Miglitol

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
Brands: Glyset

Introduction

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

Uses for Miglitol

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

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Metformin generally recommended over other antidiabetic agents for initial oral antidiabetic therapy because of absence of weight gain or hypoglycemia, relatively lower expense and greater efficacy, and generally low adverse effect profile.92

A consensus group of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes recommends addition of a basal insulin or a sulfonylurea as second-line therapy in patients inadequately controlled on metformin monotherapy.92 Alternative but less well-validated second-line agents that can be added to metformin and lifestyle changes are pioglitazone (e.g., for patients in whom hypoglycemia is particularly undesirable) or exenatide (e.g., for patients in whom hypoglycemia is undesirable or to promote weight loss in patients close to target HbA1c concentration [<8%]).92 α-Glucosidase inhibitors (e.g., acarbose, miglitol), amylin agonists (e.g., pramlintide), dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g., sitagliptin), or meglitinides (e.g., repaglinide, nateglinide) generally are not recommended as first- or second-line antidiabetic therapy because of relative lesser efficacy, limited clinical data, frequent adverse GI effects, and/or greater cost.92

Miglitol not effective as sole antidiabetic therapy in patients whose diabetes may be complicated by ketoacidosis (e.g., type 1 diabetes mellitus); instead, such patients should receive insulin.1 41 (See Contraindications under Cautions.)

Miglitol Dosage and Administration

General

  • Individualize treatment based on efficacy and tolerance and adjust target blood glucose and glycosylated hemoglobin (HbA1c) 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).1 41 91

  • Goal of therapy is to reduce both postprandial blood glucose concentrations and HbA1c concentrations to normal or near normal (<7%) using lowest effective dosage of miglitol as monotherapy or combined with a sulfonylurea antidiabetic agent.1 41 (Plasma glucose concentrations generally 10–15% higher than those in whole blood and may vary according to method and laboratory used.)94 During therapy initiation and dosage titration, obtain 1-hour postprandial glucose concentration to determine therapeutic response and minimum effective dosage.1 Monitor HbA1c concentrations approximately every 3 months to evaluate long-term glycemic control.1 41 Monitor glucose concentrations 1–2 hours after the start of a meal in those who have elevated HbA1c concentrations despite adequate preprandial glucose concentrations.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

Diabetes Mellitus
Monotherapy
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 HbA1c 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 HbA1c concentrations) at the maximum recommended dosage, consider lowering dosage.1 Once an effective and tolerated dosage is reached, maintain that dosage.1

Combination Therapy with a Sulfonylurea
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 HbA1c 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 HbA1c concentrations) at the maximum recommended dosage, consider lowering dosage.1 Once an effective and tolerated dosage is reached, maintain that dosage.1

Reduce dosage of concomitant sulfonylurea and/or miglitol if hypoglycemia occurs.1 93 95 (See Hypoglycemia under Cautions.)

Prescribing Limits

Adults

Diabetes Mellitus
Oral

Miglitol monotherapy: Maximum 100 mg 3 times daily.1

Combination therapy with a sulfonylurea: 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.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 or a sulfonylurea.1 93 95 If hypoglycemia occurs, adjust dosage of these agents appropriately.1 95 (See Combination Therapy with a Sulfonylurea 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

Category B.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 (Scr >2 mg/dL or Clcr <25 mL/minute); safety and efficacy not established.1 93 95

Common Adverse Effects

Flatulence, 1 2 13 16 93 soft stools/1 diarrhea,1 2 13 16 93 abdominal discomfort/pain.1 93

Interactions for Miglitol

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

Drug

Interaction

Comments

Amylase (digestive enzyme preparation)

Possible reduction in glycemic effects1 91

Avoid concomitant use1 91 93

Antacids

Pharmacokinetic interaction unlikely1 91

Charcoal (intestinal adsorbent)

Possible reduction in glycemic effects1 91

Avoid concomitant use1 91 93

Digoxin

Variable effects on plasma digoxin concentrations, depending on population subgroup1 91 93

Glyburide

(Also see entry for Sulfonylureas)

Possible decreased peak blood concentrations and AUC of glyburide1 91 93

Drug interaction not established, clinical importance unknown1 91 93

Insulin

Increased risk of hypoglycemia1 91 93

If hypoglycemia occurs, reduce dosage of insulin 1 91 93

Metformin

Minimal decrease in peak blood concentrations and AUC of metformin; no clinical effect on glycemic control1 38 91 93

Nifedipine

Pharmacokinetic or pharmacodynamic interaction unlikely1 91

Pancreatin (digestive enzyme preparation; no longer commercially available in the US)

Possible reduction in glycemic effects1 91

Avoid concomitant use1

Pramlintide

Pramlintide-induced slowing of gastric emptying may influence drug effects89

Concomitant use not recommended89

Propranolol

Reduction in bioavailability of propranolol1 91

Pharmacodynamic interaction unlikely93

Adjustment of propranolol dosage may be necessary93 95

Ranitidine

Reduction in bioavailability of ranitidine1 91

Adjustment of ranitidine dosage may be necessary93

Sulfonylureas

Increased risk of hypoglycemia1 95

Reduction in the insulinotropic and weight-increasing effects of sulfonylureas1 6

Additive glycemic effects1 6 7 16

If hypoglycemia occurs, reduce dosage of sulfonylurea and/or miglitol1 91 93 95

Used to therapeutic advantage1 6

Warfarin

Pharmacokinetic or pharmacodynamic interaction unlikely1 91 93

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 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.

Miglitol

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

25 mg

Glyset

Pfizer

50 mg

Glyset

Pfizer

100 mg

Glyset

Pfizer

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Glyset 100MG Tablets (PFIZER U.S.): 90/$125.99 or 270/$352.76

Glyset 25MG Tablets (PFIZER U.S.): 90/$111.99 or 270/$316.96

Glyset 50MG Tablets (PFIZER U.S.): 90/$120.00 or 270/$337.95

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions March 23, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Pfizer. Glyset (miglitol) tablets prescribing information. New York, NY; 2008 May.

2. Johnston PS, Lebovitz HE, Coniff RF et al. Advantages of α-glucosidase inhibition as monotherapy in elderly type 2 diabetic patients. J Clin Endocrinol Metab. 1998; 83:1515-22. [PubMed 9589648]

5. Taylor RH, Barker HM, Bowey EA et al. Regulation of the absorption of dietary carbohydrate in man by two new glycosidase inhibitors. Gut. 1986; 27:1471-8. [PubMed 3804023]

6. Johnston PS, Santiago JV, Coniff RF et al. Effects of the carbohydrase inhibitor miglitol in sulfonylurea-treated NIDDM patients. Diabetes Care. 1994; 17:20-9. [PubMed 8112185]

7. Lebovitz HE. Oral antidiabetic agents: the emergence of α-glucosidase inhibitors. Drugs. 1992; 44 (Suppl 3):21-8. [PubMed 1280574]

8. Hans-Jurgen A, Boberg M, Brendel E et al. Pharmacokinetics of miglitol: absorption, distribution, metabolism, and excretion following administration to rats, dogs, and man. Arzneimittlforschung. 1997; 47:734-45.

10. Reuser AJJ, Wisselaar HA. An evaluation of the potential side-effects of α-glucosidase inhibitors used for the management of diabetes mellitus. Eur J Clin Invest. 1994; 24 (Suppl 3):19-24. [PubMed 8001622]

13. Pagano G, Marena S, Corgiat-Mansin L et al. Comparison of miglitol and glibenclamide in diet-treated type 2 diabetic patients. Diabete Metabol. 1995; 21:162-7.

16. Segal P, Feig PU, Schernthaner G et al. The efficacy and safety of miglitol therapy compared with glibenclamide in patients with NIDDM inadequately controlled by diet alone. Diabetes Care. 1997; 20:687-91. ( [PubMed 9135927]

38. Lebovitz HE. α-Glucosidase inhibitors as agents in the treatment of diabetes. Diabetes Reviews. 1998; 6:132-45.

41. American Diabetes Association. Standards of medical care in diabetes--2009. Diabetes Care. 2009; 32 Suppl 1:S13-61.

88. Van De Laar F, Lucassen PL, Akkermans RP et al. α-Glucosidase inhibitors for patients with type 2 diabetes: results from a Cochrane systematic review and meta-analysis. Diabetes Care. 2005; 28:154-63. [PubMed 15616251]

89. Amylin Pharmaceuticals. Symlin (pramlintide acetate) injection prescribing information. San Diego, CA; 2007 Dec.

91. Campbell LK, Baker DE, Campbell RK. Miglitol: assessment of its role in the treatment of patients with diabetes mellitus. Ann Pharmacother. 2000; 34:1291-301. [PubMed 11098345]

92. Nathan DM, Buse JB, Davidson MB et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009; 32:193-203. [PubMed 18945920]

93. Scott LJ, Spencer CM. Miglitol: a review of its therapeutic potential in type 2 diabetes mellitus. Drugs. 2000; 59:521-49. [PubMed 10776834]

94. Knudson PE, Weinstock RS, Henry JB. Carbohydrates. In: Henry JB, ed. Clinical diagnosis and management by laboratory methods. 20th ed. Philadelphia: WB Saunders; 2001:214.

95. Pfizer, New York, NY: Personal communication.

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