.[3](https://peptidevox.com/#r3) The salmon-calcitonin helix is the engineering trick: it stabilizes receptor binding and gives the molecule a markedly longer functional duration than native amylin.[3](https://peptidevox.com/#r3)

Pharmacologically, davalintide is a non-selective amylin agonist, often classified as a dual amylin and calcitonin receptor agonist (DACRA). Amylin receptors are heterodimers of the calcitonin-receptor core plus a receptor-activity-modifying protein. Davalintide binds across this family with high affinity — reported amylin-receptor IC₅₀ near 0.04 nM and calcitonin-receptor IC₅₀ near 0.06 nM — and activates cAMP through the calcitonin receptor more potently than native amylin.[6](https://peptidevox.com/#r6)[7](https://peptidevox.com/#r7) In rat membrane and insulinoma assays it was essentially equipotent with native rat amylin, indicating the engineering preserved amylin's core signaling.[3](https://peptidevox.com/#r3)

The mechanism behind its appetite effect is central, not peripheral. Like amylin, davalintide reduces food intake through the area postrema in the dorsal hindbrain: lesioning the area postrema abolished the anorectic effect of both davalintide and amylin, and the two peptides activated overlapping brainstem nuclei by c-Fos mapping.[1](https://peptidevox.com/#r1) Beyond satiety it reproduces amylin's glucoregulatory triad — slowed gastric emptying (rat subcutaneous ED₅₀ ≈ 2.3 µg/kg) and suppression of glucagon secretion — which limits the postprandial glucose rise.[2](https://peptidevox.com/#r2) Its defining property is prolonged action despite a short circulating half-life: slower receptor dissociation translated into suppression of dark-cycle feeding for about 23 hours versus roughly 6 hours for amylin, and c-Fos expression sustained about 8 hours versus 2 hours.[1](https://peptidevox.com/#r1) Even so, this fell well short of a once-weekly profile, so the human program relied on twice-daily subcutaneous dosing.[4](https://peptidevox.com/#r4)

## What is the evidence by indication?

The evidence picture is lopsided: extensive rodent pharmacology, and a single human trial whose results were never released. Every indication below is best understood as animal-model evidence, graded C for human use.

  Davalintide evidence by indication

    IndicationBest evidenceGrade (human)

    Obesity / weight lossRobust rodent fat-loss data; one Phase 2 RCT (n=273) completed but results never posted; program discontinuedC (preclinical)
    Satiety / food-intake suppressionDose-dependent, area-postrema-mediated suppression in rats; no rodent malaise signalC (preclinical)
    Type 2 diabetes / glucoregulationSlowed gastric emptying and glucagon suppression in rats; no human glycemic trial reportedNone (preclinical only)

The rodent weight-loss data are the strongest part of the file. In diet-induced-obese and lean rats, sustained subcutaneous davalintide produced dose-dependent, durable weight loss up to about 22% of body weight over eight weeks that was fat-specific and lean-sparing — selective fat-mass reduction with lean mass preserved or even increased at higher doses.[1](https://peptidevox.com/#r1) Crucially, metabolic rate was preserved during active weight loss, and animals shifted food preference away from high-fat palatable chow.[1](https://peptidevox.com/#r1) At anorectic doses davalintide did not increase kaolin (clay) consumption — a rodent proxy for nausea and conditioned taste aversion — and did not alter locomotor activity, suggesting the appetite reduction was a genuine satiety effect rather than sickness behavior.[1](https://peptidevox.com/#r1)

The single human trial tells the opposite story. [NCT00785408](https://clinicaltrials.gov/study/NCT00785408) was a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study of subcutaneous AC2307 (three active dose levels versus placebo, twice daily) in 273 obese or overweight adults, run from December 2008 to September 2009. Primary endpoints were body-weight change and safety/tolerability at 24 weeks. The study completed, but no results were ever posted to the registry, and no peer-reviewed efficacy publication exists.[4](https://peptidevox.com/#r4) Amylin discontinued davalintide in 2010.[5](https://peptidevox.com/#r5) Independent industry analysis frames the failure plainly: the weight loss was modest relative to the nausea burden, and the molecule was no better than the already-approved pramlintide — an unfavorable efficacy-to-tolerability ratio.[8](https://peptidevox.com/#r8) The rodent glucoregulatory effects similarly supported a theoretical glucose-lowering role, but no human glycemic trial was conducted or reported.[2](https://peptidevox.com/#r2)

Proven vs hyped
Proven: robust *animal* fat-loss pharmacology — graded C for human use. Hyped or unsupported: any claim of human weight-loss efficacy, of which there is none published. The developer walked away in 2010 because the molecule was no better than pramlintide. The amylin thesis itself was later vindicated not by davalintide but by the long-acting analog cagrilintide.[8](https://peptidevox.com/#r8)[9](https://peptidevox.com/#r9)

## What doses appear in the literature?

Reported strictly as information, not a protocol — davalintide is discontinued and unapproved, and there is no legitimate human-use regimen.[4](https://peptidevox.com/#r4) In the Phase 2 trial, davalintide was given by subcutaneous injection twice daily at three escalating dose levels (low, middle, high) versus matched placebo over a 24-week treatment period; the exact milligram doses were never disclosed in the public registry record, and full dosing and pharmacokinetic data were never published.[4](https://peptidevox.com/#r4) Preclinical rat work used acute intraperitoneal bolus dosing and chronic subcutaneous osmotic-minipump infusion over up to eight weeks, with gastric-emptying potency reported at a subcutaneous ED₅₀ near 2.3 µg/kg.[1](https://peptidevox.com/#r1)[2](https://peptidevox.com/#r2) As a peptide, davalintide is not orally bioavailable — it is proteolyzed in the gut and must be administered parenterally. No reconstitution protocol exists in approved labeling because the drug was never approved; any reconstitution guidance circulating with research-chemical vials is unverified and outside any regulatory standard.[11](https://peptidevox.com/#r11)

## How safe is davalintide?

Human adverse-event data are not publicly available, because the Phase 2 trial's safety and tolerability results were never posted.[4](https://peptidevox.com/#r4) What can be stated is structural. Nausea and gastrointestinal upset are the dose-limiting effect of the amylin and calcitonin agonist class, and davalintide's program was explicitly terminated for an unfavorable efficacy-to-tolerability ratio — the weight loss did not justify the side-effect burden and was no better than pramlintide.[8](https://peptidevox.com/#r8) Notably, the favorable rodent picture — no kaolin-eating and no locomotor suppression at anorectic doses — did not generalize to humans, a reminder that a clean preclinical tolerability profile does not guarantee human tolerability.[1](https://peptidevox.com/#r1)

Theoretical and class-level risks remain unquantified for davalintide specifically. Chronic calcitonin-receptor agonism raises questions about calcium and bone, and a salmon-calcitonin-derived peptide carries generic concerns about immunogenicity and anti-drug antibodies, alongside injection-site reactions common to peptide drugs.[3](https://peptidevox.com/#r3) By class analogy, amylin agonists slow gastric emptying and can alter the absorption rate of orally co-administered drugs, and combined with insulin or insulin secretagogues they raise hypoglycemia risk — extrapolated from pramlintide-class pharmacology, not davalintide-specific data.[2](https://peptidevox.com/#r2) By the same analogy, caution applies in gastroparesis or any condition where delayed gastric emptying is harmful, and in pregnancy and lactation, where there are no data. There are no established label-based contraindications because davalintide was never approved, and any human exposure via unregulated research-chemical channels is of unknown purity and unsafe by default.[11](https://peptidevox.com/#r11)

## What is the FDA and WADA status in 2026?

Davalintide is not an FDA-approved drug. It is a discontinued investigational drug — development was halted by Amylin Pharmaceuticals in 2010 after Phase 2 — with no NDA or BLA, no Orange Book or Purple Book listing, and no place on the FDA's lists of bulk drug substances eligible for compounding under sections 503A or 503B.[5](https://peptidevox.com/#r5) It is sold only as a research-use-only reference peptide labeled not for human use. Under the Federal Food, Drug, and Cosmetic Act, an unapproved peptide marketed for human therapeutic use is misbranded and adulterated, and not-for-human-use labeling does not make consumption lawful.[11](https://peptidevox.com/#r11) It is not a scheduled controlled substance, but that confers no legality for human administration. For athletes, davalintide is not named on the WADA Prohibited List, but as a non-approved substance it is presumptively prohibited at all times under category S0; any tested athlete should treat it as banned and clear it with their anti-doping authority.[11](https://peptidevox.com/#r11) There is no EMA or other major-regulator approval, and the molecule is discontinued globally.

The most useful frame for davalintide in 2026 is comparative. The amylin mechanism it pioneered has since been clinically validated by cagrilintide, a long-acting human amylin analog: in the Phase 3 REDEFINE-1 program, once-weekly cagrilintide 2.4 mg monotherapy produced roughly 11.8% weight loss versus about 2.3% with placebo over 68 weeks, and the fixed-dose CagriSema combination with semaglutide drove more than 20% loss in a majority of participants, with Novo Nordisk filing an FDA application in December 2025.[9](https://peptidevox.com/#r9)[10](https://peptidevox.com/#r10) The contrast — long-acting once-weekly cagrilintide succeeding where short-acting twice-daily davalintide failed — is the central lesson of davalintide's story.

**Bottom line.** Davalintide is a well-characterized but failed second-generation amylin analog: a clean piece of receptor pharmacology with fat-specific, lean-sparing rodent weight loss and preserved metabolic rate, but a molecule that never demonstrated a human benefit worth its tolerability cost — graded C for human use, discontinued, unapproved, and not for human use. Anyone interested in the amylin mechanism for weight management should look to approved or late-stage agents such as pramlintide and cagrilintide/CagriSema under medical supervision, not to davalintide. Regulatory facts here are current as of June 2026 and should be re-verified for any later development.

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Source: https://peptidevox.com/peptide-encyclopedia/davalintide
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