Skip to Content
Print Share

Chlorpropamide

Class: Sulfonylureas
ATC Class: A10BB02
VA Class: HS502
CAS Number: 94-20-2
Brands: Diabinese

Medically reviewed by Drugs.com. Last updated on June 22, 2020.

Introduction

Antidiabetic agent; sulfonylurea.189 a

Uses for Chlorpropamide

Diabetes Mellitus

Used as monotherapy as an adjunct to diet and exercise for management of type 2 (noninsulin-dependent) diabetes mellitus in patients whose hyperglycemia cannot be controlled with diet and exercise alone.189 a

Used as second-line therapy in combination with one or more other oral antidiabetic agents or insulin as an adjunct to diet and exercise in patients with type 2 diabetes mellitus in whom adequate glycemic control cannot be achieved with oral antidiabetic agent monotherapy.135 145 146 147 148 149 169 170 171 172 173 174 175 176 177 178 179 180

Alternative therapy in some type 2 diabetic patients being treated with insulin or other antidiabetic agent(s).189 a Useful in combination with insulin to improve glycemic control and/or decrease insulin dosage in some type 2 diabetic patients.135 145 146 150 151 153 154 155 156 157 158

Not effective as sole therapy in patients with type 1 diabetes mellitus or diabetic acidosis, ketosis, or coma; 101 103 106 insulin is necessary.101 102 106 (See Contraindications under Cautions.)

Not routinely recommended in hospitalized patients with diabetes mellitus.122 Long duration of action precludes rapid dosage adjustments.122 Increased risk of hypoglycemia in hospitalized diabetic patients with irregular eating patterns.122

Chlorpropamide Dosage and Administration

General

  • Adjust dosage according to severity of disease, tolerance, and blood glucose determinations.189 a

  • Monitor regularly (e.g., blood glucose concentrations) to determine minimum effective dosage and to detect primary failure or secondary failure.189 a (See Loss of Glycemic Control under Cautions.)

  • Monitor glycosylated hemoglobin (HbA1c) to determine patient’s continued response to therapy.189

  • Administration of loading dose is not recommended.189 a

  • During transfer from insulin therapy, patients should test their blood glucose concentrations ≥3 times daily.189 (See Advice to Patients.) Early hypoglycemia (≤24 hours) following transfer from intermediate or long-acting insulins usually results from insulin carry-over rather than from chlorpropamide.189 a In some patients, consider hospitalization during transition period.189 a

Administration

Oral Administration

Administer orally as a single daily dose each morning with breakfast.189 a May administer in 2 divided doses if GI intolerance occurs.189 a

Dosage

Adults

Diabetes Mellitus
Initiation
Oral

Initially, 250 mg daily.189 a

Initial Dosage in Patients Transferred from Other Oral Antidiabetic Agents
Oral

Initially, 250 mg daily.189 a May abruptly discontinue the other oral antidiabetic agent.189 a

Initial Dosage in Patients Transferred from Insulin
Oral

Insulin requirements ≤40 units daily: Initially, 250 mg daily.189 a Abruptly discontinue insulin.189 a

Insulin requirements >40 units daily: Initially, 250 mg daily; reduce daily insulin dosage by 50% for first few days.189 a Subsequently, adjust insulin dosage according to therapeutic response.189 a

Titration and Maintenance Dosage
Oral

5–7 days after initiating therapy, titrate dosage in increments or decrements of ≤50–125 mg daily at 3- to 5-day intervals to achieve adequate glycemic control; more frequent dosage adjustments usually undesirable.189

Usual maintenance dosage is 100–500 mg daily.189 a Patients not responding to 500 mg daily are unlikely to respond to higher dosages.189 a

Prescribing Limits

Adults

Diabetes Mellitus
Oral

Maximum 750 mg daily.189 a

Special Populations

Hepatic Impairment

Use conservative initial and maintenance dosages to avoid hypoglycemia.189 (See Hepatic Impairment under Cautions.)

Renal Impairment

Use conservative initial and maintenance dosages to avoid hypoglycemia.189 (See Renal Impairment under Cautions.)

Geriatric Patients

Initially, 100–125 mg daily.189 Use conservative initial and maintenance dosages to avoid hypoglycemia.189 (See Geriatric Use under Cautions.)

Debilitated or Malnourished Patients

Use conservative initial and maintenance dosages to avoid hypoglycemia.189

Pituitary or Adrenal Insufficiency

Use conservative initial and maintenance dosages to avoid hypoglycemia.189

Detailed Chlorpropamide dosage information

Cautions for Chlorpropamide

Contraindications

  • Known hypersensitivity to chlorpropamide or any ingredient in formulation.189

  • Diabetic ketoacidosis with or without coma.189 a

  • Monotherapy for type 1 diabetes mellitus.189 a

Warnings/Precautions

Warnings

Cardiovascular Effects

Increased cardiovascular mortality reported with certain other antidiabetic agents (i.e., tolbutamide, phenformin).111 189 d However, ADA considers benefits of intensive glycemic control with insulin or sulfonylureas to outweigh the risks overall.112 115 128

General Precautions

Hypoglycemia

Possible severe hypoglycemia, especially in geriatric, debilitated, or malnourished patients and those with adrenal, pituitary, hepatic, or renal insufficiency.189 a d Increased risk of hypoglycemia with strenuous exercise, alcohol ingestion, insufficient caloric intake, or concurrent drug use (e.g., other antidiabetic agents, agents that enhance hypoglycemic effects).189 d (See Specific Drugs under Interactions.)

Higher incidence of hypoglycemia at therapeutic dosages with chlorpropamide than other sulfonylureas;c may result from prolonged duration of action.c d (See Duration under Pharmacokinetics.)

Hypoglycemia may be difficult to recognize in geriatric patients and those receiving β-adrenergic blocking agents.189

Appropriate patient selection and careful dosing and instructions are important to avoid chlorpropamide-induced hypoglycemia.189

Hypoglycemia may result in coma, seizures, or other neurologic impairment.189 a d

If hypoglycemia occurs, immediately reevaluate patient and adjust insulin or chlorpropamide dosage.a Monitor patient for 24–48 hours;189 may require hospitalization and IV glucose.189 a Carefully supervise dose and give frequent feedings for ≥3–5 days.189

Loss of Glycemic Control

Possible loss of glycemic control during periods of stress (e.g., fever, trauma, infection, surgery).101 102 105 106 189 May require use of insulin and/or temporary discontinuance of chlorpropamide.189 a

Efficacy of therapy may decrease over time (secondary failure); evaluate patients at regular intervals.189 a

Assess patient for adequate adjustment of dose and adherence to diet before attributing inadequate response to secondary failure of the drug.189

Manufacturer recommends discontinuance of chlorpropamide if loss of satisfactory glycemic control develops.189 ADA and other clinicians recommend addition of other oral antidiabetic agents or insulin.127 146 173 175 184 185 186 191 192 (See Diabetes Mellitus under Uses.)

Specific Populations

Pregnancy

Category C.189

Prolonged (4–10 days), severe hypoglycemia reported in some neonates born to women receiving a sulfonylurea at delivery;189 more frequent with long-acting sulfonylureas (e.g., chlorpropamide).189 Discontinue drug ≥1 month before expected delivery date to minimize the risk of neonatal hypoglycemia.189

Many experts recommend the use of insulin during pregnancy.189

Lactation

Distributed into milk.189 Use not recommended.189

Pediatric Use

Safety and efficacy not established.189

Geriatric Use

Safety and efficacy not established.189 Increased risk of hypoglycemia and/or hyponatremia; hypoglycemia may be difficult to recognize.189 d Cautious dosing recommended.189 (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Diminished gluconeogenic capacity and increased risk of hypoglycemia; conservative dosing recommended.189 a (See Hepatic Impairment under Dosage and Administration.)

Monitor liver function frequently during chlorpropamide initiation.a

Renal Impairment

Increased risk of hypoglycemia; conservative dosing recommended.189 a (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Hypoglycemia,111 189 a nausea,189 a weight gain.111 142 143 144

Interactions for Chlorpropamide

Metabolized mainly by CYP2C9.c (See Elimination under Pharmacokinetics.)

Protein-bound Drugs

Potential pharmacokinetic interaction (increased hypoglycemic effect because of displacement of chlorpropamide from binding sites on proteins).189 a (See Specific Drugs under Interactions.)

Close observation recommended when initiating or discontinuing concomitant therapy with a highly protein-bound drug.189 a

Specific Drugs

Drug

Interaction

Comments

Alcohol

Disulfiram-like reactions reported189 a

Moderate-to-large amounts of alcohol may increase the risk of hypoglycemia189

If intolerant, attempt therapy with another sulfonylurea agenta

Antifungals, oral azoles (i.e., fluconazole, miconazole)

Increased plasma concentrations of sulfonylureas and hypoglycemic effect182 183 189

Not known whether interaction occurs with IV, topical, or vaginal miconazole189

Anticoagulants, oral

Possible potentiation of hypoglycemic effects189 a

Observe closely for hypoglycemia or loss of glycemic control when concurrent therapy initiated or discontinued189

Barbiturates

May prolong action of barbiturates189 a

Use concurrently with caution189 a

β-Adrenergic blocking agents

Possible potentiation of hypoglycemic effects189

Signs of hypoglycemia may be masked by β-adrenergic blocking agents189

Observe closely for hypoglycemia or loss of glycemic control when concurrent therapy is initiated or discontinued189

Calcium-channel blocking agents

Potential for decreased hypoglycemic effect189

Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189

Chloramphenicol

Possible potentiation of hypoglycemic effects189

Observe closely for hypoglycemia when concurrent therapy is initiated or discontinued189

Contraceptives, oral

Potential for decreased hypoglycemic effect189

Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189

Corticosteroids

Potential for decreased hypoglycemic effect189

Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189

Diuretics

Potential for decreased hypoglycemic effect189

Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189

Estrogens

Potential for decreased hypoglycemic effect189

Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189

Isoniazid

Potential for decreased hypoglycemic effect189

Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189

MAO inhibitors

Possible potentiation of hypoglycemic effects189

Observe closely for hypoglycemia or loss of glycemic control when concurrent therapy is initiated or discontinued189

Niacin

Potential for decreased hypoglycemic effect189

Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189

NSAIAs

Possible displacement of chlorpropamide from plasma proteins and potentiation of hypoglycemic effects189

Observe closely for hypoglycemia or loss of glycemic control when concurrent therapy initiated or discontinued189

Phenothiazines

Potential for decreased hypoglycemic effect189

Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189

Phenytoin

Potential for decreased hypoglycemic effect189

Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189

Probenecid

Possible potentiation of hypoglycemic effects189

Observe closely for hypoglycemia or loss of glycemic control when concurrent therapy initiated or discontinued189

Salicylates

Possible displacement of chlorpropamide from plasma proteins and potentiation of hypoglycemic effects189

Observe closely for hypoglycemia or loss of glycemic control when concurrent therapy initiated or discontinued189

Sulfonamides

Possible displacement of chlorpropamide from plasma proteins and potentiation of hypoglycemic effects189

Observe closely for hypoglycemia or loss of glycemic control when concurrent therapy initiated or discontinued189

Sympathomimetic agents

Potential for decreased hypoglycemic effect189

Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189

Thyroid agents

Potential for decreased hypoglycemic effect189

Observe closely for loss of glycemic control or hypoglycemia when concurrent therapy is initiated or discontinued189
Chlorpropamide drug interactions (more detail)

Chlorpropamide Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration; peak plasma concentrations attained within 2–4 hours.189 a b

Onset

In healthy individuals, hypoglycemic action begins ≤1 hour; maximal at 3–6 hours.189

Duration

In healthy individuals, hypoglycemic action persists for ≥24 hours;189 longest duration of action of the sulfonylureas.a d

Food

Food does not appear to affect absorption or bioavailability; decreases peak serum concentrations of drug.b

Special Populations

Following administration of a single dose in healthy elderly and young adult individuals, age did not affect pharmacokinetics of chlorpropamide.b

Distribution

Extent

Sulfonylureas are distributed into extracellular fluids.a

Chlorpropamide crosses the placenta and is distributed into milk.189 (See Pregnancy under Cautions.)

Plasma Protein Binding

Highly bound to plasma proteins.a

Elimination

Metabolism

Extensively metabolized, mainly by CYP2C9.c

Elimination Route

Excreted in urine (80–90%) mainly as metabolites.189 a c

Increased or decreased rate of elimination in alkaline or acidic urine, respectively.a c

Half-life

36 hours (range: 25–60 hours).189 a b c d

Special Populations

Renal or hepatic insufficiency may affect pharmacokinetics and increase the risk of serious hypoglycemic reactions.189

Metabolism influenced by CYP2C9 polymorphism; genetic differences in drug metabolism affect drug response.c

Stability

Storage

Oral

Tablets

<30°C.189

Actions

  • Stimulates secretion of postprandial endogenous insulin from beta cells of pancreas.189 a d

  • Ineffective in absence of functioning beta cells.189 a

  • During prolonged administration, extrapancreatic effects (e.g., enhanced peripheral sensitivity to insulin, reduction of basal hepatic glucose production) contribute to hypoglycemic action.189 a

Advice to Patients

  • Inform patients of potential risks and advantages of chlorpropamide therapy and alternative forms of treatment.189

  • Importance of regular testing of blood glucose concentrations and HbA1c values.189

  • During insulin withdrawal, importance of testing blood glucose concentrations ≥3 times daily.189 Importance of patients immediately informing clinicians of abnormal results for appropriate adjustments in therapy, if necessary.189

  • Importance of adhering to diet and exercise regimen.101 102 107 110 189

  • Importance of hygiene and avoidance of infection.a

  • Advise patients about nature of diabetes mellitus, prevention and detection of complications, and importance of glycemic control.a

  • Importance of understanding primary and secondary failure to therapy.189

  • Risks of hypoglycemia.189 Importance of patients and responsible family members understanding symptoms and treatment of hypoglycemic reactions and identifying conditions that predispose to development of such reactions.189

  • Risk of alcohol intolerance (e.g., facial flushing).a

  • Advise patients to use caution while driving and operating machinery.189

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.189

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.189

  • Importance of informing patients of other important precautionary information.189 (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

chlorproPAMIDE

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

100 mg*

Diabinese (scored)

Pfizer

250 mg*

Diabinese (scored)

Pfizer

AHFS DI Essentials™. © Copyright 2021, Selected Revisions July 1, 2008. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

Only references cited for selected revisions after 1984 are available electronically.

101. The Upjohn Company. Micronase (glyburide) prescribing information. Kalamazoo, MI; 1988 May.

102. Hoechst-Roussel Pharmaceuticals Inc. Diaβeta (glyburide) prescribing information. Somerville, NJ; 1987 Dec.

103. Anon. Glibenclamide: a review. Drugs. 1971; 1:116-40. http://www.ncbi.nlm.nih.gov/pubmed/5004340?dopt=AbstractPlus

104. DeFronzo RA, Ferrannini E, Koivisto V. New concepts in the pathogenesis and treatment of noninsulin-dependent diabetes mellitus. Am J Med. 1983; 74(Suppl 1A):52-81. http://www.ncbi.nlm.nih.gov/pubmed/6337486?dopt=AbstractPlus

105. National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes. 1979; 28:1039-57. http://www.ncbi.nlm.nih.gov/pubmed/510803?dopt=AbstractPlus

106. Koda-Kimble MA. Diabetes mellitus. In: Koda-Kimble MA, Young LY, eds. Applied therapeutics: the clinical use of drugs. 5th ed. Vancouver, WA: Applied Therapeutics, Inc.; 1992:72–1-53.

107. Scientific Advisory Panel of the Executive Committee, American Diabetes Association. Policy statement: the UGDP controversy. Diabetes. 1979; 28:168-70.

108. Jackson JE, Bressler R. Clinical pharmacology of sulphonylurea hypoglycaemic agents: part 2. Drugs. 1981; 22:295-320. http://www.ncbi.nlm.nih.gov/pubmed/7030708?dopt=AbstractPlus

109. Food and Drug Administration. Labeling for oral hypoglycemic drugs of the sulfonylurea class. [Docket No. 75N-0062] Fed Regist. 1984; 49:14303-31.

110. Skyler JS. Non-insulin-dependent diabetes mellitus: a clinical strategy. Diabetes Care. 1984; 7(Suppl 1):118-29. http://www.ncbi.nlm.nih.gov/pubmed/6376024?dopt=AbstractPlus

111. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998; 352:837-53. http://www.ncbi.nlm.nih.gov/pubmed/9742976?dopt=AbstractPlus

112. American Diabetes Association. Implications of the United Kingdom Prospective Diabetes Study. Diabetes Care. 1999; 22(Suppl 1):S27-31.

113. Matthews DR, Cull CA, Stratton RR et al. UKPDS 26: sulphonylurea failure in non-insulin-dependent diabetic patients over 6 years. Diabet Med. 1998; 15:297-303. http://www.ncbi.nlm.nih.gov/pubmed/9585394?dopt=AbstractPlus

114. Genuth P. United Kingdom prospective diabetes study results are in. J Fam Pract. 1998; 47:(Suppl 5):S27.

115. Bretzel RG, Voit K, Schatz H et al. The United Kingdom Prospective Diabetes Study (UKPDS): implications for the pharmacotherapy of type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 1998; 106:369-72. http://www.ncbi.nlm.nih.gov/pubmed/9831300?dopt=AbstractPlus

116. Schmitt JK, Moore JR. Hypertension secondary to chlorpropamide with amelioration by changing to insulin. Am J Hypertens. 1993; 6:317-9. http://www.ncbi.nlm.nih.gov/pubmed/8507452?dopt=AbstractPlus

117. Genuth S, Brownless MA, Kuller LH et al. Consensus development conference on insulin resistance: Novermber 5-6 1997. Diabetes Care. 1998; 21:310-4. http://www.ncbi.nlm.nih.gov/pubmed/9540000?dopt=AbstractPlus

118. Henry RR. Glucose control and insulin resistance in non-insulin-dependent diabetes mellitus. Ann Intern Med. 1996; 124:97-103. http://www.ncbi.nlm.nih.gov/pubmed/8554221?dopt=AbstractPlus

119. Lebovitz HE. Stepwise and combination drug therapy for the treatment of NIDDM. Diabetes Care. 1994; 17:1542-4. http://www.ncbi.nlm.nih.gov/pubmed/7882832?dopt=AbstractPlus

120. Nathan DM. Some answers, more controversy, from UKDS. Lancet. 1998; 352:832-3. http://www.ncbi.nlm.nih.gov/pubmed/9742972?dopt=AbstractPlus

121. Reviewers’ comments (personal observations) on metformin.

122. American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2006; 29(Suppl 1):S4-42.

123. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993; 329:977-86. http://www.ncbi.nlm.nih.gov/pubmed/8366922?dopt=AbstractPlus

124. Klein R, Klein BEK, Moss SE et al. Glycosylated hemoglobin predicts the incidence and progression of diabetic retinopathy. JAMA. 1988; 260:2864-71. http://www.ncbi.nlm.nih.gov/pubmed/3184351?dopt=AbstractPlus

125. American Diabetes Association. Implications of the diabetes control and complications trial. Diabetes Care. 1996; 19:50-2S.

126. Ohkubo Y, Kishikawa H, Araki E et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus; a randomized prospective 6-year study. Diabetes Res Clin Pract. 1995; 28:103-17. http://www.ncbi.nlm.nih.gov/pubmed/7587918?dopt=AbstractPlus

127. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998; 352:854-65. http://www.ncbi.nlm.nih.gov/pubmed/9742977?dopt=AbstractPlus

128. American Diabetes Association. The United Kingdom Prospective Diabetes Study (UKPDS) for type 2 diabetes: what you need to know about the results of a long-term study. Washington, DC; September 15, 1998. From American Diabetes Association web site. http://www.dtu.ox.ac.uk/ukpds

129. Davis TM. United Kingdom Prospective Diabetes Study: the end of the beginning? Med J Aust. 1998; 169:511-2.

130. Watkins PJ. UKPDS: a message of hope and a need for change. Diabet Med. 1998; 15:895-6. http://www.ncbi.nlm.nih.gov/pubmed/9827842?dopt=AbstractPlus

131. Turner RC, Cull CA, Frighi V et al. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirements for multiple therapies (UKPDS 49). JAMA. 1999; 281:2005-12. http://www.ncbi.nlm.nih.gov/pubmed/10359389?dopt=AbstractPlus

132. American Diabetes Association. Type 2 diabetes in children and adolescents. Pediatrics. 2000; 105:671-80. http://www.ncbi.nlm.nih.gov/pubmed/10699131?dopt=AbstractPlus

133. American Diabetes Association. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 2000; 23(Suppl 1):S4-19.

134. American Diabetes Association. Office guide to diagnosis and classification of diabetes mellitus and other categories of glucose intolerance. Diabetes Care. 1995; 18(Suppl 1):4.

135. Williams G. Management of non-insulin-dependent diabetes mellitus. Lancet. 1994; 343:95-100. http://www.ncbi.nlm.nih.gov/pubmed/7903785?dopt=AbstractPlus

136. Genuth S. Exogenous insulin administration and cardiovascular risk in non-insulin-dependent and insulin-dependent diabetes mellitus. Ann Intern Med. 1996;124(1 Part 2):104-9.

137. DeFronzo RA. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM. Diabetes. 1988; 37:667-87. http://www.ncbi.nlm.nih.gov/pubmed/3289989?dopt=AbstractPlus

138. Polonsky KS, Sturis J, Bell GI. Non-insulin-dependent diabetes mellitus-a genetically programmed failure of the beta cell to compensate for insulin resistance. N Engl J Med. 1996; 334:777-83. http://www.ncbi.nlm.nih.gov/pubmed/8592553?dopt=AbstractPlus

139. Swislocki A. Insulin resistance and hypertension. Am J Med Sci. 1990; 300:104-15. http://www.ncbi.nlm.nih.gov/pubmed/2206054?dopt=AbstractPlus

140. United Kingdom Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998; 317:703-13. http://www.ncbi.nlm.nih.gov/pubmed/9732337?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=28659&blobtype=pdf

141. UK Prospective Diabetes Study (UKPDS) Group. Efficacy of atenolol and captopril in reducing risk of macrovascular complications in type 2 diabetes mellitus: UKPDS 39. BMJ. 1998; 317:713-20. http://www.ncbi.nlm.nih.gov/pubmed/9732338?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=28660&blobtype=pdf

142. Haffner SM, Hanefeld M, Fischer S et al. Glibenclamide, but not acarbose, increase leptin concentrations parallel to changes in insulin in subjects with NIDDM. Diabetes Care. 1997; 20: 1430-4. http://www.ncbi.nlm.nih.gov/pubmed/9283792?dopt=AbstractPlus

143. Shi H, Moustaid-Moussa N, Wilkison WO et al. Role of the sulfonylurea receptor in regulating human adipocyte metabolism. FASEB J. 1999; 13:1833-8. http://www.ncbi.nlm.nih.gov/pubmed/10506587?dopt=AbstractPlus

144. Cheskin LJ, Bartlett SJ, Zayas R et al. Prescription medications: a modifiable contributor to obesity. South Med J. 1999; 92:898-904. http://www.ncbi.nlm.nih.gov/pubmed/10498166?dopt=AbstractPlus

145. Chow CC, Sorensen JP, Tsang LWW et al. Comparison of insulin with or without continuation of oral hypoglycemic agents in the treatment of secondary failure in NIDDM patients. Diabetes Care. 1995; 18:307-14. http://www.ncbi.nlm.nih.gov/pubmed/7555472?dopt=AbstractPlus

146. Zimmerman B, Espenshade J, Fujimoto W et al. The pharmacological treatment of hyperglycemia in NIDDM. Diabetes Care. 1996; 19:1510-18.

147. Expert Committee of the Canadian Diabetes Advisory Board. Clinical practice guidelines for treatment of diabetes mellitus. Can Med Assoc J. 1992; 147:697-712.

148. Raskin P. Combination therapy in NIDDM N Engl J Med. 1992; 327:1453-4. Editorial.

149. Pugh JA, Ramirez G, Wagner ML et al. Is combination sulfonylurea and insulin therapy useful in NIDDM patients? A metaanalysis. Diabetes Care. 1992; 15:953-9. http://www.ncbi.nlm.nih.gov/pubmed/1387073?dopt=AbstractPlus

150. Landstedt-Hallin L, Bolinder J, Adamson U et al. Comparison of bedtime NPH or preprandial regular insulin combined with glibenclamide in secondary sulfonylurea failure. Diabetes Care. 1995; 18:1183-6. http://www.ncbi.nlm.nih.gov/pubmed/7587856?dopt=AbstractPlus

151. Trischitta V, Italia S, Mazzarino S et al. Comparison of combined therapies in treatment of secon dary failure to glyburide. Diabetes Care. 1992; 15:539-42. http://www.ncbi.nlm.nih.gov/pubmed/1499473?dopt=AbstractPlus

152. Krentz AJ, Ferner RE, Bailey CJ. Comparative tolerability profiles of oral antidiabetic agents. Drug Safety. 1994; 11:223-41. http://www.ncbi.nlm.nih.gov/pubmed/7848543?dopt=AbstractPlus

153. Buse J. Combining insulin and oral agents. Am J Med. 2000; 108(Suppl 6A):23S-32S. http://www.ncbi.nlm.nih.gov/pubmed/10764847?dopt=AbstractPlus

154. Johnson JL, Wolf SL, Kabadi UM. Efficacy of insulin and sulfonylurea combination therapy in type II diabetes: a meta-analysis of the randomized placebo-controlled trials. Arch Intern Med. 1996; 156:259-64. http://www.ncbi.nlm.nih.gov/pubmed/8572835?dopt=AbstractPlus

155. Florence JA, Yeager BF. Treatment of type 2 diabetes mellitus. Am Fam Physician. 1999; 59:2835-44. http://www.ncbi.nlm.nih.gov/pubmed/10348076?dopt=AbstractPlus

156. Yki-Jarvinen H, Dressler A, Ziemen M et al. Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime HPH insulin during insulin combination therapy in type 2 diabetes. Diabetes Care. 2000; 23:1130-6 (IDIS 451244) http://www.ncbi.nlm.nih.gov/pubmed/10937510?dopt=AbstractPlus

157. Bastyr EJ, Johnson ME, Trautman ME et al. Insulin lispro in the treatment of patients with type 2 diabetes mellitus after oral agent failure. Clin Ther. 1999; 21:1703-4. http://www.ncbi.nlm.nih.gov/pubmed/10566566?dopt=AbstractPlus

158. DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999; 131:281-303. http://www.ncbi.nlm.nih.gov/pubmed/10454950?dopt=AbstractPlus

159. Eli Lilly and Company. Humalog\rm/ (insulin lispro, rDNA origin) injection prescribing information. Indianapolis, IN; 2000 May 1.

160. United Kingdom prospective diabetes study group. United Kingdom prospective diabetes study (UKPDS) 16: overview of 6 years’ therapy of type II diabetes: a progressive disease. Diabetes. 1995; 44:1240-58.

161. Bailey C, Turner R. Metformin. N Engl J Med. 1996; 334:374-9. http://www.ncbi.nlm.nih.gov/pubmed/8538710?dopt=AbstractPlus

162. Clark CM Jr. Where do we go from here? Ann Intern Med. 1996; 124(1 Part 2):184-6. Editorial.

163. Bloomgarden ZT. New and traditional treatment of glycemia in NIDDM. Diabetes Care. 1996; 19:295-9. http://www.ncbi.nlm.nih.gov/pubmed/8742586?dopt=AbstractPlus

164. Anon. Diabetes mellitus. NIH Cons Dev Conf Statement. 1986; 6:1-7.

165. Blake GH. Control of type II diabetes: reaping the rewards of exercise and weight loss. Postgrad Med. 1992; 92:129-32. http://www.ncbi.nlm.nih.gov/pubmed/1437899?dopt=AbstractPlus

166. Kerr CP. Improving outcomes in diabetes: a review of the outpatient care of NIDDM patients. J Fam Pract. 1995; 40:63-75. http://www.ncbi.nlm.nih.gov/pubmed/7807040?dopt=AbstractPlus

167. Turner R, Cull C, Holman R et al. United Kingdom Prospective Diabetes Study 17: a 9-year update of a randomized, controlled trial on the effect of improved metabolic control on complications in non-insulin-dependent diabetes mellitus. Ann Intern Med. 1996; 124(1 Pt 2):136-45. http://www.ncbi.nlm.nih.gov/pubmed/8554206?dopt=AbstractPlus

168. American Diabetes Association. Position Statement: implications of the United Kingdom Prospective Diabetes Study. Diabetes Care. 1999; 22(Suppl. 1):S27-S31.

169. Takeda Pharmaceuticals America. Actos (pioglitazone hydrochloride) tablets prescribing information. Lincolnshire, IL; 2002 July.

170. SmithKline Beecham. Avandia (rosiglitazone maleate) tablets prescribing information. Philadelphia, PA; 2002 May

171. Kipnes MS, Krosnick a, Rendell MS et al. Pioglitazone hydrochloride in combination with sulfonylurea therapy improves glycemic control in patients with type 2 diabetes mellitus: a randomized, placebo-controlled study. Am J Med. 2001; 111:10-7. http://www.ncbi.nlm.nih.gov/pubmed/11448655?dopt=AbstractPlus

172. Wolffenbuttel BHR, Gomist R, Squatrito S et al. Addition of low-dose rosiglitazone to sulphonylurea therapy improves glycaemic control in type 2 diabetic patients. Diabet Med. 2000; 17:40-7. http://www.ncbi.nlm.nih.gov/pubmed/10691158?dopt=AbstractPlus

173. Hermann LS, Schersten B, Bitzen PO et al. Therapeutic comparison of metformin and sulfonylurea, alone and in various combinations. Diabetes Care. 1994; 17:1100-9. http://www.ncbi.nlm.nih.gov/pubmed/7821128?dopt=AbstractPlus

174. Reaven GM, Johnston P, Hollenbeck CB et al. Combined metformin-sulfonylurea treatment of patients with noninsulin-dependent diabetes in fair to poor glycemic control. J Clin Endocrinol Metab. 1992; 74:1020-6. http://www.ncbi.nlm.nih.gov/pubmed/1569149?dopt=AbstractPlus

175. Hermann L. Biguanides and sulfonylureas as combination therapy in NIDDM. Diabetes Care. 1990; 13:37-41. http://www.ncbi.nlm.nih.gov/pubmed/2209342?dopt=AbstractPlus

176. Chiasson J, Josse R, Hunt J et al. The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus. Ann Intern Med. 1994; 121:929-935.

177. Coniff RF, Shapiro JA, Seaton TB et al. Multicenter, placebo-controlled trial comparing acarbose (BAY g 5421) with placebo, tolbutamide, and tolbutamide-plus-acarbose in non-insulin-dependent diabetes mellitus. Am J Med. 1995; 98:443-51. http://www.ncbi.nlm.nih.gov/pubmed/7733122?dopt=AbstractPlus

178. Calle-Pascual AL, Garcia-Honduvilla J, Martin-Alvarez PJ et al. Comparison between acarbose, metformin, and insulin treatment in type 2 diabetic patients with secondary failure to sulfonylurea treatment. Diabetes Metab. 1995; 21:256-60.

179. Klein W. Sulfonylurea-metformin-combination versus sulfonylurea-insulin-combination in secondary failures of sulfonylurea monotherapy. Diab Metab. 1991; 17(Suppl 1):235-40.

180. Bristol-Myers-Squibb. Glucovance(glyburide and metformin hydrochloride) tablets prescribing information. Princeton, NJ; 2002 Oct.

181. Albengres E, Le Louet H, Tillement JP. Systemic antifungal agents. Drug interactions of clinical significance. Drug Saf. 1998; 18:83-97. http://www.ncbi.nlm.nih.gov/pubmed/9512916?dopt=AbstractPlus

182. Pfizer Inc. Glucotrol XL(glipizide) extended release tablets prescribing information. New York, NY; 2001 Apr.

183. Pfizer. Diflucan (fluconazole) tablets, for oral suspension, and injection prescribing information. New York, NY; 1998 Jun.

184. Hermann LS, Melander A. Biguanides: basic aspects and clinical use. In: Alberti KGMM, DeFronzo RA, Keen H et al, eds. International textbook of diabetes mellitus. New York: John Wiley & Sons; 1992; 773-95.

185. Moses R, Carter J, Slobodniuk R et al. Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 1999; 22:119-24. http://www.ncbi.nlm.nih.gov/pubmed/10333912?dopt=AbstractPlus

186. Fonseca V,, Rosenstock J, Patwardhan R et al. Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial. JAMA. 2000; 283:1695-702. http://www.ncbi.nlm.nih.gov/pubmed/10755495?dopt=AbstractPlus

187. Bristol-Myers Squibb. Glucophage (metformin hydrochloride) tablets and Glucophage XR (metformin hydrochloride) extended-release tablets prescribing information. Princeton, NJ; 2001 Jun.

188. Bayer. Precose (acarbose) tablets prescribing information. West Haven, CT; 2004 Nov.

189. Pfizer Labs. Diabinese (chlorpropamide) tablets prescribing information. New York, NY; 2006 Apr.

190. American Diabetes Association. Preconception care of women with diabetes. Diabetes Care. 2004; 27(Suppl 1):S76-78.

191. Nathan DM, Buse JB, Davidson MB et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2006; 29:1963-72. http://www.ncbi.nlm.nih.gov/pubmed/16873813?dopt=AbstractPlus

192. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Canadian Diabetes Association 2003 clinical paractuce guidelines for the prevention and management of diabetes in Canada. Can J Diabetes. 2003; 27(Suppl 2):S1-152.

a. AHFS drug information 2008. McEvoy GK, ed. Chlorpropamide. Bethesda, MD: American Society of Health-System Pharmacists; 2008:3231-5.

b. Sartor G, Melander A, Schersten B et al. Influence of food and age on the single-dose kinetics and effects of tolbutamide and chlorpropamide. Eur J Clin Pharmacol. 1980; 17:285-93. http://www.ncbi.nlm.nih.gov/pubmed/6995130?dopt=AbstractPlus

c. Shon JH, Yoon YR, Kim MJ et al. Chlorpropamide 2-hydroxylation is catalysed by CYP2C9 and CYP2C19 in vitro: chlorpropamide disposition is influenced by CYP2C9, but not by CYP2C19 genetic polymorphism. Br J Clin Pharmacol. 2005; 59:552-63. http://www.ncbi.nlm.nih.gov/pubmed/15842554?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1884838&blobtype=pdf

d. Spiller HA, Sawyer TS. Toxicology of oral antidiabetic medications. Am J Health-Syst Pharm. 2006; 63:929-38. http://www.ncbi.nlm.nih.gov/pubmed/16675650?dopt=AbstractPlus

Medical Disclaimer