Medically reviewed by Drugs.com. Last updated on Aug 18, 2020.
(GLYE me pye ride)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Amaryl: 1 mg [scored]
Amaryl: 2 mg, 4 mg [scored; contains fd&c blue #2 aluminum lake]
Generic: 1 mg, 2 mg, 4 mg
Brand Names: U.S.
- Antidiabetic Agent, Sulfonylurea
Stimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites
Vd: 8.8 L
Hepatic oxidation via CYP2C9 to M1 metabolite (~33% activity of parent compound); further oxidative metabolism to inactive M2 metabolite
Urine (60%, 80% to 90% as M1 and M2 metabolites); feces (40%, 70% as M1 and M2 metabolites)
Onset of Action
Peak effect: Blood glucose reductions: 2 to 3 hours
Time to Peak
2 to 3 hours
Duration of Action
5 to 9 hours
Special Populations: Renal Function Impairment
As renal function declines, glimepiride serum levels decrease and metabolite (M1 and M2) AUC and half-lives increase. Patients with CrCl <20 mL/minute had 2.3-fold higher AUC of M1 (an active metabolite) compared to patients with CrCl >50 mL/minute.
Use: Labeled Indications
Diabetes mellitus, type 2, treatment: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Hypersensitivity to glimepiride, any component of the formulation, or sulfonamides
Note: Although the FDA approved product labeling states this medication is contraindicated with other sulfonamide-containing drug classes, the scientific basis of this statement has been challenged. See “Warnings/Precautions” for more detail.
Documentation of allergenic cross-reactivity for drugs in this class is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Canadian labeling: Additional contraindications (not in US labeling): Pregnancy; breastfeeding; type 1 diabetes; diabetic ketoacidosis (with or without coma); severe renal or hepatic impairment
Diabetes mellitus, type 2, treatment:
Note: Adjunctive therapy or alternative monotherapy for patients who have suboptimal response to or cannot take metformin. Sulfonylureas are associated with a greater risk of hypoglycemia than other noninsulin antidiabetic agents (AACE [Garber 2020]; ADA 2020); if one is chosen, a sulfonylurea with a lower relative risk of hypoglycemia (eg, glimepiride) is preferred (ADA 2020; ADA/EASD [Davies 2018]).
Initial: 1 to 2 mg once daily, administered with breakfast or the first main meal.
Titration: If adequate glycemic control is not obtained, may increase dose in 1 to 2 mg increments no more frequently than every 1 to 2 weeks.
Maximum: 8 mg/day. Note: Increasing dosage from 4 to 8 mg/day may only provide modest glycemic benefit (Goldberg 1996). The 8 mg/day dosage may be administered in 1 or 2 divided doses (Rosenstock 1996).
Patients already maintained on glimepiride who require hospitalization: In patients who require hospitalization, consider temporary discontinuation of noninsulin antidiabetic agents (Bogun 2013; Inzucchi 2006) and initiation and/or continuation of insulin therapy (ADA 2020; Bogun 2013; Inzucchi 2006). Use of noninsulin antidiabetic agents may be considered in noncritically ill hospitalized patients if there are no contraindications, nutrition is consistent, and blood glucose is well controlled; close monitoring and subsequent dosage adjustments are recommended (Bogun 2013; Inzucchi 2006).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Associated with hypoglycemia; the American Geriatrics Society recommends avoiding glimepiride, whereas the American Diabetes Association suggests using with caution as glimepiride has a lower relative risk of hypoglycemia than other sulfonylureas (ADA 2020; Beers Criteria [AGS 2019]). In cases where glimepiride is used, initiate at 1 mg once daily and monitor closely (Wexler 2020).
Oral: Administer once daily with breakfast or first main meal of the day. Patients that are NPO or require decreased caloric intake may need doses held to avoid hypoglycemia.
Take with breakfast or the first main meal of the day. Individualized medical nutrition therapy based on American Diabetes Association recommendations is an integral part of therapy.
Store at 25°C (77°F); excursions permitted between 20°C and 25°C (68°F and 77°F)
Ajmaline: Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Monitor therapy
Alcohol (Ethyl): Sulfonylureas may enhance the adverse/toxic effect of Alcohol (Ethyl). A flushing reaction may occur. Monitor therapy
Alpelisib: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Monitor therapy
Alpha-Glucosidase Inhibitors: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with an alpha-glucosidase inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Avoid combination
Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Monitor therapy
Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Exceptions: Danazol. Monitor therapy
Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Beta-Blockers: May enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. Exceptions: Levobunolol; Metipranolol. Monitor therapy
Carbocisteine: Sulfonylureas may enhance the adverse/toxic effect of Carbocisteine. Specifically, sulfonylureas may enhance adverse effects of alcohol that is present in liquid formulations of carbocisteine-containing products. Monitor therapy
Chloramphenicol (Systemic): May increase the serum concentration of Sulfonylureas. Monitor therapy
Cimetidine: May increase the serum concentration of Sulfonylureas. Monitor therapy
Colesevelam: May decrease the serum concentration of Glimepiride. Management: Administer glimepiride at least 4 hours prior to colesevelam. Consider therapy modification
Cyclic Antidepressants: May enhance the hypoglycemic effect of Sulfonylureas. Monitor therapy
CYP2C9 Inducers (Moderate): May decrease the serum concentration of Sulfonylureas. Monitor therapy
CYP2C9 Inhibitors (Moderate): May increase the serum concentration of Sulfonylureas. Monitor therapy
Dexketoprofen: May enhance the adverse/toxic effect of Sulfonamides. Monitor therapy
Dipeptidyl Peptidase-IV Inhibitors: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Elexacaftor, Tezacaftor, and Ivacaftor: May increase the serum concentration of Glimepiride. Monitor therapy
Fibric Acid Derivatives: May enhance the hypoglycemic effect of Sulfonylureas. Monitor therapy
Glucagon-Like Peptide-1 Agonists: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose reductions when used in combination with glucagon-like peptide-1 agonists. Consider therapy modification
Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy
Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Lumacaftor and Ivacaftor: May decrease the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor and Ivacaftor may increase the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Monitor therapy
Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Mecamylamine: Sulfonamides may enhance the adverse/toxic effect of Mecamylamine. Avoid combination
Metreleptin: May enhance the hypoglycemic effect of Sulfonylureas. Management: Sulfonylurea dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely. Consider therapy modification
Miconazole (Oral): May enhance the hypoglycemic effect of Sulfonylureas. Miconazole (Oral) may increase the serum concentration of Sulfonylureas. Monitor therapy
Mitiglinide: May enhance the adverse/toxic effect of Sulfonylureas. Avoid combination
Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy
Probenecid: May decrease the protein binding of Sulfonylureas. Probenecid may increase the serum concentration of Sulfonylureas. Monitor therapy
Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy
RaNITIdine (Withdrawn from US Market): May increase the serum concentration of Sulfonylureas. Monitor therapy
Rifapentine: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Monitor therapy
Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Monitor therapy
Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Sulfonamide Antibiotics: May enhance the hypoglycemic effect of Sulfonylureas. Monitor therapy
Tezacaftor and Ivacaftor: May increase the serum concentration of Glimepiride. Monitor therapy
Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Thiazolidinediones: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose adjustments in patients taking thiazolidinediones and monitor for hypoglycemia. Consider therapy modification
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy
Vitamin K Antagonists (eg, warfarin): Sulfonylureas may enhance the anticoagulant effect of Vitamin K Antagonists. Vitamin K Antagonists may enhance the hypoglycemic effect of Sulfonylureas. Monitor therapy
Voriconazole: May increase the serum concentration of Sulfonylureas. Monitor therapy
>10%: Endocrine & metabolic: Hypoglycemia (4% to 20%)
1% to 10%:
Central nervous system: Dizziness (2%), headache
Gastrointestinal: Nausea (5%)
Hepatic: Increased serum ALT (2%)
Respiratory: Flu-like symptoms (5%)
Miscellaneous: Accidental injury (6%)
<1%, postmarketing, and/or case reports: Abnormal hepatic function tests, accommodation disturbance (early treatment), agranulocytosis, alopecia, anaphylaxis, angioedema, aplastic anemia, cholestatic jaundice, diarrhea, disulfiram-like reaction, dysgeusia, dyspnea, erythema, gastrointestinal pain, hemolytic anemia, hepatic failure, hepatic insufficiency, hepatic porphyria, hepatitis, hypersensitivity, hypersensitivity angiitis, hyponatremia, hypotension, immune thrombocytopenia, leukopenia, maculopapular rash, morbilliform rash, pancytopenia, porphyria cutanea tarda, pruritus, shock, SIADH, skin photosensitivity, Stevens-Johnson syndrome, thrombocytopenia, urticaria, vomiting, weight gain
Concerns related to adverse effects:
• Cardiovascular mortality: Product labeling states oral hypoglycemic drugs may be associated with an increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. Data to support this association are limited, and several studies, including a large prospective trial (UKPDS 1998), have not supported an association. In a prospective, active-controlled study comparing linagliptin to glimepiride in patients with high baseline cardiovascular risk, the rates of cardiovascular events were similar over ~6 years (Rosenstock 2019). In patients with established atherosclerotic cardiovascular disease, other agents (eg, with demonstrated cardiovascular risk reduction) are preferred (ADA 2020).
• Hypoglycemia: All sulfonylurea drugs are capable of producing severe hypoglycemia. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when ethanol is ingested, or when more than one glucose-lowering drug is used. It is also more likely in elderly patients, malnourished patients, and in patients with impaired renal or hepatic function; use with caution.
• Sulfonamide (“sulfa”) allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or, at the very least, this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.
• Bariatric surgery:
– Altered absorption: Use IR formulations after surgery to minimize the potential effects of bypassing stomach and proximal small bowel with gastric bypass or more rapid gastric emptying and proximal small bowel transit with sleeve gastrectomy (Apovian 2015). ER formulations may have altered release and absorption patterns after gastric bypass or sleeve gastrectomy (but not gastric band). Compared to control, Tmax in a gastric bypass cohort administered tolbutamide was significantly shorter (1.4 ± 1.8 vs 5.1 ± 1.7 hours; P < 0.001), while Cmax and AUC0-∞ were not altered (Tandra 2013).
– Hypoglycemia: Use an antidiabetic agent without the potential for hypoglycemia if possible; hypoglycemia may occur after gastric bypass, sleeve gastrectomy, and gastric band (Mechanick 2013). Insulin secretion and sensitivity may be partially or completely restored after these procedures (gastric bypass is most effective, followed by sleeve, and finally band) (Korner 2009; Peterli 2012). First-phase insulin secretion and hepatic insulin sensitivity have been shown to be significantly improved in the immediate days after gastric bypass and sleeve gastrectomy. The restorative effects of these procedures on peripheral insulin sensitivity may occur later in the 3- to 12-month period postsurgery (Mingrone 2016).
– Weight gain: Evaluate risk vs benefit and consider alternative therapy after gastric bypass, sleeve gastrectomy, and gastric banding; weight gain may occur (Apovian 2015).
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency: Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency may be at an increased risk of sulfonylurea-induced hemolytic anemia; however, cases have also been described in patients without G6PD deficiency during postmarketing surveillance. Use with caution and consider a nonsulfonylurea alternative in patients with G6PD deficiency.
• Hepatic impairment: Use with caution; patients with hepatic impairment are more likely to develop hypoglycemia.
• Renal impairment: Use with caution and reduce dosage; patients with renal impairment are more likely to develop hypoglycemia.
• Stress-related states: It may be necessary to discontinue therapy and administer insulin if the patient is exposed to stress (eg, fever, trauma, infection, surgery).
• CYP2C9 genotype: Systemic exposure of glimepiride is increased in patients with CYP2C9*3 allele (Niemi 2002).
• Elderly: Use with caution; elderly patients are more likely to develop hypoglycemia.
• Appropriate use: Not indicated for use in patients with type 1 diabetes mellitus or with diabetic ketoacidosis.
Monitor for signs and symptoms of hypoglycemia (fatigue, excessive hunger, profuse sweating, numbness of extremities), blood glucose, hemoglobin A1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2020]), renal function
Information related to the use of glimepiride during pregnancy is limited (Balaguer Santamaría 2000; Kalyoncu 2005). Severe hypoglycemia lasting 4 to 10 days has been noted in infants born to mothers taking a sulfonylurea at the time of delivery. If exposure during pregnancy occurs, discontinue at least 2 weeks prior to delivery.
Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major birth defects, stillbirth, and macrosomia. To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2020; Blumer 2013).
Agents other than glimepiride are currently recommended to treat diabetes mellitus in pregnancy (ADA 2020).
What is this drug used for?
• It is used to lower blood sugar in patients with high blood sugar (diabetes).
All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
• Flu-like symptoms
• Weight gain
WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating.
• Severe dizziness
• Passing out
• Shortness of breath
• Severe loss of strength and energy
• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes.
• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
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- Drug class: sulfonylureas
Other brands: Amaryl