Polyethylene glycol loxenatide
A PEGylated exenatide analogue injected once a week, approved in China for type 2 diabetes
Polyethylene glycol loxenatide is a GLP-1 receptor agonist built from exenatide, the first drug of its class, with a polyethylene glycol chain attached so that one injection lasts a week. China's medicines regulator approved it for type 2 diabetes in 2019. Its phase 3 trials, all run in China, found clear drops in blood sugar against placebo, and later smaller trials have pushed the dose higher to test weight loss. It has no US or EU approval.
Used in human trials: 100 µg or 200 µg, Once weekly, Subcutaneous (Trial: type 2 diabetes, monotherapy (phase 3a)) Details ↓
Recommended Dosing
Used in human trials
There is no FDA label. A label from outside the US exists (see the regulatory status on this page) but was not read for this page: these are amounts given in published trials, not recommendations.
Work out syringe units → · New to syringes? · All dosing data ↓
What is it?
GLP-1 is a gut hormone released after meals. It tells the pancreas to release insulin when blood sugar is high, damps glucagon, slows the stomach and reduces appetite. The natural hormone lasts only minutes, so drug makers have spent two decades stretching it out. Exenatide, a GLP-1 receptor agonist first found in Gila monster venom, was the first approved; polyethylene glycol loxenatide is a Chinese descendant of it. A 2023 meta-analysis describes it as exenatide with a changed chemical structure and a longer half-life, and the polyethylene glycol (PEG) chain is what lets it be given once a week.
In China it is an approved medicine. The national regulator announced the approval on May 7, 2019, for adults with type 2 diabetes, used with diet and exercise either alone or with metformin; press coverage noted that the clinical trial application had been accepted twelve years earlier. A 2023 trial report gives 0.1 mg and 0.2 mg weekly as the approved doses, and a 2024 health technology assessment counted it among seven GLP-1 receptor agonists marketed in China. It is not approved by FDA and has no entry in the European Medicines Agency's list.
The approval rests on two placebo-controlled phase 3 trials. In 361 people treated with diet alone, 24 weeks of 100 µg or 200 µg a week lowered HbA1c by 1.02 and 1.34 percentage points against 0.17 on placebo, and 35% and 47% reached an HbA1c under 7% against 16%. Added to metformin in a second trial, both doses cut HbA1c by about 1.15 points while it rose slightly on placebo. Nausea and vomiting were the common side effects, more often at 200 µg, and fewer than 3% of patients made antibodies against the drug.
Since approval, Chinese centres have compared it with other treatments. Against insulin glargine in 78 people on metformin it kept glucose in the target range for more of the day. Against dapagliflozin in diabetic kidney disease it cut urine albumin by a similar amount, about 30%, with a similar HbA1c fall. A two-centre records study that matched 510 pairs found the same HbA1c drop as semaglutide 1.0 mg over two years but less weight loss. Meta-analyses of the randomised trials agree it lowers blood sugar, with weight loss mainly in people who were obese to begin with.
Weight has become the newer question. The approved doses produce little weight change in people of normal weight, so trials have tried more. In 156 overweight or obese patients, 0.3 mg a week for 16 weeks took off 7.5 kg against 3.0 kg on metformin. In a single-blind trial in 123 patients with very severe obesity, 300 µg and 400 µg a week for 24 weeks gave losses of about 16 and 21 kg against 7 kg on placebo, at the cost of more gastrointestinal reactions. These are small single-centre studies, and none of the higher doses is approved.
Two large retrospective cohorts from six Chinese hospitals reported fewer heart attacks, strokes and cardiovascular deaths, and fewer serious kidney events, in people prescribed it. Such studies cannot rule out that healthier patients were the ones given the drug, and in one of them the heart signal disappeared after matching. A placebo-controlled cardiovascular safety trial, BALANCE-3, has published its protocol. Until it reports, the firm evidence is about blood sugar.
Mechanism of Action
Polyethylene glycol loxenatide activates the GLP-1 receptor, as exenatide does; the attached polyethylene glycol slows its clearance enough for weekly dosing.
Glucose-dependent insulin
GLP-1 receptor activation raises insulin release when glucose is high and lowers glucagon, so it seldom causes low blood sugar on its own.
Weekly action
The polyethylene glycol chain slows removal; after one dose the half-life is about five days, longer when the kidneys work less well.
Stomach and appetite
Slower stomach emptying and reduced appetite explain both the nausea early in treatment and the weight loss seen at higher doses.
Published Research
These are studies of polyethylene glycol loxenatide read from their PubMed abstracts: the two phase 3 trials, two pharmacology studies, later randomised and single-arm trials in China, two retrospective cohorts and three meta-analyses. Every trial was run in Chinese patients.
Phase 3a: alone against placebo
361 people with type 2 diabetes not controlled by diet were randomised to placebo or 100 µg or 200 µg weekly. At 24 weeks HbA1c fell 1.02 and 1.34 points against 0.17 on placebo; nausea affected 5.6% and 10.0% on the two doses and vomiting 2.4% and 8.3%, against none on placebo. Six patients stopped for adverse events.
Phase 3b: added to metformin
At 44 sites, patients uncontrolled on at least 1,500 mg of metformin a day added placebo or 100 µg or 200 µg weekly. HbA1c fell about 1.15 points on either dose and rose 0.35 on placebo at 24 weeks; 37% and 41% reached HbA1c under 7% against 17%. Hypoglycaemia and weight gain did not increase, and under 2% formed antibodies.
Kidney function and drug levels
In 23 people given one 200 µg injection, the half-life was 121 hours with normal kidneys, 117 hours with mild impairment and 163 hours with moderate impairment, and total exposure doubled in the moderate group. The authors suggest a dose change may be needed there. Side effects were mostly mild stomach upsets; one serious event occurred.
No interaction with warfarin
16 healthy men took one warfarin dose before and after five weekly 200 µg injections. Blood levels of both warfarin forms and its effect on clotting time (INR and prothrombin time) were unchanged, with all ratios inside the standard equivalence range.
Higher dose for weight against metformin
156 overweight or obese patients were randomised 2:1 to 0.3 mg weekly or metformin 1,500 mg for 16 weeks. Weight fell 7.52 kg (8.4%) against 2.96 kg (3.0%); 62% against 25% lost at least 5%. Glucose control was about equal, and adverse events were similar (46% against 44%). The report notes that the approved doses are 0.1 and 0.2 mg.
Very severe obesity with diabetes
In a single-centre, single-blind trial of 123 patients, 300 µg or 400 µg weekly for 24 weeks reduced weight by 16.3 and 21.1 kg against 6.8 kg on placebo, and HbA1c by 1.02 and 1.34 points against 0.50. Drug reactions, mainly gastrointestinal, occurred in 25% and 36% against 11%; 105 patients finished.
Diabetic kidney disease, against dapagliflozin
106 patients with mild-to-moderate diabetic kidney disease were randomised to this drug or dapagliflozin; 80 finished. Urine albumin-to-creatinine ratio fell 29.3% and 31.8% at 24 weeks, a non-significant difference, with matching HbA1c falls of about 1.3 points. Triglycerides fell more on this drug; stomach side effects were more common.
Glucose monitoring against insulin glargine
78 patients aged 45 or over on metformin were randomised to this drug or insulin glargine for 24 weeks. Over the last two weeks, continuous monitoring showed 13.4 percentage points more time in the 3.9 to 10.0 mmol/L range, lower mean glucose and less swing, with time spent low no different.
Body composition over 12 weeks
In 100 patients who added 0.2 mg weekly to their usual treatment (no control group), HbA1c fell from 8.8% to 6.9% and visceral fat area from 120 to 114 cm², with a 0.8 kg weight loss. Lean mass measured by bioelectrical impedance did not change.
Added to metformin and insulin in overweight patients
100 overweight or obese patients on metformin and insulin were randomised to add this drug or not for six months. The add-on group lost more weight and had larger falls in fasting and after-meal glucose, HbA1c and insulin resistance. The abstract does not state the dose.
Small trial in obesity with diabetes
40 obese patients were randomised to metformin with or without this drug. Fasting and after-meal glucose and triglycerides fell more, and HDL cholesterol rose more, with the add-on; weight loss grew with time on treatment and was largest after seven months.
Records comparison with semaglutide
510 matched pairs starting 200 µg of this drug or semaglutide 1.0 mg weekly in two Chinese centres were followed for 24 months. HbA1c fell about 2.0 and 2.2 points, not significantly different. Semaglutide gave 3.6 kg more weight loss and larger LDL and blood pressure falls; stomach symptoms were more frequent with semaglutide in the first 3 months.
Cardiovascular events in a large cohort
Of 12,341 patients with diabetes and heart disease or risk factors in six hospitals, 1,282 took this drug. Over a median four years the combined rate of heart attack, stroke or cardiovascular death was 4.0% against 11.4% in patients on other incretin-based drugs (hazard ratio 0.68). Patients were found retrospectively with a language-model screen.
Kidney outcomes in a large cohort
3,305 patients with diabetes, reduced kidney function and high cardiovascular risk were followed for a median 36 months. Use of the drug was linked to about half the risk of the main kidney outcome, before and after matching; a lower cardiovascular event rate in the whole cohort did not survive matching, so the authors call it exploratory.
Planned cardiovascular safety trial (BALANCE-3)
A published protocol for a multicentre, double-blind trial randomising people with type 2 diabetes to 0.2 mg weekly or placebo, with two years of follow-up. Its main outcome is the first heart attack, stroke or cardiovascular death, and it is designed to show the drug does not raise that risk unacceptably. No results were found.
Meta-analysis of six trials
Six randomised trials with 1,248 participants: added to metformin it lowered fasting glucose, HbA1c (by about 1.0 point) and after-meal glucose, and as monotherapy it beat placebo. Weight fell about 5.5 kg in obese patients but not in others. Nausea and vomiting were more common, significantly so at 200 µg with metformin.
Meta-analysis of eighteen trials
Eighteen trials with 2,166 patients, including Chinese-language databases: the drug lowered HbA1c, fasting and two-hour glucose, BMI and body weight against controls, but on its own did not change cholesterol, triglycerides or blood pressure.
Which dose? A trial sequential analysis
Pooled trials found 100 µg lowered HbA1c by 0.86 points against placebo without more adverse events overall. The 200 µg dose lowered glucose no further but nearly tripled the risk of gastrointestinal side effects, so the authors favour 100 µg.
Dosing Data
China has approved 0.1 mg and 0.2 mg once a week (PMID 36777344); the Chinese label itself was not read for this page. These rows are the amounts given in published trials, as their abstracts state them. The 300 and 400 µg doses are trial doses for weight, not approved.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Polyethylene glycol loxenatide is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
An arithmetic example, not a recommendation: a 5 mg vial mixed with 2 mL of bacteriostatic water holds 2,500 mcg per mL, so every 10 units on a U-100 insulin syringe hold 250 mcg. 100 µg, the first amount in the “Trial: type 2 diabetes, monotherapy (phase 3a)” row (100 µg or 200 µg) is 4.0 units (0.040 mL). If your vial or water differ, the numbers change: use the reconstitution calculator.
Source: dose: Used in human trials, PMID 32965075 (Dosing Data below); vial and water: the calculator's default example, not a vial size we have a source for.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Polyethylene glycol loxenatide, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Polyethylene glycol loxenatide stays intact once mixed.
How it is taken
As it was given in human studies: Subcutaneous (Once weekly; Trial: type 2 diabetes, monotherapy (phase 3a)).
For injection technique, sites and needle disposal, see the mixing guide.
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: a half-life of about 121 hours in people with normal kidney function. After about five half-lives almost none is left.
How long the doses were given: Trial: type 2 diabetes, monotherapy (phase 3a): 24 weeks, then a 28-week extension; Trial: type 2 diabetes, added to metformin (phase 3b): 24 weeks, then a 28-week extension; Trial: weight loss in overweight or obese type 2 diabetes: 16 weeks.
When effects appear: unknown; no source on this page gives a time to effect for Polyethylene glycol loxenatide. Results reported in the studies are under Published Research.
Source: half-life: PMID 31396983; Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Nausea and vomiting, the most common effects, more frequent at 200 µg than 100 µg (PMIDs 32965075, 38567590); More gastrointestinal reactions at the higher weight-loss doses of 300 and 400 µg (PMID 41694563); Antibodies against the drug in fewer than 3% of patients (PMIDs 32965075, 32744358); No rise in hypoglycaemia when added to metformin (PMID 32744358). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Polyethylene glycol loxenatide. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the trials and cohorts above”).
Interactions
- warfarin: no effect on R- or S-warfarin exposure or on INR and prothrombin time after weekly 200 µg doses in 16 healthy men
Every peptide's record, with its source: the interaction matrix.
Source: human study, PMID 39607179.
Checking what you bought
Unknown: no published independent test of Polyethylene glycol loxenatide products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Not FDA Approved. Elsewhere: approved in China (NMPA, May 2019). Sport: Unsettled (S0 may apply).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the trials and cohorts above.
Contraindications & Cautions
The Chinese label was not read for this page. These cautions follow from the studies.
Legal Status
Polyethylene glycol loxenatide is approved in China and not in the US or the EU.
Frequently Asked Questions
?What is polyethylene glycol loxenatide?
A GLP-1 receptor agonist for type 2 diabetes, made by modifying exenatide and attaching a polyethylene glycol chain so it can be injected once a week. It is also called PEX168 or PEG-Loxe.
?Where is it approved?
In China, since 2019, for adults with type 2 diabetes alone or with metformin. It is not approved by FDA and has no EU authorisation.
?How well does it lower blood sugar?
In the phase 3 trials, 24 weeks of 100 or 200 µg a week lowered HbA1c about 1.0 to 1.3 points more than placebo, alone or with metformin. Meta-analyses found 200 µg lowered glucose no more than 100 µg but caused more nausea.
?Does it cause weight loss?
At the approved doses, mainly in people who start out obese. Small Chinese trials of 300 and 400 µg a week reported larger losses, but those doses are not approved.
?How does it compare with semaglutide?
A two-centre records study found the same HbA1c fall as semaglutide 1.0 mg over two years, with less weight loss and fewer early stomach symptoms. No randomised head-to-head trial was found.
?Does it protect the heart or kidneys?
Two retrospective Chinese cohorts reported fewer events, but such studies can be biased by who receives the drug, and one heart signal vanished after matching. A randomised outcome trial has been designed.
References
- [other] Yicai (第一财经), May 7, 2019: report of the National Medical Products Administration notice approving Hansoh Pharma's polyethylene glycol loxenatide injection for adults with type 2 diabetes. Read October 29, 2026. https://www.yicai.com/news/100182433.html
- [other] European Medicines Agency, medicines list, and Drugs@FDA (openFDA): no record for polyethylene glycol loxenatide (searched October 29, 2026).
- [clinical-trial] Shuai Y, et al. "Efficacy and safety of polyethylene glycol loxenatide monotherapy in type 2 diabetes patients: A multicentre, randomized, double-blind, placebo-controlled phase 3a clinical trial." Diabetes Obes Metab, 2021;23(1):116-124. PMID: 32965075.
- [clinical-trial] Gao F, et al. "Efficacy and safety of polyethylene glycol loxenatide as add-on to metformin in patients with type 2 diabetes: A multicentre, randomized, double-blind, placebo-controlled, phase 3b trial." Diabetes Obes Metab, 2020;22(12):2375-2383. PMID: 32744358.
- [clinical-trial] Wang J, et al. "Polyethylene glycol loxenatide (PEX168) in subjects with renal impairment: A pharmacokinetic study." Br J Clin Pharmacol, 2019;85(12):2714-2720. PMID: 31396983.
- [clinical-trial] Zhou H, et al. "Warfarin pharmacokinetics and pharmacodynamics are not affected by concomitant administration of the long-acting GLP-1 receptor agonist polyethylene glycol loxenatide." Int J Clin Pharmacol Ther, 2025;63(2):47-53. PMID: 39607179.
- [clinical-trial] Cai H, et al. "Short-term effect of polyethylene glycol loxenatide on weight loss in overweight or obese patients with type 2 diabetes: An open-label, parallel-arm, randomized, metformin-controlled trial." Front Endocrinol (Lausanne), 2023;14:1106868. PMID: 36777344.
- [clinical-trial] Liu Z, et al. "Effect of polyethylene glycol loxenatide on weight loss in super-obese patients with type 2 diabetes: a randomized controlled trial." Front Endocrinol (Lausanne), 2026;17:1689040. PMID: 41694563.
- [clinical-trial] Cao Y, et al. "Efficacy and safety of polyethylene glycol loxenatide in treating mild-to-moderate diabetic kidney disease in type 2 diabetes patients: a randomized, open-label, clinical trial." Front Endocrinol (Lausanne), 2024;15:1387993. PMID: 39099671.
- [clinical-trial] Zhang S, et al. "Efficacy of polyethylene glycol loxenatide versus insulin glargine on glycemic control in patients with type 2 diabetes: a randomized, open-label, parallel-group trial." Front Pharmacol, 2023;14:1171399. PMID: 37214446.
- [clinical-trial] Gu R, et al. "Polyethylene Glycol Loxenatide Selectively Reduces Adiposity While Preserving Lean Body Mass in Type 2 Diabetes: A 12-Week Clinical Study." Diabetes Metab Syndr Obes, 2026;19:592044. PMID: 42453280.
- [clinical-trial] Song X, et al. "Clinical Efficacy of Polyethylene Glycol Loxenatide in the Treatment of Obese or Overweight Patients with Type 2 Diabetes Mellitus." J Coll Physicians Surg Pak, 2023;33(12):1390-1394. PMID: 38062594.
- [clinical-trial] Li XY, et al. "Effect of polyethylene Glycol Loxenatide (long-acting GLP-1RA) on lipid, glucose levels and weight in type 2 diabetes mellitus patients with obesity." Eur Rev Med Pharmacol Sci, 2022;26(21):7996-8003. PMID: 36394750.
- [pubmed] Yu Z, et al. "Real-world glycemic control, exploratory cardiorenal indicators, and safety of polyethylene glycol loxenatide versus semaglutide in type 2 diabetes patients: a Chinese two-center retrospective cohort study." Front Endocrinol (Lausanne), 2026;17:1756581. PMID: 41953701.
- [pubmed] Li J, et al. "Once-weekly glucagon-like peptide receptor agonist polyethylene glycol loxenatide protects against major adverse cardiovascular events in patients with type 2 diabetes: a multicenter ambispective cohort study (FLYING trial)." MedComm (2020), 2025;6(2):e70094. PMID: 39949982.
- [pubmed] Ye J, et al. "Real-world renoprotective effects of polyethylene glycol-loxenatide in type 2 diabetes: a multicenter, ambispective cohort study." Signal Transduct Target Ther, 2026;11(1). PMID: 42897130.
- [review] Salamah HM, et al. "Efficacy and safety of polyethylene glycol loxenatide in type 2 diabetic patients: a systematic review and meta-analysis of randomized controlled trials." Sci Rep, 2023;13(1):19041. PMID: 37923756.
- [review] Liu Y, et al. "Efficacy of polyethylene glycol loxenatide for type 2 diabetes mellitus patients: a systematic review and meta-analysis." Front Pharmacol, 2024;15:1235639. PMID: 38469407.
- [review] Liu P, et al. "Is polyethylene glycol loxenatide 100 μg the preferred glucagon-like peptide-1 receptor agonist for type 2 diabetes mellitus? A meta-analysis and trial sequential analysis." Eur Rev Med Pharmacol Sci, 2024;28(6):2272-2287. PMID: 38567590.
- [pubmed] Xie Y, et al. "Impact of polyethylene glycol loxenatide on cardiovascular outcomes in patients with type 2 diabetes: study protocol for a multicentre, randomised, double-blind, placebo-controlled trial (BALANCE-3)." BMJ Open, 2023;13(5):e069080. PMID: 37192802.
- [pubmed] Xie Z, et al. "Health Technology Assessment: Evaluation of 7 Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus." Risk Manag Healthc Policy, 2024;17:1053-1067. PMID: 38680477.
- [pubmed] Xu Y, et al. "Efficacy and safety of different once-weekly glucagon-like peptide-1 receptor agonists-A systematic review and Bayesian network meta-analysis." Diabetes Res Clin Pract, 2025;230:112954. PMID: 42618994.
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026. The Chinese approval comes from a Yicai report of the NMPA notice (May 7, 2019) and trial reports; US and EU status from Drugs@FDA (openFDA) and the EMA medicines list, searched the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.