Insulin tregopil
Biocon's swallowed mealtime insulin: how it gets through the gut, what the trials found, and why it has not reached the market
Insulin tregopil (IN-105) is human insulin with a short polyethylene glycol chain attached, made by the Indian company Biocon to be swallowed as a tablet before meals. A fatty-acid salt in the tablet, sodium caprate, helps it cross the gut wall, and like the body's own insulin it reaches the liver first. In trials it acted within about 10 to 20 minutes and wore off in under two hours. In its main phase 2/3 trial it handled the first hour after a meal as well as or better than injected insulin aspart but did not lower HbA1c. It is not approved anywhere.
Used in human trials: 30 mg or 45 mg, Before meals, Oral tablet (Phase 2/3: type 2 diabetes on glargine and metformin (91 randomised)) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
Insulin has always had to be injected, because swallowed protein is digested and too large to cross the gut lining. Insulin tregopil is one of several attempts to get around that. It is ordinary human insulin with a short chain of polyethylene glycol fixed to one lysine near the end of the B chain, which makes it amphiphilic, partly water-loving and partly fat-loving, a property chosen to help it cross membranes. The tablet also contains sodium caprate, a fatty-acid salt that loosens the gut wall for a short time so the insulin can pass. Biocon, an Indian biotechnology company, developed it under the code IN-105.
The case for oral insulin is partly about convenience and partly about where the insulin goes. Insulin made by the pancreas goes straight to the liver through the portal vein, and the liver keeps much of it. Injected insulin enters the general circulation instead, so muscles and fat see more of it than they would naturally. Insulin absorbed from the gut follows the natural route. In dogs with catheters in the portal vein, tregopil absorbed from the intestine reached its peak in about 20 minutes and was back to baseline by about 90 minutes, far faster than injected human insulin, and infused straight into the portal vein it behaved almost exactly like human insulin.
The first published human trial, in 2010, gave single ascending doses before a meal to people with type 2 diabetes poorly controlled on metformin. The rise in blood insulin grew with the dose, and the glucose rise two hours after the meal fell in step, with no clinical hypoglycaemia at any dose. The body's own C-peptide fell as tregopil levels rose, a sign the pancreas was releasing less of its own insulin. A later crossover study looked at timing: taking the tablet 10 to 20 minutes before the meal worked better than 30 minutes, absorption improved with a longer gap since the previous meal, a high-fat meal reduced absorption without blunting the effect much, and a high-fibre meal hardly affected it. A safety study in healthy volunteers found tregopil and its sodium caprate did not meaningfully change how metformin is absorbed.
The main efficacy trial was a 24-week, open-label phase 2/3 study in people with type 2 diabetes already on insulin glargine and metformin. Ninety-one patients were randomised to 30 mg or 45 mg of tregopil at meals or to injected insulin aspart. HbA1c, the main measure, did not improve on either tregopil dose, while it fell by 0.77 percentage points on aspart. Tregopil did better than aspart on the glucose rise in the first hour after a standard meal, and clinically significant hypoglycaemia was about 30% less frequent, but its effect faded too early to control the later part of the meal. The authors described it as ultra-fast and short.
In type 1 diabetes, a phase 1 study gave 37 patients rising fixed doses of up to 60 mg, plus an optional extra 30 mg, before each of three main meals. Peak levels came 15 to 20 minutes after the dose and the glucose effect lasted up to about 105 minutes. Hypoglycaemia did not rise with dose and none was severe, but responses varied widely, and the authors concluded that fixed doses were not a workable stand-alone option, though they cut the need for injected aspart. The registry record says the second part of that trial was never started. An earlier type 1 diabetes study, NCT01035801, was terminated; its record cites an unexpected bioanalytical issue.
Measuring tregopil needed its own test, because most insulin assays either miss it or react to the long-acting glargine that patients also take; Biocon scientists built an ELISA that measures it down to 0.25 ng/mL. A 2023 review by the developers summarises the programme: good early after-meal control, less hypoglycaemia than injected mealtime insulin, and inferior control later in the meal. In the sources read, no regulator has approved tregopil, and the registry shows no phase 3 trial beyond the combined phase 2/3 study.
Mechanism of Action
Insulin tregopil is human insulin with a short PEG chain, swallowed with an absorption enhancer; once absorbed it acts on the insulin receptor exactly as insulin does, but it reaches the liver first.
Getting through the gut
The short PEG chain makes the insulin amphiphilic, and sodium caprate, a permeation enhancer, increases its absorption through the gut into the blood.
Liver first
Absorbed insulin travels through the portal vein to the liver, as the pancreas's own insulin does, instead of flooding the whole body as an injection does.
Fast and brief
Blood levels peak within about 20 minutes and the glucose effect is gone in under two hours, which suits the start of a meal but not its tail.
Published Research
These are studies of insulin tregopil itself, read from their PubMed abstracts: the phase 1 and phase 2/3 human trials, a drug-interaction study, an assay study, a dog study, a manufacturing paper and the developers' 2023 review. All human trials were sponsored by its developer.
Phase 2/3: early meal control, no HbA1c benefit
In 91 people with type 2 diabetes on glargine and metformin, randomised to tregopil 30 mg, 45 mg or insulin aspart for 24 weeks, HbA1c did not fall on tregopil but fell 0.77% on aspart. Tregopil controlled the one-hour glucose excursion after a test meal better than aspart, and significant hypoglycaemia was less frequent (rate ratio 0.69), but later post-meal control was worse.
Phase 1 in type 1 diabetes: not a stand-alone option
Thirty-seven people with type 1 diabetes took fixed ascending doses before three meals a day. Blood levels peaked within 15 to 20 minutes and the glucose effect lasted up to 105 minutes; hypoglycaemia did not increase with dose and none was severe. Variability was high, and fixed doses reduced but did not replace injected aspart.
First dose-ranging study with a meal
People with type 2 diabetes on metformin took placebo then single tablets of increasing strength 20 minutes before a meal. Peak insulin rose with dose and the two-hour glucose rise fell in step; C-peptide fell as tregopil exposure rose, and no clinical hypoglycaemia occurred at any dose.
When to take it, and with what meal
In a placebo-controlled crossover study in type 2 diabetes, taking tregopil 10 to 20 minutes before a meal gave better exposure and glucose lowering than 30 minutes before. Absorption improved as the gap since the last meal grew from 4 to 6 hours; high-fat meals reduced absorption, high-fibre meals barely did, and onset was about 10 minutes.
No meaningful effect on metformin
In a randomised crossover study in healthy volunteers, tregopil with its sodium caprate enhancer did not change metformin exposure in a clinically relevant way, fasting or fed; one peak measure fell just outside the usual equivalence range when fasting and was judged not relevant.
An assay that tells tregopil from glargine
Because most commercial insulin kits miss tregopil or react with insulin glargine, the developers validated an electrochemiluminescent ELISA with a lower limit of 0.25 ng/mL and minimal glargine cross-reactivity, tested on samples from dosed type 1 diabetes patients.
In dogs: fast in, fast out, through the liver
In conscious dogs, tregopil infused into the portal vein behaved almost identically to human insulin. Given into the gut it peaked at about 20 minutes, like inhaled insulin, and returned to baseline in about 90 minutes, against 210 minutes for inhaled and 360 minutes for injected insulin.
A one-pot manufacturing step
The developers combined two manufacturing steps, removing a protecting group from an insulin intermediate and attaching the short methoxy-PEG chain at lysine B29, into a single reaction, and found the product matched tregopil made the conventional way.
The developers' review of the programme
The review describes tregopil as a methoxy-PEG-modified human insulin with sodium caprate, absorbed into the portal circulation. Across trials in type 1 and type 2 diabetes it beat placebo on after-meal glucose, beat aspart mainly in the early post-meal period, and caused less clinically significant hypoglycaemia.
Dosing Data
Insulin tregopil is not approved anywhere. These are the amounts given in its published human trials, as their abstracts state them. They are trial doses in insulin-treated diabetes under study monitoring, not a guide.
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 Insulin tregopil is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
No worked example: none of the doses on this page is a fixed amount in mg or mcg injected under the skin or into a muscle (the routes given are: oral tablet). There is no home-mixing step to show. The reconstitution calculator does the arithmetic for any vial.
Source: the route and amount of each dose row in Dosing Data below.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Insulin tregopil, 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 Insulin tregopil stays intact once mixed.
How it is taken
As it was given in human studies: Oral tablet (Before meals; Phase 2/3: type 2 diabetes on glargine and metformin (91 randomised)).
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: not established by a measurement cited on this entry.
How long the doses were given: Phase 2/3: type 2 diabetes on glargine and metformin (91 randomised): 24 weeks; Phase 1: type 1 diabetes, multiple ascending doses (37 patients): Dose-escalation cohorts; Dose-ranging: type 2 diabetes on metformin: Five sequential periods.
When effects appear: unknown; no source on this page gives a time to effect for Insulin tregopil. Results reported in the studies are under Published Research.
Source: 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: Hypoglycaemia, the expected effect of any insulin; clinically significant episodes were less frequent than with insulin aspart (rate ratio 0.69) (PMID 36352762); In type 1 diabetes, no safety concerns beyond hypoglycaemia, which did not rise with dose and was never severe (PMID 40211481); No clinical hypoglycaemia at single doses up to 30 mg in type 2 diabetes (PMID 20590742); Highly variable absorption from one dose to the next (PMID 40211481). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Insulin tregopil. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the human trials above”).
Interactions
- metformin: a randomised crossover study in healthy volunteers measured the effect of tregopil and its permeation enhancer on metformin pharmacokinetics
Every peptide's record, with its source: the interaction matrix.
Source: human study, PMID 30592549.
Checking what you bought
Unknown: no published independent test of Insulin tregopil 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: In Clinical Trials (Not approved anywhere in the sources read). Sport: Prohibited at all times (S4.4.2).
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 human trials above.
Contraindications & Cautions
No product label exists. These cautions follow from the evidence.
Legal Status
Insulin tregopil is an investigational drug; it is not approved as a medicine anywhere in the sources read.
Frequently Asked Questions
?What is insulin tregopil?
A modified human insulin, with a short polyethylene glycol chain, made by Biocon to be swallowed as a tablet before meals. It is also called IN-105.
?How can insulin work as a pill?
The PEG chain changes how the molecule behaves, and the tablet contains sodium caprate, a permeation enhancer that increases absorption from the gut. The absorbed insulin goes to the liver first, like the body's own insulin.
?Did it work in trials?
Partly. It controlled the first hour after a meal as well as or better than injected insulin aspart and caused less significant hypoglycaemia, but it did not lower HbA1c over 24 weeks, while aspart did.
?How fast does it act?
Onset was about 10 minutes, with peak blood levels at 15 to 20 minutes and an effect lasting up to about 105 minutes.
?Is insulin tregopil approved?
No. It has no approval from the FDA or the EMA in the sources read, and no licensed product exists.
?Who developed it?
Biocon, an Indian biotechnology company, which sponsored the registered trials and wrote the 2023 review of the programme.
References
- [clinical-trial] Lebovitz HE, et al. "Efficacy and safety of Tregopil, a novel, ultra-rapid acting oral prandial insulin analog, as part of a basal-bolus regimen in type 2 diabetes: a randomized, active-controlled phase 2/3 study." Expert Opin Pharmacother, 2022;23(16):1855-1863. PMID: 36352762.
- [clinical-trial] Latres E, et al. "An open-label, multiple ascending dose trial of orally administered insulin Tregopil in patients with type 1 diabetes mellitus to evaluate its pharmacokinetics, pharmacodynamics, safety and tolerability." Diabetes Obes Metab, 2025;27(6):3154-3164. PMID: 40211481.
- [clinical-trial] Khedkar A, et al. "A dose range finding study of novel oral insulin (IN-105) under fed conditions in type 2 diabetes mellitus subjects." Diabetes Obes Metab, 2010;12(8):659-64. PMID: 20590742.
- [clinical-trial] Khedkar A, et al. "Pharmacokinetics and Pharmacodynamics of Insulin Tregopil in Relation to Premeal Dosing Time, Between Meal Interval, and Meal Composition in Patients With Type 2 Diabetes Mellitus." Clin Pharmacol Drug Dev, 2020;9(1):74-86. PMID: 31392840.
- [clinical-trial] Khedkar A, et al. "Impact of Insulin Tregopil and Its Permeation Enhancer on Pharmacokinetics of Metformin in Healthy Volunteers: Randomized, Open-Label, Placebo-Controlled, Crossover Study." Clin Transl Sci, 2019;12(3):276-282. PMID: 30592549.
- [pubmed] Ramaswamy SG, et al. "Development and validation of an electrochemiluminescent ELISA for quantitation of oral insulin tregopil in diabetes mellitus serum." Bioanalysis, 2017;9(13):975-986. PMID: 28692306.
- [pubmed] Gregory JM, et al. "Enterically delivered insulin tregopil exhibits rapid absorption characteristics and a pharmacodynamic effect similar to human insulin in conscious dogs." Diabetes Obes Metab, 2019;21(1):160-169. PMID: 30095210.
- [pubmed] Hazra P, et al. "A novel one-pot de-blocking and conjugation reaction step leads to process intensification in the manufacture of PEGylated insulin IN-105." Bioprocess Biosyst Eng, 2012;35(8):1333-41. PMID: 22453680.
- [review] Joshi S, et al. "Insulin Tregopil: An Ultra-Fast Oral Recombinant Human Insulin Analog: Preclinical and Clinical Development in Diabetes Mellitus." Drugs, 2023;83(13):1161-1178. PMID: 37578592.
Sources & Citations
Every study on this page was read from its PubMed record on October 28, 2026. Regulatory status comes from Drugs@FDA (openFDA) and the EMA medicines list, and trial status from ClinicalTrials.gov, read 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.