PEG-loxenatide
Polyethylene glycol loxenatide, PEGylated exendin-4 analogue
Written by Aaron CuhaReviewed Sep 2026
Also known as: PEX168, PEG-Loxe, Polyethylene glycol loxenatide injection
Approved in China in 2019 on two placebo-controlled phase 3 trials in 361 and about 360 patients, where it lowered glycated haemoglobin about 1.0 to 1.3 percentage points. Its weight effect in those registration trials was small; the large weight figures come from later single-centre trials at doses well above the licensed ones.
Overview
Polyethylene glycol loxenatide, usually written PEX168 in the trial literature, is a PEGylated analogue of exendin-4 from Hansoh Pharmaceutical. It was approved in China in 2019, which makes it one of the earliest domestically developed weekly GLP-1 agonists to reach a market anywhere.
It has one of the deeper published records on this page. Beyond the two registration trials there are randomised comparisons against insulin glargine and against metformin, a randomised trial in diabetic kidney disease against dapagliflozin, pharmacokinetics in renal impairment, and multiple meta-analyses. That is a body of evidence, though almost all of it is Chinese and much of it single-centre.
The registration doses were 100 and 200 micrograms weekly. Read that number carefully when you meet the weight-loss figures that circulate about this drug, because a 2026 single-centre randomised trial in what its authors call super-obese patients with type 2 diabetes used 300 and 400 micrograms weekly, one and a half to four times the registration doses, and reported weight reductions of 16.34 and 21.14 kg over 24 weeks against 6.75 kg on placebo. Those are dramatic numbers from 105 completers at one centre at unlicensed doses, and the placebo arm losing 6.75 kg tells you the whole trial included an intensive background intervention.
What the registration trials themselves showed was ordinary and solid: about a 1.0 to 1.3 percentage point fall in glycated haemoglobin, mild gastrointestinal reactions, no increase in hypoglycaemia or weight gain, and antidrug antibodies in under 2 to 2.5 percent of patients.
Mechanism of action
An analogue of exendin-4 modified with polyethylene glycol at a defined site. PEGylation increases molecular size and slows renal clearance, converting a peptide that would need twice-daily injection into a once-weekly one. At the receptor it behaves as a GLP-1 receptor agonist: glucose-dependent insulin secretion, glucagon suppression, slowed gastric emptying and reduced appetite. Because clearance is substantially renal, pharmacokinetics in renal impairment have been studied separately. Reported exploratory effects in later Chinese trials include changes in albuminuria, gut microbiota composition and endothelial measures, all of which are secondary or exploratory endpoints rather than demonstrated clinical outcomes.
Human evidence
Two multicentre double-blind placebo-controlled phase 3 registration trials, plus randomised comparisons against insulin glargine, metformin and dapagliflozin, pharmacokinetics in renal impairment, and several meta-analyses. Almost all of it Chinese.
- Phase 3a monotherapy, 361 patients: glycated haemoglobin fell 1.02 and 1.34 percentage points at 100 and 200 micrograms against 0.17 on placebo.
- Phase 3b added to metformin, 44 sites: 1.16 and 1.14 percentage points against a 0.35 point rise on placebo, with the two doses performing identically.
- Antidrug antibodies were reported in 1.2 percent and under 2 percent of patients in the two registration trials, far below the rate seen in the phase 1 of the other PEGylated exenatide on this page.
- In diabetic kidney disease it reduced albuminuria as much as dapagliflozin over 24 weeks, on a surrogate endpoint in 80 completers at one centre.
- The large weight loss figures, 16 to 21 kg over 24 weeks, come from one single-centre single-blind trial at 300 and 400 micrograms weekly, above the registration doses.
What this does not tell you: The registration evidence is 24 weeks of controlled follow-up with an open extension. There is no cardiovascular outcome trial and no renal outcome trial, only albuminuria. The striking weight results are from a single centre, single-blind, at unlicensed doses, with a placebo group that itself lost nearly 7 kg. And every efficacy trial is in Chinese patients, whose baseline body mass index is well below that of Western obesity trial populations.
Reading the research record
The most instructive thing about this compound is what happens to its numbers as you move away from the registration trials.
The phase 3 programme, double-blind, multicentre, placebo-controlled, produced a solid, unremarkable glycaemic drug: about a point of glycated haemoglobin, mild nausea, no hypoglycaemia signal, low immunogenicity, and a weight effect small enough that the add-on trial describes it as an absence of weight gain rather than a weight loss.
The later literature contains far more dramatic figures, and almost all of them come from single-centre trials, open-label or single-blind designs, higher than licensed doses, or retrospective real-world cohorts. The 21 kg weight loss result is the clearest example: single centre, single blind, 400 micrograms weekly, and a placebo arm that lost 6.75 kg on its own.
None of that means the later trials are wrong. It means the effect size you quote depends entirely on which design you quote, and the double-blind multicentre registration trials are the ones with the least room for the result to be produced by the study rather than the drug.
The kidney trial deserves the same reading. Reducing albuminuria as much as dapagliflozin over 24 weeks in 80 completers is a surrogate result. Dapagliflozin has hard renal outcome data behind it. This does not.
A note on what Chinese approval does and does not tell you. China's National Medical Products Administration requires trials in Chinese patients, and the pivotal trials behind these approvals are real randomised controlled trials published in mainstream journals, several of them in Diabetologia, Nature Communications, Diabetes Obesity and Metabolism and the Lancet regional title. What is usually missing compared with the Western incretin programmes is a cardiovascular outcome trial. Semaglutide and liraglutide carry cardiovascular outcome data in tens of thousands of patients followed for years; none of the compounds on this page does. So the correct statement is that these drugs are shown to lower glycated haemoglobin and body weight in Chinese adults over months, not that they are shown to prevent heart attacks. That gap is a real difference in the evidence, and it is separate from the question of whether a Western reader has heard of the drug.
The evidence, charted
Fig. 1 · evidence composition
4of 4 citations (100%) are in people
Every citation cited here is Human work; no other study type is cited on this page. This count is of our own citation list and understates any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 4 distinct years, 2020 to 2026, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Not approved
AU
Not approved
CA
Not approved
Not approved in any of the four jurisdictions shown. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Fig. 4 · dose response
No human dose response curve exists
We draw this figure where the data supports it. For this compound in humans it does not, so the panel stays empty rather than borrowing an animal curve and implying it transfers.
Key studies & citations
- Human2021
Efficacy and safety of polyethylene glycol loxenatide monotherapy in type 2 diabetes patients: A multicentre, randomized, double-blind, placebo-controlled phase 3a clinical trial
361 Chinese patients with inadequate glycaemic control randomised to placebo, 100 or 200 micrograms weekly for 24 weeks, then a 28 week extension. Glycated haemoglobin fell 1.02 percentage points on 100 micrograms and 1.34 on 200 against 0.17 on placebo. 34.7 percent and 46.6 percent reached below 7 percent against 15.7 percent. Nausea occurred in 5.6 and 10.0 percent against none on placebo, vomiting in 2.4 and 8.3 percent against none. Antidrug antibodies developed in 4 patients, 1.2 percent.
Diabetes, Obesity and Metabolism - Human2020
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
The add-on registration trial across 44 Chinese sites, randomised to metformin plus placebo, plus 100 micrograms or plus 200 micrograms, 24 weeks core plus 28 week extension. Glycated haemoglobin fell 1.16 and 1.14 percentage points against a rise of 0.35 on placebo. 37.4 and 40.6 percent reached below 7.0 percent against 16.8 percent. Notably the two doses performed the same, gastrointestinal reactions were mild, hypoglycaemia and weight gain did not increase, anti-drug antibodies appeared in under 2 percent, and no treatment-emergent serious adverse events occurred.
Diabetes, Obesity and Metabolism - Human2026
Effect of polyethylene glycol loxenatide on weight loss in super-obese patients with type 2 diabetes: a randomized controlled trial
Single-centre, single-blind trial, 123 enrolled and 105 completed, randomised to 300 or 400 micrograms weekly or placebo for 24 weeks. Weight fell 16.34 kg on 300 micrograms and 21.14 kg on 400 against 6.75 kg on placebo. Glycated haemoglobin fell 1.02 and 1.34 percentage points against 0.50. Adverse drug reactions reached 36.11 percent on the high dose against 11.43 percent on placebo. These doses are one and a half to four times the registration doses, the trial is single-centre and single-blind, and the placebo arm losing 6.75 kg indicates a substantial background intervention in all groups.
Frontiers in Endocrinology - Human2024
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
Single-centre open-label trial against dapagliflozin. 106 randomised, 80 completed. Urine albumin to creatinine ratio fell 29.3 percent on PEG-loxenatide against 31.8 percent on dapagliflozin over 24 weeks, a difference that was not significant. Glycated haemoglobin fell almost identically in both arms. Triglycerides fell more on PEG-loxenatide. Gastrointestinal adverse events were more common on PEG-loxenatide. Albuminuria is a surrogate marker; no kidney outcome such as dialysis, transplantation or doubling of creatinine was measured.
Frontiers in Endocrinology
Frequently asked questions
Is PEG-loxenatide approved?
Yes, in China, since 2019, for type 2 diabetes. It has no approval in the United States, United Kingdom, Australia or Canada and no Western regulatory filing has been located.
How much weight does it cause people to lose?
In the double-blind multicentre registration trials, very little; the add-on trial describes the finding as no increase in weight gain rather than a weight loss. Figures of 16 to 21 kg come from a single-centre single-blind trial using 300 and 400 micrograms weekly, above the registration doses, in which the placebo group also lost 6.75 kg.
How does it compare to semaglutide?
No randomised head to head has been published. Retrospective two-centre comparisons exist in the Chinese literature. On the registration data alone, the glycaemic effect is in the same range as other weekly agonists and the weight effect is smaller than semaglutide's.
Does it protect the kidneys?
One single-centre open-label trial in 80 completers found it reduced urinary albumin to creatinine ratio as much as dapagliflozin over 24 weeks. That is a surrogate marker. No trial has measured whether it prevents progression to dialysis, transplantation or doubling of serum creatinine.
Why do the 100 and 200 microgram doses work the same?
That is what the add-on to metformin registration trial found, 1.16 against 1.14 percentage points of glycated haemoglobin. In the monotherapy trial the higher dose did better, 1.34 against 1.02, at the cost of roughly double the nausea and vomiting. A flat dose-response in one of two pivotal trials is a real feature of this drug's record.