C-peptide
The piece cut from proinsulin that shows how much insulin the body still makes
C-peptide is the 31-amino-acid segment cut out of proinsulin when insulin is made, and it is released in equal amounts with insulin. Doctors measure it to judge how much insulin a person still makes, which helps tell type 1 from type 2 diabetes. People with type 1 diabetes make almost none, and small Swedish trials gave it back by injection or infusion, reporting better nerve, kidney and blood-flow measures. It has never been approved as a medicine.
Used in human trials: 1.5 mg or 4.5 mg a day, Divided into four doses a day, Subcutaneous (Type 1 diabetic neuropathy (139 completed, 6 months)) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
Work out syringe units → · New to syringes? · All dosing data ↓
What is it?
The pancreas makes insulin as a single chain, proinsulin. Before release, the middle of that chain is cut out, leaving insulin's two chains joined and freeing a 31-amino-acid fragment called the connecting peptide, or C-peptide. The two leave the beta cell together, one molecule of C-peptide for every molecule of insulin. That makes C-peptide the best available measure of the body's own insulin secretion, including in people already treated with insulin. It is cleared at a steadier rate and over a longer time than insulin, and it can be measured in a blood sample or a spot urine sample as a ratio to creatinine.
Its everyday use is sorting out what kind of diabetes someone has. American and European diabetes guidance now uses cut-offs: a level below 0.2 nmol/L points to type 1 diabetes and one above 0.6 nmol/L to type 2. Reviews of clinical practice find the test most useful three to five years after diagnosis, when a person who still makes substantial insulin probably has type 2 or a monogenic form, while absent C-peptide at any point confirms that the person needs insulin. One practical review recommends a glucagon stimulation test as the best balance of sensitivity and convenience. The weak point is the assay: C-peptide tests from different manufacturers still give noticeably different results, and a 2025 review called for standardisation before the guideline cut-offs can be applied with confidence.
In type 1 diabetes, even a little remaining C-peptide matters. In a Scottish cohort of 6,076 people followed for about five years, those with C-peptide of 200 pmol/L or more, compared with those below 5 pmol/L, used 27% less insulin, had lower HbA1c, were admitted with ketoacidosis less than half as often and had about half the odds of new retinopathy. Protection against serious hypoglycaemia showed up at much lower levels, down to the limit of detection. The authors note what this means for trials of treatments meant to preserve or restore islet function in type 1 diabetes.
Outside type 1 diabetes, C-peptide has been studied as a marker of insulin resistance and risk, with mixed results. In 5,153 adults without diabetes from the US NHANES-3 survey, those in the highest quartile of fasting C-peptide had a 60% higher adjusted risk of cardiovascular death and a 72% higher risk of death overall than those in the lowest. In 399 people newly diagnosed with type 2 diabetes in Sweden, the highest quartile carried 2.75 times the risk of death but no more cardiovascular events. A 2023 meta-analysis of 16 observational studies found no link with cardiovascular events in the cohort studies and a positive one only in cross-sectional studies.
Because people with type 1 diabetes lack C-peptide, a Swedish research programme tested whether giving it back does anything. Short infusions at physiological amounts improved autonomic nerve tests, skin capillary flow and blood flow and pumping in the heart muscle in small randomised crossover studies. Given by injection for one to three months, it reduced albumin leaking into the urine and improved nerve conduction in people with early neuropathy. The largest trial, 139 people with neuropathy treated for six months, found sensory nerve conduction improved within both C-peptide groups, more patients responding than on placebo, and better vibration sense within the treated groups. A long-acting pegylated form, a modified molecule listed under References, was then given weekly to 250 people for a year: it did not improve nerve conduction, though vibration perception improved against placebo. No C-peptide product reached approval.
How C-peptide would act on nerves and vessels is unsettled. Earlier work reported that it stimulates the enzymes Na+,K+-ATPase and endothelial nitric oxide synthase, and a 2020 review notes that whether it works through a receptor, which has not been identified, or by some other route is still an open question. We found no human half-life figure for C-peptide itself in the abstracts read.
Mechanism of Action
C-peptide is cut from proinsulin and secreted with insulin in equal amounts. Its main use is as a measure of insulin output; whether it also acts as a hormone in its own right is still debated.
A record of insulin secretion
Because it leaves the beta cell with insulin, one molecule for one, its level in blood or urine shows how much insulin the pancreas is making, including in people already treated with insulin.
Nerve enzyme activity
Studies cited by the Swedish trial group report that C-peptide stimulates Na+,K+-ATPase and endothelial nitric oxide synthase, two enzyme systems that matter for nerve function and are deficient in type 1 diabetes.
Small-vessel blood flow
Infused in people with type 1 diabetes, it increased nutritive capillary flow in the skin of the feet and the heart muscle's blood flow response, toward values seen in people without diabetes.
No confirmed receptor
A receptor for C-peptide has not been identified, and a 2020 review leaves open whether its effects are receptor-mediated at all.
Published Research
Studies of C-peptide itself, read from their PubMed abstracts: the randomised trials that gave it to people with type 1 diabetes, the large studies that measured it, and reviews of its clinical use. Trials of drugs that aim to preserve C-peptide measure it as an outcome but study those drugs, so they are not carded here; the long-acting pegylated form is a modified molecule and is listed under References.
Six months of replacement in neuropathy
In a double-blind, placebo-controlled trial at five Swedish centres, 139 people with type 1 diabetes and neuropathy completed 6 months of C-peptide 1.5 or 4.5 mg a day in four subcutaneous doses. Sensory nerve conduction improved similarly within both C-peptide groups, more patients responded with a gain over 1.0 m/s than on placebo, and in the least affected patients conduction improved by 1.0 m/s against placebo; neurological impairment scores and vibration perception improved within the treated groups.
Three months in early nerve dysfunction
In 46 people with type 1 diabetes and no symptoms of neuropathy, 3 months of C-peptide (600 nmol per 24 hours in four subcutaneous doses) improved sural sensory conduction velocity by 2.7 m/s against placebo, about 80% of the initial deficit, and improved vibration perception; cold and heat perception did not change.
Albumin in the urine and nerve function
In a double-blind crossover study of 21 people with type 1 diabetes and microalbuminuria, 3 months of C-peptide with their usual insulin lowered urinary albumin excretion from 58 to 34 µg/min, while it tended to rise on placebo; heart rate variability improved in those with autonomic neuropathy and thermal thresholds improved.
One month with insulin: the kidney
Nine people with type 1 diabetes given insulin plus an equal molar amount of C-peptide for a month, against nine on insulin alone, had albumin excretion fall by 40% and 55% at 2 and 4 weeks, glomerular filtration fall by 6%, less leakage across the blood-retinal barrier and slightly lower HbA1c.
A three-hour infusion and autonomic nerves
In 12 people with type 1 diabetes and neuropathy, a 3-hour intravenous C-peptide infusion raised blood levels into the normal range and increased respiratory heart rate variability from 13% to 20% against no change with saline; sensory thresholds and nerve conduction did not change.
Heart muscle blood flow on PET
In a randomised crossover study of 10 young men with type 1 diabetes, a 2-hour C-peptide infusion raised adenosine-stimulated myocardial blood flow 35% more than saline, to values like those of healthy controls, and increased ejection fraction by 5% and stroke volume by 7%.
Heart muscle function on echocardiography
In eight people with type 1 diabetes, who had lower diastolic velocity and myocardial blood volume than controls, a 1-hour C-peptide infusion increased systolic and diastolic myocardial velocities by 12% and raised myocardial blood volume and a blood flow index, in a double-blind crossover against saline.
Skin capillary blood flow
In 19 people with type 1 diabetes, a 60-minute C-peptide infusion increased capillary blood cell velocity in the feet from 147 to 167 µm/s, to the level of healthy subjects, with no change on saline and none in healthy volunteers; blood pressure, heart rate and glucose did not change.
Hypoglycaemia came on faster
In seven people with type 1 diabetes exposed to insulin-induced hypoglycaemia with and without C-peptide given in equal molar amounts to insulin for 3 hours, blood glucose fell faster and further with C-peptide, with no difference in glucagon or other counter-regulatory hormones.
Residual C-peptide in 6,076 people
In a Scottish type 1 diabetes cohort followed for 5.2 years, C-peptide of 200 pmol/L or more, against below 5 pmol/L, went with a 27% lower insulin dose, lower HbA1c, a hazard ratio of 0.44 for ketoacidosis admission and an odds ratio of 0.51 for new retinopathy; fewer serious hypoglycaemic episodes were seen at much lower levels.
A risk marker in people without diabetes
Among 5,153 adults without diabetes in NHANES-3 followed to 2006, the highest quartile of fasting C-peptide had adjusted hazard ratios of 1.60 for cardiovascular death and 1.72 for death overall against the lowest, and predicted these better than insulin or glucose-based measures.
Newly diagnosed type 2 diabetes
In 399 people under 65 with newly diagnosed type 2 diabetes in the Skaraborg register, the highest C-peptide quartile had 2.75 times the risk of death from any cause, but C-peptide was not associated with cardiovascular events or retinopathy.
Meta-analysis: cardiovascular events
Pooling 16 observational studies with 4,852 cardiovascular events, cohort and case-control studies showed no association between serum C-peptide and cardiovascular events (RR 1.02), while cross-sectional studies showed a positive one (OR 1.35).
How clinicians should use the test
C-peptide is made in equal amounts to insulin and is the best measure of endogenous insulin secretion; its main role is classifying and managing insulin-treated patients, most useful 3 to 5 years after diagnosis, and it can be measured on a spot urine sample as a C-peptide to creatinine ratio.
A practical review of testing
Compares urinary, fasting and stimulated tests and recommends glucagon stimulation; a level below 0.2 nmol/L is associated with type 1 diabetes, and C-peptide is excreted at a more constant rate over a longer time than insulin.
A call to standardise the assay
ADA and EASD guidance uses C-peptide cut-offs (below 0.2 nmol/L suggests type 1, above 0.6 nmol/L type 2), but results from different assay manufacturers still vary significantly, which limits the cut-offs; the authors urge standardised measurement.
What its physiology looks like now
C-peptide's effects vary with tissue, concentration and the presence of insulin; it may have therapeutic potential for diabetic nerve and vessel damage, but whether it acts through a receptor, whose existence is uncertain, is unresolved.
Dosing Data
The amounts below are the doses and infusion rates given to people with type 1 diabetes in the published trials carded above. C-peptide has no approved product and no label.
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 C-peptide 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. 1.5 mg, the first amount in the “Type 1 diabetic neuropathy (139 completed, 6 months)” row (1.5 mg or 4.5 mg a day) is 60.0 units (0.600 mL). If your vial or water differ, the numbers change: use the reconstitution calculator.
Source: dose: Used in human trials, PMID 17192336 (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 C-peptide, 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 C-peptide stays intact once mixed.
How it is taken
As it was given in human studies: Subcutaneous (Divided into four doses a day; Type 1 diabetic neuropathy (139 completed, 6 months)); Intravenous (Continuous infusion; Autonomic nerve study (12 people)).
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: Type 1 diabetic neuropathy (139 completed, 6 months): 6 months; Early nerve dysfunction (46 completed): 3 months; Microalbuminuria, crossover (21 people): 3 months.
When effects appear: unknown; no source on this page gives a time to effect for C-peptide. 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: Blood glucose fell faster and further during insulin-induced hypoglycaemia when C-peptide was infused with insulin, in a 7-person study; No other adverse effects are described in the trial abstracts read; their full safety data were not read here. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping C-peptide. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the abstracts of the trials above, which say little about safety”).
Interactions
Unknown: a PubMed search for human interaction studies of C-peptide (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of C-peptide 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; it checks the measured mass against C-peptide's expected mass, 3,020.3 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not approved as a medicine anywhere in the sources read). Sport: Prohibited (S0 catch-all).
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 abstracts of the trials above, which say little about safety.
Contraindications & Cautions
There is no label.
Legal Status
C-peptide is measured in clinical laboratories every day but has never been approved as a medicine.
Frequently Asked Questions
?What is C-peptide?
The 31-amino-acid fragment cut from proinsulin when insulin is made. It is released with insulin, one molecule for each insulin molecule, so its level shows how much insulin the body is making.
?What does a C-peptide test show?
How much insulin your own pancreas still makes. Guidance uses below 0.2 nmol/L as pointing to type 1 diabetes and above 0.6 nmol/L to type 2, though assays from different makers still disagree.
?Can C-peptide be taken as a treatment?
Only in research. Swedish trials gave it to people with type 1 diabetes and reported better nerve conduction, less albumin in the urine and better small-vessel blood flow, but the studies were small, a later long-acting version did not improve nerve conduction, and no product was approved.
?Does a high C-peptide mean higher risk?
In some studies. High fasting C-peptide went with more deaths in US adults without diabetes and in newly diagnosed type 2 diabetes, but a meta-analysis of cohort studies found no link with cardiovascular events.
?Why does a little C-peptide matter in type 1 diabetes?
In a cohort of 6,076 people, those still making some had lower insulin doses, lower HbA1c and fewer ketoacidosis admissions, retinopathy and serious hypoglycaemic episodes.
References
- [clinical-trial] Ekberg K, et al. "C-Peptide replacement therapy and sensory nerve function in type 1 diabetic neuropathy." Diabetes Care, 2007;30(1):71-6. PMID: 17192336.
- [clinical-trial] Ekberg K, et al. "Amelioration of sensory nerve dysfunction by C-Peptide in patients with type 1 diabetes." Diabetes, 2003;52(2):536-41. PMID: 12540632.
- [clinical-trial] Johansson BL, et al. "Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with Type 1 diabetes mellitus." Diabet Med, 2000;17(3):181-9. PMID: 10784221.
- [clinical-trial] Johansson BL, et al. "Influence of combined C-peptide and insulin administration on renal function and metabolic control in diabetes type 1." J Clin Endocrinol Metab, 1993;77(4):976-81. PMID: 8408474.
- [clinical-trial] Johansson BL, et al. "C-peptide improves autonomic nerve function in IDDM patients." Diabetologia, 1996;39(6):687-95. PMID: 8781764.
- [clinical-trial] Johansson BL, et al. "C-peptide improves adenosine-induced myocardial vasodilation in type 1 diabetes patients." Am J Physiol Endocrinol Metab, 2004;286(1):E14-9. PMID: 12954595.
- [clinical-trial] Hansen A, et al. "C-peptide exerts beneficial effects on myocardial blood flow and function in patients with type 1 diabetes." Diabetes, 2002;51(10):3077-82. PMID: 12351450.
- [clinical-trial] Forst T, et al. "Biological activity of C-peptide on the skin microcirculation in patients with insulin-dependent diabetes mellitus." J Clin Invest, 1998;101(10):2036-41. PMID: 9593759.
- [clinical-trial] Oskarsson P, et al. "Effects of C-peptide on insulin-induced hypoglycaemia and its counterregulatory responses in IDDM patients." Diabet Med, 1997;14(8):655-9. PMID: 9272591.
- [pubmed] Jeyam A, et al. "Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications." Diabetes Care, 2021;44(2):390-398. PMID: 33303639.
- [pubmed] Patel N, et al. "Fasting serum C-peptide levels predict cardiovascular and overall death in nondiabetic adults." J Am Heart Assoc, 2012;1(6):e003152. PMID: 23316320.
- [pubmed] Pikkemaat M, et al. "C-peptide concentration, mortality and vascular complications in people with Type 2 diabetes. The Skaraborg Diabetes Register." Diabet Med, 2015;32(1):85-9. PMID: 25354243.
- [review] Jahromi MK, et al. "The association of serum C-peptide with the risk of cardiovascular events: a meta-analysis and systematic review." Diabetol Metab Syndr, 2023;15(1):168. PMID: 37568168.
- [review] Jones AG, et al. "The clinical utility of C-peptide measurement in the care of patients with diabetes." Diabet Med, 2013;30(7):803-17. PMID: 23413806.
- [review] Leighton E, et al. "A Practical Review of C-Peptide Testing in Diabetes." Diabetes Ther, 2017;8(3):475-487. PMID: 28484968.
- [review] Schleicher E, et al. "Call for Standardization of C-Peptide Measurement." J Diabetes Sci Technol, 2025:19322968251362848. PMID: 40781799.
- [review] Vejrazkova D, et al. "Insights into the physiology of C-peptide." Physiol Res, 2020;69(Suppl 2):S237-S243. PMID: 33094622.
- [clinical-trial] Wahren J, et al. "Long-Acting C-Peptide and Neuropathy in Type 1 Diabetes: A 12-Month Clinical Trial." Diabetes Care, 2016;39(4):596-602. PMID: 26884473.
- [other] UniProt P01308 (INS_HUMAN), propeptide residues 57-87, C peptide; read October 28, 2026. https://www.uniprot.org/uniprotkb/P01308/entry
- [other] PubChem CID 16157840, Human c-peptide: formula C129H211N35O48, molecular weight 3020.3. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/16157840
Sources & Citations
Studies were read from their PubMed abstracts on October 28, 2026; the sequence is from UniProt and the formula from PubChem. C-peptide has no label.
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.