Miglitol (Monograph)

Brand name: Glyset
Drug class: alpha-Glucosidase Inhibitors
VA class: HS502
Chemical name: [2R-(2α,3β,4α,5β]-1-(2-hydroxyethyl)-2-(hydroxymethyl)-3,4,5-piperidinetriol
Molecular formula: C₈H₁₇NO₅
CAS number: 72432-03-2

Medically reviewed by Drugs.com on Jun 11, 2024. Written by ASHP.

Introduction

Antidiabetic agent; an α-glucosidase inhibitor.^{1 6 16 38}

Uses for Miglitol

Type 2 Diabetes Mellitus

Used as monotherapy as an adjunct to diet and exercise for management of type 2 diabetes mellitus in patients whose hyperglycemia cannot be controlled by diet and exercise alone.^{1 2 13 16 38}

Also used as an adjunct to diet and exercise in combination with a sulfonylurea for management of type 2 diabetes mellitus in patients whose hyperglycemia cannot be controlled with miglitol or sulfonylurea monotherapy, diet, and exercise.^{1 6}

Current guidelines for the treatment of type 2 diabetes mellitus generally recommend metformin as first-line therapy in addition to lifestyle modifications in patients with recent-onset type 2 diabetes mellitus or mild hyperglycemia because of its well-established safety and efficacy (i.e., beneficial effects on glycosylated hemoglobin [hemoglobin A1c; HbA_1c], weight, and cardiovascular mortality).^{698 704 705}

An α-glucosidase inhibitor (acarbose, miglitol) generally not recommended as second-line therapy after failure of metformin monotherapy because of comparatively lesser efficacy, frequent adverse GI effects, and greater cost, but may be appropriate therapy in selected patients.^{92 698}

In patients with metformin contraindications or intolerance (e.g., risk of lactic acidosis, GI intolerance) or in selected other patients, some experts suggest that initial therapy with a drug from another class of antidiabetic agents (e.g., a GLP-1 receptor agonist, sodium-glucose cotransporter 2 [SGLT2] inhibitor, dipeptidyl peptidase-4 [DPP-4] inhibitor, sulfonylurea, thiazolidinedione, basal insulin) may be acceptable based on patient factors.^{698 704}

May need to initiate therapy with 2 agents (e.g., metformin plus another drug) in patients with high initial HbA_1c (>7.5% or ≥1.5% above target).^{698 704} In such patients with metformin intolerance, some experts suggest initiation of therapy with 2 drugs from other antidiabetic drug classes with complementary mechanisms of action. ^{698 704}

Consider early initiation of combination therapy for the treatment of type 2 diabetes mellitus to extend the time to treatment failure and more rapidly attain glycemic goals.⁷⁰⁴

For patients with inadequate glycemic control on metformin monotherapy, consider patient comorbidities (e.g., atherosclerotic cardiovascular disease [ASCVD], established kidney disease, heart failure), hypoglycemia risk, impact on weight, cost, risk of adverse effects, and patient preferences when selecting additional antidiabetic agents for combination therapy.^{698 704 705 706}

Consider early introduction of insulin for severe hyperglycemia (e.g., blood glucose ≥300 mg/dL or HbA_1c >9–10%), especially if accompanied by catabolic manifestations (e.g., weight loss, hypertriglyceridemia, ketosis) or symptoms of hyperglycemia.^{698 704}

Miglitol Dosage and Administration

General

• Individualize treatment based on efficacy and tolerance^{1 41 91} and adjust target blood glucose and glycosylated hemoglobin (HbA_1c) concentrations based on patient’s understanding and adherence to the treatment regimen, the risk of severe hypoglycemia, and other factors that may increase risk or decrease benefit (e.g., very young or old age, comorbid conditions, other diseases that materially shorten life expectancy).^{41 91}

• Goal of therapy is to reduce both postprandial blood glucose concentrations and HbA_1c concentrations to normal or near normal (<7%) using lowest effective dosage of miglitol as monotherapy or combined with a sulfonylurea antidiabetic agent.^{1 41 94} During therapy initiation and dosage titration, obtain 1-hour postprandial glucose concentration to determine therapeutic response and minimum effective dosage.¹ Monitor HbA_1c concentrations approximately every 3 months to evaluate long-term glycemic control.^{1 41}

Administration

Administer orally.^{1 6 16}

Oral Administration

Administer at the beginning (with the first bite) of each main meal.^{1 38}

Dosage

Adults

Type 2 Diabetes Mellitus

Oral

Initially, 25 mg 3 times daily at the beginning of each main meal.¹ To minimize adverse GI effects in patients who may have GI sensitivity to miglitol, initiate therapy with 25 mg once daily and increase gradually (e.g., over 4 weeks) as tolerated to 25 mg 3 times daily.^{1 91 95}

After 4–8 weeks at 25 mg 3 times daily, increase dosage as tolerated to 50 mg 3 times daily,¹ the usual maintenance dosage.^{1 93} If response (i.e., as determined by HbA_1c concentrations ) is not adequate after 3 months, increase dosage to 100 mg 3 times daily, the maximum recommended daily dosage.^{1 95} If no further therapeutic benefit occurs (i.e., as determined by postprandial glucose or HbA_1c concentrations) at the maximum recommended dosage, consider lowering dosage.¹ Once an effective and tolerated dosage is reached, maintain that dosage.¹

In patients receiving concomitant sulfonylurea therapy, reduce dosage of sulfonylurea and/or miglitol if hypoglycemia occurs.^{1 93 95} (See Hypoglycemia under Cautions.)

Prescribing Limits

Adults

Type 2 Diabetes Mellitus

Oral

Maximum 100 mg 3 times daily.¹

Special Populations

Hepatic Impairment

Not metabolized; dosage adjustments not required.^{1 38 91}

Renal Impairment

Accumulation of miglitol expected in patients with renal impairment.^{1 10 91 95} However, as miglitol acts locally in the small intestine, reduction of elevated plasma concentrations through dosage adjustments in such patients is not feasible.^{1 5 10 38 91 95} (See Renal Impairment under Cautions.)

Geriatric Patients

No dosage adjustment required based solely on age.^{1 93}

Cautions for Miglitol

Contraindications

• Known hypersensitivity to the drug or any excipients in the formulation.¹

• Diabetic ketoacidosis.^{1 93}

• Inflammatory bowel disease, colonic ulceration, partial intestinal obstruction or predisposition to this condition.¹

• Chronic intestinal diseases associated with marked disorders of digestion or absorption.¹

• Co-existing conditions that may deteriorate as a result of increased intestinal gas formation.¹

Warnings/Precautions

General Precautions

Hypoglycemia

Miglitol should not cause hypoglycemia when administered alone in the fasting or postprandial state.^{1 2 16 91 93 95} Increased risk of hypoglycemia when used concomitantly with insulin^{† [off-label]} or a sulfonylurea.^{1 93 95} If hypoglycemia occurs, adjust dosage of these agents appropriately.^{1 95} (See Dosage under Dosage and Administration.)

Use oral glucose (dextrose) for the treatment of mild to moderate hypoglycemia instead of sucrose (table sugar, a disaccharide);^{1 91 93} absorption of oral glucose (a monosaccharide) is not delayed by miglitol.^{1 93 95} (See Actions.) Severe hypoglycemia may require the use of either IV glucose infusion or parenteral glucagon.^{1 91 95}

Loss of Glycemic Control

Possible loss of glycemic control during periods of stress (e.g., fever, trauma, infection, surgery); temporary administration of insulin may be required.^{1 95}

Specific Populations

Pregnancy

Safety not established in pregnant women.¹ Use during pregnancy only when clearly needed.¹

Lactation

Distributed into milk in low concentrations; use not recommended in nursing women.^{1 91 93}

Pediatric Use

Safety and efficacy not established in pediatric patients.¹

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.^{1 93}

Renal Impairment

Not recommended for use in patients with substantial renal impairment (S_cr >2 mg/dL or Cl_cr <25 mL/minute); safety and efficacy not established.^{1 93 95}

Common Adverse Effects

Flatulence, ^{1 2 13 16 93 1} diarrhea,^{1 2 13 16 93} abdominal discomfort/pain.^{1 93}

Drug Interactions

Carbohydrate-Splitting Digestive Enzyme Supplements

Possible reduction in glycemic effects of miglitol.^{1 91} Avoid concomitant use.^{1 91}

Intestinal Adsorbents

Possible reduction in glycemic effects of miglitol.^{1 91} Avoid concomitant use.^{1 91}

Specific Drugs

Miglitol Pharmacokinetics

Absorption

Bioavailability

Absorbed via an active transport system that is saturable at high dosages.^{1 7 8 38 91 93 95} Bioavailability 100 or 50–70% following administration of 25- or 100-mg dose, respectively.^{1 91}

Peak plasma concentrations attained within 2–3 hours.^{1 8 91 93}

Therapeutic effects principally result from local actions on small intestine; no evidence that systemic absorption contributes to therapeutic response.^{1 16 38 91}

Duration

Reduction in postprandial blood glucose concentrations persists for 3–4 hours following single dose in healthy individuals.⁹³

Special Populations

Since miglitol excreted principally by kidneys, accumulation expected in patients with renal impairment.^{1 10 91 95} (See Renal Impairment under Cautions.)

Distribution

Extent

Distributed principally into extracellular fluid ^{1 8 91 93} and concentrated in enterocytes of small intestine.^{8 38}

Crosses placenta and is distributed into milk in low concentrations (0.02% of a 100-mg dose).^{1 8 93}

Very low permeation of blood-brain barrier in animals.^{8 91 93}

Plasma Protein Binding

<4%.^{1 91}

Elimination

Metabolism

Not metabolized.^{1 8 38 91}

Elimination Route

Following oral administration of 25 mg, excreted principally in urine (95%) as unchanged drug.^{1 8 91 93}

Half-life

Approximately 2–3 hours in healthy individuals over therapeutic dosage range.^{8 91 93}

Special Populations

Pharmacokinetics not altered in patients with cirrhosis;^{1 91} miglitol not metabolized.^{1 8}

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹

Actions

• Inhibits α-glucosidase enzymes (e.g., sucrase, glucoamylase, maltase, isomaltase) that hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in small intestinal brush-border.^{1 5 10 38 91} Little or no inhibitory effect on trehalase, lactase, or pancreatic α-amylase; not expected to produce lactose intolerance.^{1 10 38 91 93}

• Delays ingested carbohydrate breakdown and glucose absorption and reduces postprandial hyperglycemia in diabetic patients.^{1 6 7 38 91 93}

• Fasting blood glucose concentrations mildly decreased.^{1 2 7 13 38 88 93}

• In contrast to sulfonylurea antidiabetic agents, miglitol does not enhance insulin secretion.^{1 2 13 16 91 93} Does not produce hypoglycemia when given as monotherapy in fasted or postprandial state.^{1 2 16}

• When used in combination with sulfonylurea antidiabetic agents, miglitol reduces the insulinotropic and weight-increasing effects of sulfonylureas.^{1 6} Does not produce clinically important weight loss.⁶

Advice to Patients

• Importance of adherence to diet and exercise regimen.^{1 91 93}

• Importance of regular monitoring of blood glucose concentrations.^{1 91 93}

• Provide instruction on the management of hypoglycemia.^{1 41} Advise of risk of hypoglycemia, its symptoms, and conditions that predispose to the development of hypoglycemia.¹ Importance of keeping a readily available source of glucose (dextrose) to treat symptoms of hypoglycemia when used in combination with insulin or a sulfonylurea agent.^{1 91}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of advising patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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