Meglitinide – short-acting oral insulin secretagogue
Brand names: NovoNorm, Prandin, Repaglinida Cinfa
Updated · Methodology
Second line
Second-line in T2D per / 2024 and SED 2023. Used in patients with irregular meals or intolerance to metformin or sulfonylureas. Dose 0.5–4 mg before each meal. Particularly useful in CKD – no accumulation with reduced eGFR (advantage over sulfonylureas). Skip the dose if a meal is skipped – lower hypoglycemia risk.
Sources
ICD-10: E11 · ICD-11: 5A11
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Repaglinide is a meglitinide, a short-acting antidiabetic that stimulates insulin secretion. It is prescribed for type 2 diabetes (AEMPS Ficha Técnica). In people without diabetes, repaglinide is not used for weight loss: the drug causes hypoglycemia (life-threatening in people with normal blood sugar) and weight gain (paradoxically, via insulin stimulation). If repaglinide was prescribed for weight loss without diabetes, seek a second opinion immediately.
A benzoic acid derivative. Blocks ATP-dependent potassium channels in pancreatic β-cells, causing membrane depolarization, calcium channel opening, and insulin release. Binds a different sulfonylurea receptor site than sulfonylureas – rapid and short action. CYP3A4 and CYP2C8 metabolism. Half-life 1 hour – lower hypoglycemia risk than long-acting sulfonylureas.
In pregnant T2D patients, insulin is base therapy; oral antidiabetics are usually discontinued.
Not used during lactation.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
1 pair found. Sorted from critical to minor.
Mechanism
Repaglinide is metabolised by CYP2C8 and taken up by the liver through OATP1B1. Gemfibrozil blocks both routes at once and repaglinide clearance falls. In healthy volunteers, gemfibrozil 600 mg twice daily for 3 days raised repaglinide AUC 8.1-fold and the plasma concentration 7 hours post-dose 28.6-fold.
Symptoms
Severe hypoglycemia: cold sweat, tremor, confusion, seizures, loss of consciousness. The episode arrives later than usual and lasts longer, because repaglinide is cleared many times more slowly. Nocturnal hypoglycemia carries the greatest danger: the person does not wake at the first signs.
Management
The label prohibits this combination, and no dose-reduction workaround exists. If both drugs are already prescribed, repaglinide is switched to an agent with a different metabolic route rather than dose-reduced. During the switch, blood glucose is self-monitored frequently for the first days: CYP2C8 inhibition by the gemfibrozil glucuronide is irreversible and resolves as the enzyme is replaced, not within hours.
Sources
Verbatim lines from the interaction sections, in the language of the label
«Uso concomitante de gemfibrozilo (ver sección 4.5).»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: Concomitant use of gemfibrozil [see Drug Interactions (7) ]»FDA, section 4 · Open on DailyMed
«En un ensayo realizado en voluntarios sanos, la administración concomitante de repaglinida (en una única dosis de 0,25 mg) y de ciclosporina (dosis repetidas de 100 mg), aumentó el AUC y la Cmáx de…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Intervention: Avoid concomitant use of repaglinide with clopidogrel. If concomitant use cannot be avoided, initiate repaglinide at 0.5 mg before each meal and do not exceed a total…»FDA, section 7 · Open on DailyMed
«En un ensayo de interacción realizado con voluntarios sanos, la coadministración de deferasirox (30 mg/AEMPS, section 4.5 · Open on CIMA
«La co-administración de trimetoprim (160 mg dos veces al día), un inhibidor moderado de CYP2C8 y repaglinida (una dosis única de 0,25 mg) aumentó el valor AUC de repaglinida, Cmax y t1/AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: CYP2C8 and CYP3A4 Inducers and Drugs That May Decrease the Blood Glucose Lowering Effect of Repaglinide : Co-administration may require repaglinide dose increases and increased…»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: CYP2C8 and CYP3A4 Inhibitors and Drugs That May Increase the Risk of Hypoglycemia : Co-administration may require repaglinide dose reductions and increased frequency of glucose…»FDA, section 7 · Open on DailyMed
«El uso concomitante de rifampicina y repaglinida puede por lo tanto, necesitar el ajuste de la dosis de repaglinida, en base a una cuidadosa monitorización de las concentraciones de glucosa en…»AEMPS, section 4.5 · Open on CIMA
«El uso concomitante de rifampicina y repaglinida puede por lo tanto, necesitar el ajuste de la dosis de repaglinida, en base a una cuidadosa monitorización de las concentraciones de glucosa en…»AEMPS, section 4.5 · Open on CIMA
«El uso concomitante de rifampicina y repaglinida puede por lo tanto, necesitar el ajuste de la dosis de repaglinida, en base a una cuidadosa monitorización de las concentraciones de glucosa en…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Examples: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, nonsteroidal…»FDA, section 7 · Open on DailyMed
«Las siguientes sustancias pueden potenciar y/AEMPS, section 4.5 · Open on CIMA
«Las siguientes sustancias pueden reducir el efecto hipoglucemiante de la repaglinida: anticonceptivos orales, rifampicina, barbitúricos, carbamacepina, tiazidas, corticosteroides, danazol, hormonas…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Examples: Atypical antipsychotics (e.g., olanzapine and clozapine), calcium channel antagonists, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral…»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Examples: Drugs that induce the CYP3A4 and/FDA, section 7 · Open on DailyMed
«Las siguientes sustancias pueden reducir el efecto hipoglucemiante de la repaglinida: anticonceptivos orales, rifampicina, barbitúricos, carbamacepina, tiazidas, corticosteroides, danazol, hormonas…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Examples: beta-blockers, clonidine, guanethidine, and reserpine»FDA, section 7 · Open on DailyMed
«Las siguientes sustancias pueden potenciar y/AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Examples: Drugs that are known to inhibit CYP3A4 include antifungal agents (ketoconazole, itraconazole) and antibacterial agents (clarithromycin, erythromycin). Drugs that are…»FDA, section 7 · Open on DailyMed
«DRUG INTERACTIONS: Examples: beta-blockers, clonidine, guanethidine, and reserpine»FDA, section 7 · Open on DailyMed
«Las siguientes sustancias pueden potenciar y/AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Examples: Atypical antipsychotics (e.g., olanzapine and clozapine), calcium channel antagonists, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral…»FDA, section 7 · Open on DailyMed
«Las siguientes sustancias pueden reducir el efecto hipoglucemiante de la repaglinida: anticonceptivos orales, rifampicina, barbitúricos, carbamacepina, tiazidas, corticosteroides, danazol, hormonas…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Examples: Atypical antipsychotics (e.g., olanzapine and clozapine), calcium channel antagonists, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral…»FDA, section 7 · Open on DailyMed
«Uso concomitante de repaglinida, dasabuvir, selexipag (ver sección 4.5) simvastatina o rosuvastatina 40 mg (ver secciones 4.4 y 4.5).»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: Combination therapy of gemfibrozil with repaglinide (see PRECAUTIONS ).»FDA, section 4 · Open on DailyMed
«Interacción con repaglinida y otros medicamentos que se metabolizan por CYP2C8: En un estudio con voluntarios sanos, la administración concomitante de deferasirox como inhibidor moderado de CYP2C8…»AEMPS, section 4.5 · Open on CIMA
«Posibilidad de que afecte a la exposición de otros medicamentos: En un estudio de interacción CYP2C8 fármaco-fármaco en sujetos sanos, el AUC de pioglitazona aumentó un 46% y los AUCs de M-III y…»AEMPS, section 4.5 · Open on CIMA
«Antidiabéticos orales/AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Nateglinide Pioglitazone Repaglinide Rosiglitazone Use With Caution Nateglinide, Pioglitazone, Repaglinide, Rosiglitazone: [See Warnings and Precautions (5.4) and Adverse Reactions…»FDA, section 7 · Open on DailyMed
«Medicamentos sustratos del CYP2C8: Clopidogrel ha mostrado un incremento a la exposición de repaglinida en voluntarios sanos. Estudios in vitro han mostrado un incremento en la exposición de…»AEMPS, section 4.5 · Open on CIMA
«Repaglinide (CYP2C8 Substrates): The acyl-β-glucuronide metabolite of clopidogrel is a strong inhibitor of CYP2C8. Clopidogrel can increase the systemic exposure to drugs that are primarily cleared…»FDA, section 7 · Open on DailyMed
«Transporters: Use caution when concomitantly administering eltrombopag and drugs that are substrates of OATP1B1 (e.g., atorvastatin, bosentan, ezetimibe, fluvastatin, glyburide, olmesartan…»FDA, section 7 · Open on DailyMed
«Dosis repetidas de A771726 aumentaron la C max media y la AUC (1,7- y 2,4-veces, respectivamente) de la repaglinida, sugiriendo que el A771726 es un inhibidor de CYP2C8 in vivo. Por tanto, se…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Teriflunomide is an inhibitor of CYP2C8 in vivo . In patients taking leflunomide, exposure of drugs metabolized by CYP2C8 (e.g., paclitaxel, pioglitazone, repaglinide…»FDA, section 7 · Open on DailyMed
«CYP2C8 and CYP3A Substrates: Spironolactone is an irreversible inhibitor for CYP2C8 and CYP3A4/FDA, section 7 · Open on DailyMed
«Potential for Atazanavir to Affect Other Drugs: Atazanavir is an inhibitor of CYP3A and UGT1A1. Coadministration of atazanavir and drugs primarily metabolized by CYP3A or UGT1A1 may result in…»FDA, section 7 · Open on DailyMed
«Número de veces que cambia la exposición con ciclosporina: Ciclosporina puede incrementar las concentraciones plasmáticas de repaglinida y por lo tanto, incrementar el riesgo de hipoglucemia.»AEMPS, section 4.5 · Open on CIMA
«Medicamentos que pueden estar afectados por darunavir potenciado con ritonavir: Aunque el efecto sobre CYP2C8 sólo haya sido estudiado in vitro , la administración conjunta de darunavir y ritonavir…»AEMPS, section 4.5 · Open on CIMA
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Repaglinide is evaluated for the following indications with varying evidence strength: Type 2 diabetes mellitus (evidence tier B), Weight loss (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Repaglinide (≥ 1 in 100): Hypoglycemia, Weight gain, Nausea, Abdominal pain, Diarrhea. See the Safety section for uncommon and serious reactions.
In pregnant T2D patients, insulin is base therapy; oral antidiabetics are usually discontinued.
Not used during lactation.
Repaglinide is contraindicated in: Repaglinide hypersensitivity; Type 1 diabetes; Diabetic ketoacidosis; Severe hepatic impairment; Concomitant gemfibrozil or itraconazole. Full list in the Safety section.
Direct links to regulator labels. Open in a new tab.
Semaglutide, Sitagliptin, Sitagliptin + Metformin, Tirzepatide, Glibenclamide, Insulin degludec, Insulin lispro, Vildagliptin