Metabolic & Weight Management

Exenatide

Exenatide is a synthetic copy of a peptide found in the venom of the Gila monster, a desert lizard. The peptide happens to fit the human GLP-1 (glucagon-like peptide-1) receptor, and, the part that turned a curiosity into a medicine, it resists the enzyme that clears the human hormone within minutes. It became the first drug of the class, FDA-approved in 2005 as Byetta for type 2 diabetes, and every human citation on file is randomised, including EXSCEL, a placebo-controlled cardiovascular outcomes trial in 14,752 people. EXSCEL established that exenatide does not raise cardiovascular risk; it missed superiority at p=0.06, and the label carries no cardiovascular indication.

Last updated 12 August 2026

Studied forGlycaemic control research · Cardiovascular outcome research · Body weight research

Evidence on fileFDA-approved · 2 randomised human trials

Strongest sourceEffects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes (New England Journal of Medici… (randomised human trial)

Mechanism

Activates the GLP-1 receptor, raising glucose-dependent insulin secretion, suppressing glucagon, and slowing gastric emptying.

Regulatory status

Approved by the FDA. Marketed as BYETTA, EXENATIDE. Earliest approval 2005-04-28. Application NDA021773, ANDA206697.

An approval grades as rung 1 on this site, because 21 CFR 314.126 requires adequate and well-controlled human investigations and one cannot be granted without them. It covers specific indications and doses, though, and does not transfer to other uses of the same molecule.

Reported effects

What sources associate with this compound. Reported categories, not outcomes we have graded — each would need its own citation and rung.

Glycaemic control research
Cardiovascular outcome research
Body weight research

Figures

Every figure below is replotted by this site from values published in the cited paper's text or tables — the numbers are the study's, the drawing is ours, and the evidence rung on each image is the rung of its source.

HbA1c change by exenatide dose at 30 weeks — Week 30, Mean HbA1c change from baseline (percentage points) by dose twice daily (µg) — Data: DeFronzo et al. 2005, Diabetes Care (exenatide added to metformin, 30 weeks) · n=336 randomised (272 completed) across 82 US centres, all on maximum-dose metformin, baseline HbA1c 8.2%. Dose 0 µg = placebo. Published values are +0.08 ± 0.10%, -0.40 ± 0.11% and -0.78 ± 0.10%.

Reaching HbA1c 7% or below at 30 weeks — exenatide — Week 30, Participants reaching HbA1c 7% or below (%) by treatment — Data: DeFronzo et al. 2005, Diabetes Care (exenatide added to metformin, 30 weeks) · n=336, all on maximum-dose metformin. Same trial as the dose-response figure; these are the responder proportions published in the abstract, evaluable-patient analysis.

Cardiovascular events on weekly exenatide — EXSCEL — Median 3.2 years, Participants with a primary event (%) by treatment — Data: Holman et al. 2017, NEJM (EXSCEL cardiovascular outcomes) · n=14752 with type 2 diabetes, median follow-up 3.2 years; 839 vs 905 events (3.7 vs 4.0 per 100 person-years). Exenatide was noninferior for safety but not superior for efficacy (p=0.06) — the gap shown here is not a significant difference.

Dosing on file unverified

5 - 10 mcg, 2x/day

Carried from a source that labels it unverified, and reproduced with that label attached. A record of what is reported, not a recommendation. No citation on this page establishes it.

Half-life, storage & sport

Elimination half-life: 2.4 hours (human, SC) — study. BYETTA FDA prescribing information, section 12.3.

The half-life on file is 2.4 h, measured subcutaneously. On the schedule this record states — twice daily — each dose has fallen to 3.1% of its own peak by the time the next is given. Nothing accumulates, and there is no loading phase to run.

Dosed twice daily over 2 d, each dose normalised to the first peak.

The rise is not modelled and the axis is not a blood level. No absorption rate constant and no volume of distribution are on file, so each dose appears at full height the instant it is given, and the axis is percent of this compound's own peak.

Literature on file 3

human RCT
Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes (New England Journal of Medicine 2017, cited 1886x) graded on: names a randomised controlled trial — the indexed publication type — “Randomized Controlled”
human RCT
Effects of Exenatide (Exendin-4) on Glycemic Control and Weight Over 30 Weeks in Metformin-Treated Patients With Type 2 Diabetes (Diabetes Care 2005, cited 1240x) graded on: names a randomised controlled trial — the indexed publication type — “Randomized Controlled”
human RCT
FDA approval NDA021773, ANDA206697 graded on: an FDA approval (NDA021773, ANDA206697), which requires adequate and well-controlled human investigations — “NDA021773, ANDA206697”

Identity

Space-filling 3D model of Exenatide, carbon grey, nitrogen blue, oxygen red — Built from the SMILES on this record — the atoms and bonds are exact. The shape is **one computed low-energy pose**, not a measured structure: a flexible peptide in solution has no single conformation, and where the SMILES leaves a stereocentre undefined the pose commits to one arbitrarily. The skeletal formula below claims connectivity and nothing more, which is what we actually know.

2D chemical structure of Exenatide — Built from the SMILES on this record — the atoms and bonds are exact. The shape is **one computed low-energy pose**, not a measured structure: a flexible peptide in solution has no single conformation, and where the SMILES leaves a stereocentre undefined the pose commits to one arbitrarily. The skeletal formula below claims connectivity and nothing more, which is what we actually know.

Molecular weight: 4187
Molecular formula: C184H282N50O60S
PubChem CID: 16157882
UniProt: P26349
ChEMBL: CHEMBL414357
InChI key: HTQBXNHDCUEHJF-XWLPCZSASA-N
Sequence: HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS
SMILES: CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N)C(=O)NCC(=O)NCC(=O)N3CCC[C@H]3C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N4CCC[C@H]4C(=O)N5CCC[C@H]5C(=O)N6CCC[C@H]6C(=O)N[C@@H](CO)C(=O)N)NC(=O)[C@H](CC7=CC=CC=C7)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC8=CC=CC=C8)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CC9=CN=CN9)N
InChI: InChI=1S/C184H282N50O60S/c1-16-94(10)147(178(289)213-114(52-58-144(257)258)163(274)218-121(73-101-77-195-105-39-24-23-38-103(101)105)168(279)215-116(68-90(2)3)165(276)205-107(41-26-28-61-186)158(269)219-122(75-134(189)243)154(265)198-79-135(244)196-83-139(248)231-63-30-43-129(231)175(286)225-127(87-238)174(285)223-125(85-236)155(266)200-80-136(245)202-96(12)181(292)233-65-32-45-131(233)183(294)234-66-33-46-132(234)182(293)232-64-31-44-130(232)176(287)222-124(84-235)150(190)261)229-170(281)119(71-99-34-19-17-20-35-99)217-166(277)117(69-91(4)5)214-159(270)108(42-29-62-194-184(191)192)212-177(288)146(93(8)9)228-151(262)95(11)203-156(267)111(49-55-141(251)252)208-161(272)112(50-56-142(253)254)209-162(273)113(51-57-143(255)256)210-164(275)115(59-67-295-15)211-160(271)110(47-53-133(188)242)207-157(268)106(40-25-27-60-185)206-172(283)126(86-237)224-167(278)118(70-92(6)7)216-169(280)123(76-145(259)260)220-173(284)128(88-239)226-180(291)149(98(14)241)230-171(282)120(72-100-36-21-18-22-37-100)221-179(290)148(97(13)240)227-138(247)82-199-153(264)109(48-54-140(249)250)204-137(246)81-197-152(263)104(187)74-102-78-193-89-201-102/h17-24,34-39,77-78,89-98,104,106-132,146-149,195,235-241H,16,25-33,40-76,79-88,185-187H2,1-15H3,(H2,188,242)(H2,189,243)(H2,190,261)(H,193,201)(H,196,244)(H,197,263)(H,198,265)(H,199,264)(H,200,266)(H,202,245)(H,203,267)(H,204,246)(H,205,276)(H,206,283)(H,207,268)(H,208,272)(H,209,273)(H,210,275)(H,211,271)(H,212,288)(H,213,289)(H,214,270)(H,215,279)(H,216,280)(H,217,277)(H,218,274)(H,219,269)(H,220,284)(H,221,290)(H,222,287)(H,223,285)(H,224,278)(H,225,286)(H,226,291)(H,227,247)(H,228,262)(H,229,281)(H,230,282)(H,249,250)(H,251,252)(H,253,254)(H,255,256)(H,257,258)(H,259,260)(H4,191,192,194)/t94-,95-,96-,97+,98+,104-,106-,107-,108-,109-,110-,111-,112-,113-,114-,115-,116-,117-,118-,119-,120-,121-,122-,123-,124-,125-,126-,127-,128-,129-,130-,131-,132-,146-,147-,148-,149-/m0/s1

Notes unverified prose

FDA-approved

Not on file 1

1 of the 8 fields we track hold nothing on this record, and each says why. A blank field is a bug; a named absence is a finding.

CAS registry numbernothing we hold supplies it

Each field links to every other record missing the same thing. The full ledger holds 765 gaps across 163 records.

At a glance

Strongest rung: human RCT
Citations: 3
Regulatory: FDA approved
Route: Subcutaneous
Declared gaps: 1

Running this

GLP-1 and incretin

How the class is run, with the source of every schedule beside it.

Citations by rung

human RCT3

Strongest wins, never an average.