Oxyntomodulin

OXM, glucagon-37, enteroglucagon (older term); analogues: OPK-88003 (LY2944876 / TT401), cotadutide (MEDI0382, discontinued), survodutide (BI 456906), mazdutide (IBI362 / LY3305677), pemvidutide (ALT-801), efinopegdutide (MK-6024) — all "GLP-1/glucagon dual agonists" inspired by oxyntomodulin

Metabolic & weight

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Summary

Class: Naturally occurring 37-amino-acid gut hormone from the proglucagon precursor: the full glucagon sequence plus an 8-amino-acid C-terminal tail. Analogues are synthetic peptides engineered for balanced GLP-1 and glucagon receptor activity and long half-life
Mechanism: Activates both the GLP-1 receptor (less eating, more insulin) and the glucagon receptor (more energy expenditure, more fat burning in the liver) — a combination that lowers weight more than appetite suppression alone and improves fatty liver
Routes studied: Intravenous infusion and subcutaneous injection (native hormone, human research); subcutaneous once-weekly (analogues, Phase 2–3)
Half-life: Native OXM ~12 minutes (DPP-4 and neprilysin); analogues engineered for weekly dosing
Storage: Research reagent / investigational products only
Regulatory status: Native hormone not approved anywhere. Mazdutide approved in China (2025) for weight management †; other analogues in Phase 3

Doses are as reported in studies or by the community — never recommendations.

1What it is

Oxyntomodulin was identified in the early 1980s as a glucagon-like material from the gut ("enteroglucagon") that inhibited acid secretion by the stomach's oxyntic glands — hence the name. It is produced by the same intestinal L cells that release GLP-1 and PYY, from the same proglucagon gene, and rises after meals in proportion to calories eaten. Chemically it is the 29-amino-acid glucagon molecule with an extra 8-residue tail, which lets it bind the GLP-1 receptor as well as the glucagon receptor, though with lower potency at each than the dedicated hormones.

In the mid-2000s a London group showed that giving oxyntomodulin to volunteers cut food intake, and that four weeks of pre-meal injections produced modest weight loss while also raising energy expenditure — a combination GLP-1 alone does not offer. Because the native peptide lasts minutes, the pharmaceutical industry instead built long-acting "dual " that copy the idea: survodutide, mazdutide, pemvidutide and others. These are properly synthetic drugs, several of them in or through Phase 3; they are covered here because oxyntomodulin is their template and the words are used interchangeably online. Community/self-directed use of native oxyntomodulin: essentially none documented. Some dual agonists circulate in grey markets as "research chemicals"; there is no published data on such use.

2How it's thought to work

GLP-1 receptor. reduces appetite via hypothalamic and brainstem circuits, slows gastric emptying, boosts glucose-dependent insulin release.

Glucagon receptor. increases hepatic fat oxidation and energy expenditure, promotes lipolysis and raises satiety independently; on its own it would raise blood glucose, but the GLP-1 component offsets this.

Net effect. weight loss driven by both eating less and burning slightly more, with marked reductions in liver fat — the reason several dual have been tested in MASH (fatty liver disease).

Gastric acid and motility. OXM inhibits acid secretion and slows gastric emptying, part of the "ileal brake" with PYY and GLP-1.

The natural gut hormone that first showed the idea works: one peptide acting at both the GLP-1 and the glucagon receptor, reducing intake and raising energy use at once.Schematic — not to scale

3What the research shows

Food intake and weight loss with native oxyntomodulin

Cohen 2003 (J Clin Endocrinol Metab): a 90-minute OXM infusion in 13 healthy volunteers reduced buffet intake by ~19%. Wynne 2005 (Diabetes): 26 overweight or obese volunteers self-injected OXM 400 nmol or saline before meals three times daily for 4 weeks; weight fell 2.3 kg versus 0.5 kg, with reduced energy intake. Wynne 2006 (Int J Obes): the same protocol increased activity-related energy expenditure by ~26% — the key finding that distinguished OXM from GLP-1 and launched the dual-agonist concept. All small, short, single-centre. [1][2][3]

Combination infusions mimicking bariatric surgery

The GOP infusion (GLP-1 + oxyntomodulin + PYY) given subcutaneously for 4 weeks in people with obesity and prediabetes/diabetes produced ~4.4 kg weight loss and improved glucose tolerance (Tan 2017 and Behary 2019, Diabetes Care). [5]

Synthetic GLP-1/glucagon dual agonists

- Survodutide (Boehringer/Zealand): Phase 2 in obesity reported up to ~19% weight loss at 46 weeks on 4.8 mg weekly (le Roux 2024, Lancet Diabetes Endocrinol); Phase 2 in MASH showed 83% of patients with histological improvement (Sanyal 2024, NEJM). Phase 3 SYNCHRONIZE programme read out 2025–2026 †. - Mazdutide (Innovent/Lilly): Phase 3 GLORY-1 in Chinese adults with obesity reported ~14–15% weight loss at 48 weeks on 6 mg (Ji 2025, NEJM); approved in China in 2025 for weight management †. Higher 9 mg dose under study. - Cotadutide (AstraZeneca): Phase 2 showed glucose and liver-fat benefits with ~5% weight loss (Nahra 2021, Diabetes Care); discontinued 2023. - OPK-88003 (OPKO): Phase 2b in type 2 diabetes, 30 weeks, HbA1c −1.3% and weight −4.4 kg versus −0.1% and −1.8 kg with placebo (company release, 2019); not advanced further †. - Pemvidutide (Altimmune) and efinopegdutide (Merck): Phase 2 data in MASH and obesity 2023–2025, with weight loss ~10–15% and large liver-fat reductions †. [6][7][8][9]

Graded C/D

Animal and mechanistic

Rodent studies show OXM's anorectic effect requires the GLP-1 receptor while its energy-expenditure effect requires the glucagon receptor (Kosinski 2012, Obesity); OXM protects islets and improves lipid handling in diet-induced obesity models. [4]

4Reported side effects and interactions

Literature-reported

Literature (native OXM). mild nausea in a minority of volunteers; no serious events in the small trials.

Literature (dual agonists). GI effects dominate — nausea, vomiting, diarrhoea, constipation — at rates similar to or somewhat higher than GLP-1 during titration, with higher discontinuation at top doses in some trials; increased heart rate (the glucagon component adds a few beats per minute beyond GLP-1 agonists); transient rises in liver enzymes in some studies; the class-level GLP-1 cautions (pancreatitis, gallbladder disease, thyroid C-cell rodent signal, delayed gastric emptying) apply.

Community-reported

none documented for native OXM; anecdotal grey-market use of dual agonists is not characterised in any published source.

Theoretical. chronic glucagon-receptor agonism could raise glucose in people with poor beta-cell reserve, lower amino-acid levels and increase muscle protein breakdown; trials monitor lean mass. Glucagon receptor activation also raises hepatic FGF21 — probably beneficial, but long-term effects unknown.

Interactions. additive with insulin and sulfonylureas (hypoglycaemia); delayed absorption of oral medicines; not for use in pregnancy.

Markers researchers commonly monitor

Based on the dual-agonist trial protocols and glucagon physiology:

Marker	Why it's watched
HbA1c and fasting glucose	to confirm the GLP-1 component is offsetting the glucagon component's glucose-raising effect.
Liver enzymes (ALT/AST) and liver fat (MRI-PDFF or FibroScan CAP)	the liver is a primary target and transient enzyme rises have been reported.
Resting heart rate and blood pressure	glucagon agonism raises heart rate more than GLP-1 alone.
Lipase and amylase	pancreatitis signal, if abdominal pain.
Lipid panel	usually improves.
Body composition (DEXA) and plasma amino acids	glucagon receptor agonism increases amino-acid catabolism; lean-mass preservation is a stated trial concern.
Serum FGF21	a research marker of hepatic glucagon-receptor activity.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Native oxyntomodulin exists only as a research-grade peptide for laboratory and clinical-study use; it has no pharmaceutical presentation and no self-administered dose. The dual are investigational or (in China) prescription pens that require no . The site calculator is not applicable.

6Commonly studied alongside

Semaglutide and tirzepatide (comparators and the drugs the dual agonists aim to beat), retatrutide (adds GIP to the GLP-1/glucagon pair), PYY3-36 (GOP combination), glucagon itself, teduglutide (fellow proglucagon product), cagrilintide and amylin (alternative partners for GLP-1 in multi-hormone therapy).

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Native OXM not approved. No GLP-1/glucagon dual agonist FDA-approved as of this review; survodutide, mazdutide, pemvidutide in Phase 3 †
European Union	Not authorised; investigational
United Kingdom	Not licensed; investigational
Australia	Not approved
South Africa	Not registered
Sport	Not specifically listed by WADA; GLP-1 agonists not prohibited as of 2026 †; non-approved analogues would fall under S0

8Open questions

Does the energy-expenditure effect seen with native OXM persist with chronic dual-agonist dosing in humans, or is weight loss mostly from reduced intake?
Do dual preserve lean mass better or worse than GLP-1 monotherapy?
Long-term cardiovascular safety of sustained glucagon-receptor agonism (heart rate, blood pressure).

9References

1Cohen MA et al. (2003). Oxyntomodulin suppresses appetite and reduces food intake in humans. J Clin Endocrinol Metab. PubMed · DOI
2Wynne K et al. (2005). Subcutaneous oxyntomodulin reduces body weight in overweight and obese subjects: a double-blind, randomized, controlled trial. Diabetes. PubMed · DOI
3Wynne K et al. (2006). Oxyntomodulin increases energy expenditure in addition to decreasing energy intake in overweight and obese humans: a randomised controlled trial. Int J Obes. PubMed · DOI
4Kosinski JR et al. (2012). The glucagon receptor is involved in mediating the body weight-lowering effects of oxyntomodulin. Obesity. PubMed · DOI
5Behary P et al. (2019). Combined GLP-1, oxyntomodulin, and peptide YY improves body weight and glycemia in obesity and prediabetes/type 2 diabetes: a randomized, single-blinded, placebo-controlled study. Diabetes Care. PubMed · DOI
6le Roux CW et al. (2024). Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial. Lancet Diabetes Endocrinol. DOI
7Sanyal AJ et al. (2024). A phase 2 randomized trial of survodutide in MASH and fibrosis. NEJM. PubMed · DOI
8Ji L et al. (2025). Mazdutide for adults with obesity (GLORY-1). NEJM. PubMed
9Nahra R et al. (2021). Effects of cotadutide on metabolic and hepatic parameters in adults with overweight or obesity and type 2 diabetes. Diabetes Care. PubMed · DOI
10OPKO Health (2019). OPKO reports additional oxyntomodulin OPK-88003 results from Phase 2b diabetes and obesity trial (company press release). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

forum threads →

community protocols include this →

Threads and protocols are visible to members. Joining is free.

Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

30 Oct 2026Profile published — awaiting medical review

Licensed CC BY-NC-SA 4.0. Found an error? Report it · Editorial standards — corrections are logged here.