Enyglid (Repaglinide)
Oral antidiabetic medicine for type 2 diabetes mellitus
Quick Facts About Enyglid
Key Takeaways About Enyglid
- Mealtime dosing: Enyglid should be taken immediately before or up to 30 minutes before each main meal, and the dose should be skipped if a meal is skipped
- Rapid action: It begins working within 30 minutes and its effect lasts approximately 4 hours, providing flexible mealtime blood sugar control
- Hypoglycemia risk: The most common side effect is low blood sugar (hypoglycemia) – always carry glucose tablets or sugary food
- Avoid gemfibrozil: Enyglid must not be taken together with gemfibrozil, as this combination dramatically increases repaglinide blood levels
- Not for type 1 diabetes: Enyglid is only for type 2 diabetes and should not be used if you have type 1 diabetes or diabetic ketoacidosis
What Is Enyglid and What Is It Used For?
Enyglid (repaglinide) is a prescription oral antidiabetic medicine used to treat type 2 diabetes mellitus in adults. It belongs to the meglitinide class and works by stimulating the pancreas to release insulin at mealtimes, helping to control blood sugar levels after eating.
Enyglid contains the active substance repaglinide, which is classified as a short-acting insulin secretagogue. Unlike sulphonylureas, which stimulate insulin release regardless of blood sugar levels, repaglinide has a glucose-dependent mechanism. This means that its insulin-stimulating effect is more pronounced when blood glucose is elevated, particularly after meals, and diminishes as blood glucose returns to normal levels. This pharmacological property makes Enyglid particularly well-suited for controlling postprandial (after-meal) blood glucose spikes.
Type 2 diabetes mellitus is a chronic metabolic condition characterised by insulin resistance and progressive beta-cell dysfunction. In the early stages, the pancreas compensates by producing more insulin, but over time, beta-cell function declines and blood sugar levels rise. Enyglid addresses this by directly stimulating the beta cells of the pancreas to secrete more insulin, particularly during the period immediately following a meal when blood glucose levels are at their highest.
Enyglid is approved for use in the European Union by the European Medicines Agency (EMA) and is available in several countries worldwide under various brand names, including Prandin and NovoNorm. It may be used as monotherapy when diet and exercise are insufficient to control blood sugar, or it may be used in combination with metformin for patients who are not adequately controlled on either agent alone.
Unlike long-acting sulphonylureas such as glibenclamide or glimepiride, Enyglid has a rapid onset of action (within 30 minutes) and a short duration of effect (approximately 4 hours). This means you take it before each meal rather than once or twice daily, giving you more flexible mealtime glucose control and a potentially lower risk of prolonged hypoglycemia between meals.
Mechanism of action
Repaglinide works by binding to specific receptors on the surface of the insulin-producing beta cells in the pancreas. Specifically, it closes ATP-sensitive potassium (K-ATP) channels in the beta-cell membrane. When these potassium channels close, the cell membrane depolarises, which opens voltage-dependent calcium channels. The resulting influx of calcium ions triggers the exocytosis of insulin-containing granules, releasing insulin into the bloodstream.
The binding site for repaglinide on the K-ATP channel is distinct from that of sulphonylureas, although both classes of drugs ultimately act through the same channel. Repaglinide binds to and dissociates from the receptor more rapidly than sulphonylureas, which contributes to its shorter duration of action and the need for mealtime dosing.
Pharmacokinetics
After oral administration, repaglinide is rapidly and completely absorbed from the gastrointestinal tract. Peak plasma concentrations are reached within approximately 1 hour. The absolute bioavailability is approximately 63%, and the drug is extensively metabolised in the liver primarily by cytochrome P450 enzymes CYP2C8 and CYP3A4. The metabolites are inactive and are excreted primarily through the bile. The elimination half-life is approximately 1 hour, which accounts for the short duration of action and the need to take the medicine before each meal.
What Should You Know Before Taking Enyglid?
Before taking Enyglid, it is essential to inform your doctor about all other medicines you are taking, any liver or kidney problems, whether you are pregnant or planning a pregnancy, and whether you have type 1 diabetes or diabetic ketoacidosis, as these are absolute contraindications.
Enyglid, like all prescription medicines, must be used under medical supervision. Your doctor will assess whether Enyglid is appropriate for you based on your overall health status, other conditions you may have, and other medicines you are taking. Understanding the contraindications, warnings, and precautions is critical to ensuring safe and effective use of this medicine.
Contraindications
Enyglid must not be used in the following situations:
- Hypersensitivity: If you are allergic to repaglinide or any of the excipients in the tablet formulation
- Type 1 diabetes: Enyglid is not effective in type 1 diabetes because this condition involves an absolute lack of insulin-producing beta cells
- Diabetic ketoacidosis: This is a medical emergency that requires insulin treatment, not oral antidiabetic therapy
- Severe liver impairment: Since repaglinide is extensively metabolised in the liver, severe hepatic disease can lead to dangerously elevated blood levels of the drug
- Concomitant use with gemfibrozil: The combination of repaglinide and gemfibrozil is strictly contraindicated due to a severe pharmacokinetic interaction that increases repaglinide exposure by up to 8-fold
Warnings and Precautions
Before and during treatment with Enyglid, several important precautions should be observed:
- Hypoglycemia: Enyglid can cause low blood sugar. The risk is increased by irregular meal patterns, skipping meals, excessive exercise, alcohol consumption, or concurrent use of other blood glucose-lowering medicines. Always carry a source of fast-acting sugar such as glucose tablets
- Hepatic impairment: Patients with mild to moderate liver disease may have higher blood levels of repaglinide and may need lower doses. Regular monitoring of liver function is recommended
- Renal impairment: Although repaglinide is primarily metabolised in the liver, patients with kidney disease should be closely monitored as they may be more susceptible to hypoglycemia
- Surgery and illness: During periods of physiological stress such as surgery, trauma, or acute illness, temporary insulin therapy may be needed instead of Enyglid
- Elderly patients: Clinical experience in patients over 75 years is limited. Dose adjustment should be carried out with particular care in this age group
Enyglid must never be used together with gemfibrozil (a fibrate medicine used to lower cholesterol). This combination increases repaglinide blood levels by up to 8-fold, leading to an extremely high risk of severe and prolonged hypoglycemia. If you need a lipid-lowering fibrate, your doctor should consider alternative treatments.
Pregnancy and Breastfeeding
Enyglid should not be used during pregnancy. There are no adequate clinical studies of repaglinide in pregnant women, and animal studies have shown reproductive toxicity at high doses. If you are planning a pregnancy, become pregnant, or think you may be pregnant while taking Enyglid, you should stop taking it and contact your doctor immediately. Insulin is the recommended treatment for managing diabetes during pregnancy because it provides more predictable blood sugar control and does not cross the placenta to affect the developing baby.
It is not known whether repaglinide passes into human breast milk. Because of the potential risk to the nursing infant, Enyglid should not be used during breastfeeding. Your doctor may switch you to insulin or another suitable treatment during this period.
Driving and operating machinery
Enyglid can cause hypoglycemia, which may impair your ability to concentrate and react. You should be aware of the symptoms of low blood sugar and take precautions before driving or operating dangerous machinery. If you experience frequent hypoglycemic episodes, discuss this with your doctor, as it may affect your fitness to drive.
How Does Enyglid Interact with Other Drugs?
Enyglid interacts with several commonly prescribed medicines. The most critical interaction is with gemfibrozil (contraindicated). Other important interactions include CYP2C8 and CYP3A4 inhibitors, beta-blockers, and certain antibiotics that can increase or decrease repaglinide levels.
Drug interactions with Enyglid can broadly be divided into two categories: pharmacokinetic interactions (where another drug affects the blood levels of repaglinide) and pharmacodynamic interactions (where another drug enhances or reduces the blood sugar-lowering effect). Understanding these interactions is crucial for preventing both dangerous hypoglycemia and unexpected loss of blood sugar control.
Repaglinide is primarily metabolised by cytochrome P450 enzymes CYP2C8 and CYP3A4 in the liver, and it is also a substrate for the organic anion-transporting polypeptide 1B1 (OATP1B1) hepatic uptake transporter. Medicines that inhibit or induce these enzymes and transporters can significantly alter repaglinide blood levels.
Major Interactions
| Drug | Interaction Type | Effect | Recommendation |
|---|---|---|---|
| Gemfibrozil | CYP2C8 + OATP1B1 inhibitor | Increases repaglinide levels up to 8-fold | Contraindicated – do not use together |
| Ciclosporin | CYP3A4 + OATP1B1 inhibitor | Increases repaglinide levels significantly | Avoid; if necessary, close monitoring required |
| Clopidogrel | CYP2C8 inhibitor | Increases repaglinide exposure by approximately 5-fold | Avoid combination or use lowest dose with monitoring |
| Trimethoprim | CYP2C8 inhibitor | Increases repaglinide levels moderately | Use with caution; monitor blood glucose closely |
| Rifampicin | CYP2C8 + CYP3A4 inducer | Decreases repaglinide levels by up to 80% | Avoid; diabetes control may be lost |
Minor Interactions
Several other medicines can have more modest effects on repaglinide blood levels or on blood sugar control in general:
- Clarithromycin, itraconazole, ketoconazole (CYP3A4 inhibitors) – may moderately increase repaglinide levels; monitor blood glucose
- Beta-blockers (e.g., propranolol, metoprolol) – may mask symptoms of hypoglycemia such as tremor and rapid heartbeat; blood glucose monitoring is particularly important
- NSAIDs, salicylates – may enhance the blood sugar-lowering effect; monitor for hypoglycemia
- Corticosteroids (e.g., prednisolone) – may increase blood sugar levels and reduce the effectiveness of Enyglid; dose adjustment may be needed
- Thiazide diuretics – may increase blood sugar levels; monitoring recommended
- Oral contraceptives – may affect blood sugar control; discuss with your doctor
- Phenytoin, carbamazepine (CYP3A4 inducers) – may reduce repaglinide blood levels; diabetes control may need reassessment
Alcohol can enhance the blood sugar-lowering effect of Enyglid and increase the risk of hypoglycemia. Additionally, alcohol can impair your ability to recognise the warning signs of low blood sugar. If you drink alcohol, do so in moderation and never on an empty stomach. Discuss alcohol consumption with your doctor.
What Is the Correct Dosage of Enyglid?
The usual starting dose of Enyglid is 0.5 mg taken before each main meal. The dose can be increased by your doctor up to a maximum of 4 mg per meal, with a maximum daily dose of 16 mg. It should be taken immediately before or up to 30 minutes before eating.
Enyglid dosing is unique compared to many other oral diabetes medicines because it follows a meal-based dosing schedule rather than a fixed once- or twice-daily regimen. This means the number of doses per day varies depending on how many main meals you eat. If you eat three main meals a day, you take three doses; if you skip a meal, you skip the corresponding dose. This flexibility is one of the key advantages of repaglinide over sulphonylureas.
Adults
| Patient Group | Starting Dose | Maintenance Dose | Maximum Dose |
|---|---|---|---|
| Treatment-naive patients | 0.5 mg before each main meal | 0.5–4 mg before each meal | 4 mg per meal, 16 mg/day |
| Switching from another oral antidiabetic | 1 mg before each main meal | 0.5–4 mg before each meal | 4 mg per meal, 16 mg/day |
| Combination with metformin | 0.5 mg before each main meal | Adjusted based on blood glucose | 4 mg per meal, 16 mg/day |
| Hepatic impairment (mild–moderate) | 0.5 mg with careful titration | Use lowest effective dose | Individualised – longer titration intervals |
Dose adjustments are typically made at intervals of 1 to 2 weeks, based on blood glucose monitoring results. Your doctor may use fasting blood glucose levels and HbA1c measurements to determine the appropriate dose for you. The goal is to achieve the lowest effective dose that controls your blood sugar without causing hypoglycemia.
Children
Enyglid is not recommended for use in children and adolescents under 18 years of age. There are no adequate clinical data on the safety and efficacy of repaglinide in paediatric patients. Type 2 diabetes in children is typically managed with lifestyle modifications and, if necessary, metformin or insulin therapy.
Elderly
Clinical studies of repaglinide have included patients up to 75 years of age, and no overall differences in efficacy or safety have been observed compared with younger adults. However, greater sensitivity in some older individuals cannot be ruled out. Elderly patients may be more susceptible to hypoglycemia, particularly if they have irregular eating patterns, reduced renal function, or are taking multiple medicines. Dose initiation and titration should be performed with particular caution, starting with the lowest available dose of 0.5 mg.
Missed Dose
If you forget to take your dose before a meal and you have already started eating or the meal has passed, skip the missed dose. Do not take a double dose to compensate. Simply take your usual dose before the next meal. Since Enyglid works specifically around mealtimes, taking it between meals or after a meal has no benefit and may increase the risk of hypoglycemia at an inappropriate time.
Overdose
An overdose of Enyglid may cause severe hypoglycemia, which can manifest as sweating, tremor, hunger, confusion, seizures, and loss of consciousness. If you suspect an overdose:
- If the patient is conscious, give fast-acting carbohydrates immediately (glucose tablets, fruit juice, sugary drink)
- If the patient is unconscious, call emergency services immediately and place the patient in the recovery position
- Glucagon injection may be administered if available
- Intravenous glucose may be required in a hospital setting
- Continue monitoring blood glucose for at least 24 hours after a significant overdose, as hypoglycemia may recur
If someone taking Enyglid loses consciousness or has seizures, this is a medical emergency. Call your local emergency number immediately. Do not attempt to give food or drink to an unconscious person. If glucagon is available and you have been trained to use it, administer it as directed while waiting for emergency services.
What Are the Side Effects of Enyglid?
The most common side effect of Enyglid is hypoglycemia (low blood sugar). Other side effects include gastrointestinal disturbances such as abdominal pain, diarrhea, nausea, and constipation. Allergic skin reactions and visual disturbances may occur rarely.
Like all medicines, Enyglid can cause side effects, although not everyone experiences them. The frequency and severity of side effects often depend on the dose, individual patient factors, and concurrent medicines. Most side effects of repaglinide are related to its primary pharmacological action of lowering blood sugar. Understanding these side effects and knowing when to seek medical attention is essential for safe use.
Side effects are classified according to the following frequency convention used by the European Medicines Agency: very common (affects more than 1 in 10 people), common (affects 1 in 10 to 1 in 100 people), uncommon (affects 1 in 100 to 1 in 1,000 people), and rare (affects fewer than 1 in 1,000 people).
Very Common (affects more than 1 in 10)
- Hypoglycemia (low blood sugar) – symptoms include sweating, tremor, hunger, confusion, palpitations, and dizziness
Common (affects 1 in 10 to 1 in 100)
- Abdominal pain
- Diarrhea
- Nausea
- Constipation
- Vomiting
Uncommon (affects 1 in 100 to 1 in 1,000)
- Visual disturbances (usually temporary and related to blood sugar fluctuations)
- Elevated liver enzymes
Rare (affects fewer than 1 in 1,000)
- Allergic skin reactions (rash, itching, urticaria)
- Severe hypersensitivity reactions (anaphylaxis)
- Severe liver dysfunction (jaundice, abnormal liver function tests)
- Stevens-Johnson syndrome (very rare, serious skin condition)
Managing hypoglycemia
Since hypoglycemia is the most common side effect of Enyglid, it is important to recognise and manage it effectively. Mild to moderate hypoglycemia can usually be self-treated by consuming fast-acting carbohydrates. The following steps are recommended:
- Recognise the symptoms: Cold sweat, cool pale skin, headache, rapid heartbeat, nausea, feeling very hungry, temporary visual changes, drowsiness, tiredness, weakness, nervousness, tremor, anxiety, confusion, and difficulty concentrating
- Act immediately: Consume 15–20 grams of fast-acting glucose (3–4 glucose tablets, 150 ml of fruit juice, or 4–5 sugar cubes)
- Wait 15 minutes: Re-check blood sugar. If still low, repeat the glucose intake
- Follow with a snack: Once blood sugar normalises, eat a small snack containing complex carbohydrates (e.g., bread or crackers) to prevent recurrence
Contact your doctor if you experience frequent hypoglycemic episodes (more than once or twice per week), persistent gastrointestinal symptoms, any signs of an allergic reaction (skin rash, swelling, difficulty breathing), or yellowing of the skin or eyes (jaundice). Your doctor may need to adjust your dose or consider alternative treatment.
How Should You Store Enyglid?
Store Enyglid tablets in their original packaging at room temperature below 25°C. Keep away from moisture, heat, and direct sunlight. Do not use after the expiry date printed on the packaging.
Proper storage of Enyglid ensures the medicine remains effective and safe throughout its shelf life. Incorrect storage conditions can cause the active ingredient to degrade, potentially reducing its effectiveness or producing harmful breakdown products.
Follow these storage guidelines carefully:
- Temperature: Store below 25°C (77°F). Do not freeze
- Original packaging: Keep the tablets in their original blister pack to protect from moisture and light
- Moisture: Do not store in bathrooms or other humid environments
- Sunlight: Avoid direct sunlight exposure
- Children: Keep out of sight and reach of children
- Expiry date: Check the expiry date on the packaging. Do not use Enyglid after this date
- Disposal: Do not dispose of unused medicines via household waste or wastewater. Return unused tablets to your pharmacy for safe disposal
If you notice any change in the appearance of the tablets (discolouration, crumbling, unusual odour), do not take them and return them to your pharmacy. Enyglid 0.5 mg tablets are normally white, round, and biconvex with bevelled edges.
What Does Enyglid Contain?
Each Enyglid 0.5 mg tablet contains 0.5 mg of the active substance repaglinide, along with inactive excipients including microcrystalline cellulose, calcium hydrogen phosphate, maize starch, polacrilin potassium, povidone, glycerol, meglumine, poloxamer, and magnesium stearate.
Understanding the composition of your medicine is important, particularly if you have known allergies or intolerances to specific ingredients. The active ingredient is the component responsible for the therapeutic effect, while the excipients (inactive ingredients) serve various functions such as binding, filling, and ensuring proper tablet disintegration and absorption.
Active ingredient
Repaglinide 0.5 mg – This is the active pharmaceutical ingredient (API) that produces the blood glucose-lowering effect. Repaglinide is a carbamoylmethyl benzoic acid derivative belonging to the meglitinide pharmacological class. It has the molecular formula C27H36N2O4 and a molecular weight of approximately 452.6 g/mol.
Excipients (inactive ingredients)
- Microcrystalline cellulose – Filler and binder that gives the tablet its structural integrity
- Calcium hydrogen phosphate (anhydrous) – Diluent and stabiliser
- Maize starch – Disintegrant that helps the tablet break down in the stomach
- Polacrilin potassium – Superdisintegrant to promote rapid tablet disintegration
- Povidone (K25) – Binder used during the granulation process
- Glycerol (85%) – Plasticiser and humectant
- Meglumine – pH adjuster and stabiliser
- Poloxamer – Surfactant to improve wettability and dissolution
- Magnesium stearate – Lubricant to prevent the tablet from sticking to manufacturing equipment
Enyglid 0.5 mg tablets do not contain lactose, gluten, sucrose, or any animal-derived ingredients. However, if you have a known allergy to any of the listed excipients, inform your doctor or pharmacist before starting treatment. The tablets contain maize starch, which is generally well-tolerated even by individuals with coeliac disease, as the starch processing removes gluten proteins.
Tablet description
The 0.5 mg tablets are white, round, and biconvex with bevelled edges. Enyglid is also available in 1 mg tablets (yellow) and 2 mg tablets (peach/salmon-coloured), each containing the same excipients with the addition of iron oxide yellow (E172) and/or iron oxide red (E172) as colouring agents in the higher-strength formulations.
Frequently Asked Questions About Enyglid
Enyglid (repaglinide) is used to treat type 2 diabetes mellitus in adults when blood sugar levels cannot be adequately controlled by diet, exercise, and weight reduction alone. It works by stimulating the pancreas to release more insulin, particularly around mealtimes. It can be used as monotherapy or in combination with metformin for improved blood sugar control.
Take Enyglid orally, immediately before or up to 30 minutes before each main meal. Swallow the tablet with a glass of water. The usual starting dose is 0.5 mg before each meal. Your doctor may adjust the dose up to a maximum of 4 mg per meal (16 mg per day). If you skip a meal, skip the corresponding dose of Enyglid. Never take a double dose.
The most common side effect is hypoglycemia (low blood sugar), which can cause symptoms such as cold sweat, pale skin, headache, rapid heartbeat, nausea, hunger, drowsiness, tremor, and confusion. Other common side effects include abdominal pain, diarrhea, nausea, constipation, and vomiting. Most gastrointestinal side effects are mild and temporary. Always carry glucose tablets or a sugary drink in case of low blood sugar.
Enyglid can be combined with metformin when blood sugar is not adequately controlled on either medicine alone. However, it must NOT be taken with gemfibrozil (a cholesterol-lowering medicine) as this dramatically increases repaglinide blood levels and hypoglycemia risk. Discuss all your current medicines with your doctor before starting Enyglid, including over-the-counter medicines and herbal supplements.
No, Enyglid should not be used during pregnancy or breastfeeding. There are no adequate studies in pregnant women, and animal studies have shown potential harm. If you are planning a pregnancy or become pregnant while taking Enyglid, stop the medicine and contact your doctor immediately. Insulin is the recommended treatment for managing diabetes during pregnancy.
If you experience mild symptoms of low blood sugar (sweating, trembling, hunger, confusion), immediately consume 15–20 grams of fast-acting sugar such as glucose tablets, fruit juice, or sugary sweets. Wait 15 minutes and re-check your blood sugar. If still low, repeat the sugar intake. If symptoms are severe or you or someone else loses consciousness, call emergency services immediately. Always carry glucose tablets with you.
References
This article is based on the following peer-reviewed sources and international guidelines:
- European Medicines Agency (EMA). Enyglid – Summary of Product Characteristics. European Public Assessment Report (EPAR). Available at: EMA Enyglid EPAR.
- American Diabetes Association (ADA). Standards of Medical Care in Diabetes – 2025. Diabetes Care. 2025;48(Suppl. 1):S1–S326. DOI: 10.2337/dc25-SINT.
- Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2022;65(12):1925–1966.
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List, 2023. Geneva: WHO; 2023.
- British National Formulary (BNF). Repaglinide. NICE Evidence Services. Available at: bnf.nice.org.uk.
- Hatorp V, Hansen KT, Thomsen MS. Influence of drugs interacting with CYP3A4 on the pharmacokinetics, pharmacodynamics, and safety of the prandial glucose regulator repaglinide. Journal of Clinical Pharmacology. 2003;43(6):649–660.
- Niemi M, Backman JT, Neuvonen M, Neuvonen PJ. Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics and pharmacodynamics of repaglinide: potentially hazardous interaction between gemfibrozil and repaglinide. Diabetologia. 2003;46(3):347–351.
- Food and Drug Administration (FDA). Prandin (repaglinide) Tablets – Prescribing Information. U.S. FDA; 2019.
- Mayo Clinic. Repaglinide (Oral Route) – Description and Brand Names. Mayo Clinic Patient Education. 2025.
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