Note: The 30 mg modified-release tablet is equivalent to the 80 mg immediate-release tablet.
Diabetes mellitus, type 2, treatment:
Note: May be used as an adjunctive agent or alternative monotherapy for patients in whom initial therapy with lifestyle modification and metformin failed or who cannot take metformin. Sulfonylureas are associated with a greater risk of hypoglycemia than other noninsulin antidiabetic agents; if one is chosen, a sulfonylurea with a lower relative risk of hypoglycemia (eg, gliclazide, glipizide, glimepiride) is preferred (AACE [Garber 2020]; ADA 2021; ADA/EASD [Davies 2018]).
Immediate-release tablet:
Oral: Initial: 40 to 80 mg once daily with the first main meal (Wexler 2021).
Dosage adjustment: May increase dose in 40 to 80 mg increments every 1 to 4 weeks if needed to achieve glycemic goals; usual maintenance dose: 40 to 160 mg/day (maximum: 320 mg/day) (DeFronzo 1999; Wexler 2021; manufacturer’s labeling). Note: Administer doses ≥160 mg/day in 2 divided doses.
Note: Dosing in the prescribing information may not reflect current clinical practice and is not routinely recommended.
Modified-release tablet:
Oral: Initial: 30 mg once daily with the first main meal.
Dosage adjustment: May increase dose in 30 mg increments every 1 to 4 weeks if needed to achieve glycemic goals; usual maintenance dose: 30 to 60 mg/day (maximum: 120 mg/day) (DeFronzo 1999; Wexler 2021; manufacturer’s labeling).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to moderate impairment:
Immediate-release tablet: Initial: 40 mg once daily (Wexler 2021).
Modified-release tablet: No dosage adjustment required; adjust dose cautiously.
Severe impairment: Use is contraindicated.
Mild to moderate impairment
Immediate-release tablet: There are no specific dosage adjustments provided in the manufacturer’s labeling; however, a dosage reduction may be required.
Modified-release tablet: Refer to adult dosing.
Severe impairment: Use is contraindicated.
Note: Sulfonylureas should be used with caution in elderly patients due to the increased risk of severe hypoglycemia. If a sulfonylurea is chosen, one with a lower potential for hypoglycemia (eg, gliclazide) is preferred (Diabetes Canada 2018).
Immediate-release tablet: Initial: 40 mg once daily (Wexler 2021).
Modified-release tablet: Refer to adult dosing.
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Diamicron: 80 mg [contains corn starch]
Generic: 80 mg
Tablet Extended Release 24 Hour, Oral:
Diamicron MR: 30 mg, 60 mg
Generic: 30 mg, 60 mg
Not available in the US
Oral: Patients that are NPO or require decreased caloric intake may need doses held to avoid hypoglycemia. Administer with meals (modified-release tablet should be administered with breakfast). May split the 60 mg modified-release tablets in half; however, the 30 mg modified-release tablets must be swallowed whole. Modified-release tablets should not be crushed or chewed.
Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Consider switching to immediate-release tablets.
Note: Not approved in the United States.
Diabetes mellitus, type 2, treatment: Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Endocrine & metabolic: Hypoglycemia (11% to 12%)
1% to 10%:
Cardiovascular: Hypertension (3% to 4%), angina pectoris (2%), peripheral edema (1%)
Central nervous system: Headache (4% to 5%), dizziness (2%), depression (1% to 2%), insomnia (1% to 2%), neuralgia (≤1%)
Dermatologic: Dermatological disorders (2%), dermatitis (1% to 2%), skin rash (1%; includes maculopapular rash, morbilliform rash), pruritus (≤1%)
Endocrine & metabolic: Hyperglycemia (2%), hyperlipidemia (≤1%), lipid metabolism disorder (≤1%)
Gastrointestinal: Diarrhea (2% to 3%), constipation (1% to 2%), gastroenteritis (1% to 2%), abdominal pain (1%), gastritis (1%), nausea (≤1%)
Genitourinary: Urinary tract infection (3%)
Infection: Viral infection (6% to 8%)
Neuromuscular & skeletal: Back pain (4% to 5%), arthralgia (3% to 4%), asthenia (2% to 3%), arthropathy (2%), myalgia (2%), arthritis (1% to 2%), tendinopathy (1%)
Ophthalmic: Conjunctivitis (1%)
Otic: Otitis media (≤1%)
Respiratory: Bronchitis (4% to 5%), rhinitis (4% to 5%), pharyngitis (4%), upper respiratory tract infection (3% to 4%), cough (2%), pneumonia (1% to 2%), sinusitis (1% to 2%)
Frequency not defined:
Endocrine & metabolic: Increased lactate dehydrogenase
Renal: Increased serum creatinine
<1%, postmarketing, and/or case reports: Abnormal lacrimation, acute myocardial infarction, acute pancreatitis, agranulocytosis, albuminuria, anal fissure, anemia, angioedema, anxiety, arteritis, asthma, auditory disturbance, balanitis, bone disease (spine malformation), breast neoplasm (female; benign), bullous rash, bursitis, cardiac failure, carpal tunnel syndrome, cataract, cerebrovascular disease, chest pain, cholestatic jaundice, colitis, confusion, conjunctival hemorrhage, coronary artery disease, cystitis, dermal ulcer, diplopia, disulfiram-like reaction, drug reaction with eosinophilia and systemic symptoms, duodenal ulcer, dyspepsia, dyspnea, eczema, epigastric fullness, epistaxis, erythema of skin, erythrocytopenia, esophagitis, fecal incontinence, fever, flatulence, fungal dermatitis, fungal infection, gastroesophageal reflux disease, gastrointestinal neoplasm (benign), glaucoma, glycosuria, gout, hemolytic anemia, hemorrhoids, hepatitis, hepatomegaly, hypercholesterolemia, hyperkeratosis, hypersensitivity angiitis, hypersensitivity reaction, hypertriglyceridemia, hypoglycemic coma, hyponatremia, hypotension, hypothyroidism, impotence, increased appetite, increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, increased serum transaminases, increased thirst, infection, leukopenia, lower extremity pain, malaise, mastitis, melena, menstrual disease, nail disease, nephrolithiasis, nervousness, neuropathy, nocturia, onychomycosis, pain, palpitations, pancytopenia, polyuria, prostatic disease, renal cyst, retinopathy, sialorrhea, skeletal pain, Stevens-Johnson syndrome, tachycardia, thrombocytopenia, thrombophlebitis, tinnitus, toothache, toxic epidermal necrolysis, tracheitis, urticaria, vaginitis, vascular disease (vein disorder), visual disturbance, vitreous disorder, vomiting, weight gain, xeroderma, xerophthalmia, xerostomia
Hypersensitivity to gliclazide, other sulfonylureas or sulfonamides, or any component of the formulation; unstable and/or type 1 diabetes mellitus; diabetic ketoacidosis (with or without coma); severe renal or hepatic impairment; stress conditions (eg, serious infection, trauma, surgery); concurrent use with miconazole (systemic or oromucosal gel); pregnancy; breastfeeding.
Note: Although the 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.
Concerns related to adverse effects:
• Cardiovascular mortality: US product labeling of sulfonylureas 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. The American Diabetes Association (ADA) and Canadian guidelines suggest second generation sulfonylureas (including gliclazide) have a neutral cardiovascular risk profile; however, in patients with established atherosclerotic cardiovascular disease, other agents (eg, with demonstrated cardiovascular risk reduction) are preferred (ADA 2021; Diabetes Canada 2018).
• Hypersensitivity: Serious skin and hypersensitivity reactions including rash, pruritus, urticaria, angioedema, erythema, maculopapular rashes, bullous reactions (such as Stevens-Johnson syndrome [SJS] and toxic epidermal necrolysis [TEN]) and drug rash with eosinophilia and systemic symptoms have been reported.
• Hypoglycemia: All sulfonylurea drugs are capable of producing severe hypoglycemia; the incidence of hypoglycemia is least with gliclazide compared to other sulfonylureas (eg, glimepiride, glyburide) (Diabetes Canada 2018). Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when ethanol is ingested, or when >1 glucose-lowering drug is used. It is also more likely in elderly or debilitated patients, malnourished patients, and in patients with endocrine disorders, severe vascular disease, or impaired renal or hepatic function; use with caution. Autonomic neuropathy, advanced age, and concomitant use of beta-blockers or other sympatholytic agents may impair the patient's ability to recognize the signs and symptoms of hypoglycemia; 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, 2 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 (SJS/TEN), some clinicians choose to avoid exposure to these classes.
Disease-related concerns:
• 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 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 in hepatic impairment (undergoes hepatic metabolism); adjust dose cautiously. Cholestasis, jaundice, and hepatitis have been reported rarely; discontinue use if cholestatic jaundice occurs. Use in severe impairment is contraindicated.
• Renal impairment: Use with caution in renal impairment (primarily excreted in urine); adjust dose cautiously. Use in severe impairment is contraindicated.
• Stress-related states: Use during periods of stress (eg, trauma, infection, surgery) is contraindicated. It may be necessary to discontinue therapy and administer insulin if the patient is exposed to stress conditions.
Dosage forms specific issues:
• Lactose: Some formulations may contain lactose; avoid use in patients with galactose intolerance, glucose-galactose malabsorption, or congenital lactose deficiency.
Other warnings/precautions:
• Patient education: Diabetes self-management education is essential to maximize the effectiveness of therapy.
Substrate of CYP2C9 (major), OATP1B1/1B3 (SLCO1B1/1B3); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Ajmaline: Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy
Alcohol (Ethyl): Sulfonylureas may enhance the adverse/toxic effect of Alcohol (Ethyl). A flushing reaction may occur. Risk C: Monitor therapy
Alpelisib: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Risk C: 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. Risk D: Consider therapy modification
Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination
Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy
Amiodarone: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: 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. Risk C: 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. Risk C: Monitor therapy
Chloramphenicol (Systemic): May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy
Cimetidine: May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy
Clarithromycin: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
Cyclic Antidepressants: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
CYP2C9 Inducers (Moderate): May decrease the serum concentration of Sulfonylureas. Risk C: Monitor therapy
CYP2C9 Inhibitors (Moderate): May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy
Dexketoprofen: May enhance the adverse/toxic effect of Sulfonamides. Risk C: 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. Risk D: Consider therapy modification
Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Fibric Acid Derivatives: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: 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. Risk D: Consider therapy modification
Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Herbal Products with Glucose Lowering Effects: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: 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). Risk C: Monitor therapy
Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Mecamylamine: Sulfonamides may enhance the adverse/toxic effect of Mecamylamine. Risk X: Avoid combination
Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy
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 for signs or symptoms of hypoglycemia. Risk D: Consider therapy modification
Miconazole (Oral): May enhance the hypoglycemic effect of Sulfonylureas. Miconazole (Oral) may increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy
Mitiglinide: May enhance the adverse/toxic effect of Sulfonylureas. Risk X: Avoid combination
Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Omeprazole: May increase the serum concentration of Gliclazide. Risk C: Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Probenecid: May decrease the protein binding of Sulfonylureas. Probenecid may increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy
Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: 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. Risk C: Monitor therapy
Rifapentine: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Risk C: Monitor therapy
Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: 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. Risk D: Consider therapy modification
St John's Wort: May decrease the serum concentration of Gliclazide. Risk C: Monitor therapy
Sulfonamide Antibiotics: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
Tetracyclines: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Thiazolidinediones: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose adjustments in patients taking thiazolidinediones and monitor for hypoglycemia. Risk D: Consider therapy modification
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: 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. Risk C: Monitor therapy
Voriconazole: May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy
Ethanol may cause rare disulfiram reactions. Management: Monitor patients.
Sulfonylureas are not recommended for patients with type 2 diabetes mellitus planning to become pregnant. Patients who could become pregnant should use effective contraception during therapy. Transition to a preferred therapy should be initiated prior to conception and contraception should be continued until glycemic control is achieved (ADA 2021; Alexopoulos 2019; Egan 2020)
Gliclazide is contraindicated for use during pregnancy.
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 malformations, stillbirth, and macrosomia (ACOG 201 2018). 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 2021; Blumer 2013).
Agents other than gliclazide are currently recommended to treat diabetes mellitus in pregnancy (ADA 2021).
It is not known if gliclazide is present in breast milk.
Use is contraindicated in breastfeeding mothers.
Should be taken with meals. Individualized medical nutrition therapy (MNT) based on CDA recommendations is an integral part of therapy.
Signs and symptoms of hypoglycemia, fasting blood glucose, blood glucose self-monitoring; 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 and hepatic function (baseline [all patients] then periodically thereafter in patients with mild-moderate dysfunction)
Recommendations for glycemic control in patients with diabetes:
Nonpregnant adults (ADA 2020):
HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics).
Preprandial capillary blood glucose: 80 to 130 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).
Peak postprandial capillary blood glucose: <180 mg/dL (more or less stringent goals may be appropriate based on patient-specific characteristics).
Older adults (≥65 years of age) (ADA 2020):
Note: Consider less strict targets in patients who are using insulin and/or insulin secretagogues (eg, sulfonylureas) (ES [LeRoith 2019]).
HbA1c: <7.5% (healthy); <8% (complex/intermediate health); <8.5% (very complex/poor health) (individualization may be appropriate based on patient and caregiver preferences and/or presence of cognitive impairment).
Preprandial capillary blood glucose: 90 to 130 mg/dL (healthy); 90 to 150 mg/dL (complex/intermediate health); 100 to 180 mg/dL (very complex/poor health).
Bedtime capillary blood glucose: 90 to 150 mg/dL (healthy); 100 to 180 mg/dL (complex/intermediate health); 110 to 200 mg/dL (very complex/poor health).
Classification of hypoglycemia (ADA 2020):
Level 1: ≥54 to ≤70 mg/dL; hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.
Level 2: <54 mg/dL; threshold for neuroglycopenic symptoms; requires immediate action.
Level 3: Hypoglycemia associated with a severe event characterized by altered mental and/or physical status requiring assistance.
Stimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites.
Duration of action: Modified-release tablet: 24 hours
Absorption: Immediate-release formulation: Rapid; Modified-release formulation: Slow and complete
Bioavailability: Modified release: 97%
Distribution: Vd: 20% to 40% of body weight
Protein binding: ~94% to 95%
Metabolism: Hepatic (via CYP2C9 and CYP2C19; Elliot 2007) to inactive metabolites
Half-life elimination: Immediate-release tablet: 10.4 hours; Modified-release tablet: 16 hours (range: 12 to 20 hours)
Time to peak: Immediate-release tablet: 4 to 6 hours; Modified-release tablet: ~6 hours
Excretion: Urine (60% to 70%; <1% as unchanged drug); feces (10% to 20%) as metabolites