eMedicine Specialties > Endocrinology > Metabolic Disorders

Insulin Resistance: Treatment & Medication

Author: Samuel T Olatunbosun, MD, FACP, Chief, Internal Medicine, 56th Medical Group, Luke Air Force Base
Coauthor(s): Samuel Dagogo-Jack, MD, MBBS, MSc, FRCP, Professor of Medicine, Program Director, Division of Endocrinology, Diabetes and Metabolism, University of Tennessee Health Science Center
Contributor Information and Disclosures

Updated: Nov 2, 2009

Treatment

Medical Care

Evaluate patients for comorbid conditions; this is generally feasible on an outpatient basis. Admission for laboratory studies may be warranted for patients whose conditions require urgent or emergent intervention.

The metabolic syndrome requires aggressive control of cardiovascular and metabolic risk factors. Tailor therapy for optimal benefits.

Surgical Care

  • Improvement in insulin resistance occurs after bariatric surgery, such as gastric banding and gastric bypass, when carried out in carefully selected morbidly obese patients.19
  • In severe cardiovascular disease, procedures such as coronary artery bypass graft and peripheral vascular surgery may be necessary.
  • Wedge resection has largely been abandoned, but it was once thought to be beneficial in PCOS.
  • Cosmetic and palliative treatments may be indicated in the treatment of many patients with insulin resistance syndrome, depending on the type and severity of physical anomalies (eg, epilation and electrolysis for hirsutism in patients with PCOS).

Consultations

  • Consultation with an endocrinologist is indicated in insulin resistance.
  • Consultation with a cardiologist is also indicated.
  • Other specialists, such as a dermatologist, gynecologist, cardiothoracic surgeon, and ophthalmologist, may need to be consulted based on the nature of the disease and the prevailing pathology.

Diet

  • Weight reduction improves insulin sensitivity in cases of obesity and in most of the obesity-related insulin-resistant states.
  • Restriction of caloric intake is indicated.

Activity

  • Exercise improves insulin sensitivity via the following20,21 :
    • Increased oxidative enzymes
    • Increased GLUT-4
    • Increased capillarity
    • Reduced central adiposity

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications. Medications that reduce insulin resistance include biguanides and thiazolidinediones, which have insulin-sensitizing and antihyperglycemic effects. Large quantities of insulin are also used in overcoming insulin resistance. Response to usual dosage of insulin is observed in instances in which the resistance is due to enhanced destruction at the subcutaneous injection site.

The treatment of type 2 diabetes and IGT—conditions that are strongly associated with insulin resistance and significant cardiovascular morbidity and mortality—should aim at restoring the normal relationship between insulin sensitivity and secretion. For diabetes, this involves pharmacotherapy, which includes stimulation of insulin secretion (sulfonylureas, meglitinides, incretin mimetics) and insulin sensitivity (metformin, thiazolidinediones), as well as treatment intended to support the signals that mediate the islet adaptation (incretin mimetics).22,23

Pramlintide (an amylin analogue) acts as an amylinomimetic agent by modulating gastric emptying, preventing postprandial increases in plasma glucagon, and promoting satiety, leading to decreased caloric intake and potential weight loss. Antiobesity drugs, such as orlistat and sibutramine, may reduce insulin resistance and related cardiovascular risk factors through weight reduction and other mechanisms. In most patients, the administration of insulin is also crucial in the treatment of diabetes.

Biguanides

Biguanides are insulin sensitizers useful in type 2 diabetes and related insulin resistance. They reduce hepatic glucose output and peripheral resistance to insulin action and lower plasma insulin levels.


Metformin (Glucophage)

Reduces hepatic glucose output, decreases intestinal absorption of glucose, and increases glucose uptake in the peripheral tissues (muscle and adipocytes). Major drug used in obese patients who have type 2 diabetes. Enhances weight reduction and improves lipid profile and vascular integrity. Individualize treatment with monotherapy or administer in combination with insulin or sulfonylureas.

Adult

Initial: 500 mg PO bid
Maintenance: 850 mg PO tid; not to exceed 2550 mg/d

Pediatric

Not established

Diuretics, thyroid products, oral contraceptives, phenytoin, calcium channel blocking drugs, and phenothiazines may decrease effects of metformin; cimetidine may increase metformin levels

Documented hypersensitivity; renal disease or impairment; ketoacidosis; acute myocardial infarction; septicemia; metabolic acidosis; receiving treatment for congestive heart failure (CHF); concomitant use of parenteral radiographic agents; type 1 diabetes

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Confirm normal renal function prior to starting therapy; caution in hepatic disease and elderly people; discontinue if lactic acidosis, hypoxemia, or sepsis occurs; discontinue therapy before performing any surgical procedures

Thiazolidinediones

These agents are insulin-sensitizing drugs that increase the disposal of glucose in peripheral tissues and act by activating a specific nuclear receptor, the peroxisome proliferator-activated receptor gamma (PPAR-gamma). Thiazolidinediones have a major effect in the stimulation of glucose uptake, skeletal muscle, and adipose tissue. They lower plasma insulin levels and are used to treat type 2 diabetes associated with insulin resistance. They appear to benefit patients with PCOS. Thiazolidinediones include rosiglitazone and pioglitazone.22,24
On May 21, 2007, following the online publication of a meta-analysis, the Food and Drug Administration (FDA) issued an alert to patients and health care professionals warning that rosiglitazone can potentially increase the risk for myocardial infarction and heart-related deaths. Rosiglitazone is an antidiabetic agent (thiazolidinedione derivative) that improves glycemic control by improving insulin sensitivity. The drug is highly selective and a potent agonist for PPAR-gamma. The activation of PPAR-gamma receptors regulates insulin-responsive gene transcription involved in glucose production, transport, and utilization, thereby lowering blood glucose concentrations and reducing hyperinsulinemia. Potent PPAR-gamma agonists have been shown to increase the incidence of edema. A large-scale, phase III trial (RECORD) is currently underway that is specifically designed to study cardiovascular outcomes of rosiglitazone.

For more information, see FDA's Safety Alert on Avandia. The meta-analysis, entitled Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes, can be viewed online. Additionally, responses to the controversy—including the articles Rosiglitazone increases MI and CV death in meta-analysis and The rosiglitazone aftermath: legitimate concerns or hype? —can be viewed at the Heartwire news site (the heart.org), from WebMD.


Pioglitazone (Actos)

May be used in monotherapy and in combination with metformin, insulin, or sulfonylureas. Improves target cell response to insulin without increasing insulin secretion from pancreas. Decreases hepatic glucose output and increases insulin-dependent glucose use in skeletal muscle and, possibly, in liver and adipose tissue.

Adult

15-30 mg/d PO; not to exceed 45 mg/d

Pediatric

Not established

May reduce plasma concentrations of contraceptives containing ethinyl estradiol and norethindrone; laboratory studies suggest ketoconazole may inhibit metabolism of pioglitazone (monitor blood glucose levels closely); pioglitazone in combination with insulin or oral hypoglycemics (eg, sulfonylureas) may increase risk for hypoglycemia

Documented hypersensitivity; active liver disease; ketoacidosis; type 1 diabetes

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor transaminases; discontinue if ALT rises above 3 times the upper limit of the reference range; caution in edema and CHF


Rosiglitazone (Avandia)

Insulin sensitizer with major effect in stimulation of glucose uptake in skeletal muscle and adipose tissue. Lowers plasma insulin levels. Used for treatment of type 2 diabetes associated with insulin resistance. May benefit PCOD patients. May use as monotherapy or in combination with metformin.

Adult

4-8 mg/d PO or divided bid

Pediatric

Not established

In combination with insulin or oral hypoglycemics (eg, sulfonylureas) may increase risk for hypoglycemia

Documented hypersensitivity; active liver disease; ketoacidosis; type 1 diabetes

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor transaminases; discontinue if ALT rises above 3 times the upper limit of the reference range; caution in edema and CHF; may decrease hemoglobin, hematocrit, and white blood cell counts

Glucocorticoids

These agents are immunosuppressants used for the treatment of immune insulin resistance due to anti-insulin antibodies.


Prednisone (Sterapred)

Immunosuppressant for the treatment of autoimmune disorders. May decrease inflammation by suppressing key steps of the immune reaction process.

Adult

80-100 mg/d PO initially; taper when insulin requirements begin to drop

Pediatric

Not established

Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections; GI disease

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hypothyroid state, peptic ulcer disease, tuberculosis, ocular herpes, hypertension, osteoporosis, and pituitary-adrenal axis suppression; avoid abrupt cessation of medication; supplement with additional steroid in stressful situations

Antidiabetic agent, insulin

This is used to overcome insulin resistance, but large quantities are often required.


Insulin (Humulin, Novolin, Humalog)

Stimulates proper utilization of glucose by the cells and reduces blood sugar levels. Various preparations are available.

Adult

Variable, usually 0.1-2.5 U/kg/d SC, but more than 200 U/d may be required

Pediatric

Administer as in adults

Hypoglycemic effect decreased by thyroid hormone, corticosteroids, estrogen, and thiazides; hypoglycemic effect increased by alcohol, anabolic steroids, salicylates, beta blockers, alpha blockers, and tetracycline

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Instruct patient on proper administration of insulin, blood testing, diet, exercise, and management of hypoglycemia; titrate dosage according to patient's need

Lipase inhibitors

These agents inhibit nutrient absorption.


Orlistat (Xenical)

Gastrointestinal lipase inhibitor that induces weight loss by inhibiting nutrient absorption. Effectiveness in producing weight loss does not depend on systemic absorption. May reduce absorption of some fat-soluble vitamins (A, D, E, K) and beta carotene. Administer multivitamin supplement containing fat-soluble vitamins PO qd 2 h ac or 1 h pc.

Adult

120 mg PO tid with ac (meals containing fat); may take up to 1 h pc

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Decreases absorption of vitamins A, D, K, acitretin, calcifediol, calcitriol, dihydrotachysterol, doxercalciferol, ergocalciferol, isotretinoin, tretinoin, and beta carotene; decreased vitamin K absorption may effect warfarin therapy; enhances effect of statin lipid-lowering agents; may decrease cyclosporine levels; may enhance hypoglycemic effect of sulfonylureas

Documented hypersensitivity; cholestasis; chronic malabsorption syndrome

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in organic causes of obesity (eg, hypothyroidism), rule out causes of obesity, other than dietary intake, prior to use; caution in patients with calcium oxalate nephrolithiasis or hyperoxaluria (increased levels of urinary oxalate may occur); potential for abuse by certain patients, including those with anorexia nervosa or bulimia nervosa

Anorexiants

These agents reduce appetite and may increase metabolism.


Sibutramine (Meridia)

Inhibits central reuptake of neurotransmitters (eg, dopamine, norepinephrine, serotonin). The pharmacologic action – inhibiting serotonin reuptake may produce enhanced satiety, while the action-inhibiting norepinephrine reuptake raises the metabolic rate.

Adult

10 mg/d PO; increase to 15 mg/d PO in 4 wk, if necessary; dose-response effect at 5-30 mg/d
5-mg dose reserved for patients who do not tolerate 10-mg dose

Pediatric

<16 years: Not established
>16 years: Administer as in adults

Metabolism inhibited by ketoconazole, cimetidine, erythromycin; increased risk for serotonin syndrome with MAOIs, SSRIs, sumatriptan, zolmitriptan, dihydroergotamine, dextromethorphan, meperidine, pentazocine, fentanyl, lithium, tryptophan, furazolidone, linezolid, and procarbazine; increased risk for cardiovascular complications with ephedrine, pseudoephedrine, and phenylpropanolamine (withdrawn from the US market)

Documented hypersensitivity; concomitant or within 2 wk of MAOI administration; concomitant use of centrally acting appetite suppressants; anorexia nervosa; poorly controlled hypertension; coronary artery disease; congestive heart failure; cardiac arrhythmias; stroke

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Prior to use, exclude organic causes of obesity (eg, untreated hypothyroidism); caution in patients with closed-angle glaucoma (causes mydriasis); caution in patients with seizure disorder (discontinue if seizures develop); precipitates or exacerbates gallstone formation; contributes to development of dental caries, periodontal disease, oral candidiasis, and discomfort; dose adjustment may be necessary in patients with renal/hepatic disease; schedule C-IV; use controlled substance cautiously in patients with history of substance abuse

More on Insulin Resistance

Overview: Insulin Resistance
Differential Diagnoses & Workup: Insulin Resistance
Treatment & Medication: Insulin Resistance
Follow-up: Insulin Resistance
References
Further Reading
[ CLOSE WINDOW ]

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Keywords

insulin resistance, diabetes insulin, metabolic syndrome, insulin resistant, fasting glucose, glucose tolerance, glucose tolerance test, type 2 diabetes mellitus, diabetes insulin resistance, insulin glucose, fasting insulin, insulin type 2 diabetes, insulin sensitivity, insulin resistance type, impaired fasting glucose, insulin-resistant state, glycemic control, ketosis, syndrome X, dysmetabolic syndrome, IFG, impaired glucose tolerance, IGT, type A syndrome, type B insulin resistance, obesity, glucose intolerance, diabetes, insulin-resistant state, polycystic ovary syndrome, PCOS, polycystic ovary disease, PCOD

Stein-Leventhal Syndrome, endothelial dysfunction, insulin receptor, insulinlike growth factor, IGF, tyrosine kinase, hyperinsulinemia, dyslipidemia, glucagonlike peptide-1, GLP-1, glucose transporter, GLUT, acanthosis nigricans, coronary artery disease, CAD, leprechaunism, lipodystrophic states, Werner syndrome, Werner’s syndrome, Rabson-Mendenhall syndrome, Rabson-Mendenhall’s syndrome, pineal hypertrophic syndrome, Alstrom syndrome, Alstrom’s syndrome, ataxia-telangiectasia, myotonic dystrophy, xanthelasma, xanthomata, hyperandrogenism

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Contributor Information and Disclosures

Author

Samuel T Olatunbosun, MD, FACP, Chief, Internal Medicine, 56th Medical Group, Luke Air Force Base
Samuel T Olatunbosun, MD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, and American Diabetes Association
Disclosure: Nothing to disclose.

Coauthor(s)

Samuel Dagogo-Jack, MD, MBBS, MSc, FRCP, Professor of Medicine, Program Director, Division of Endocrinology, Diabetes and Metabolism, University of Tennessee Health Science Center
Samuel Dagogo-Jack, MD, MBBS, MSc, FRCP is a member of the following medical societies: American College of Physicians, American Diabetes Association, American Federation for Medical Research, Endocrine Society, and Royal College of Physicians
Disclosure: Eli Lilly None Speaking and teaching; GlaxoSmithKline None Speaking and teaching; Merck None Speaking and teaching

Medical Editor

David S Schade, MD, Chief, Division of Endocrinology and Metabolism, Professor, Department of Internal Medicine, University of New Mexico School of Medicine and Health Sciences Center
David S Schade, MD is a member of the following medical societies: American College of Physicians, American Diabetes Association, American Federation for Medical Research, Endocrine Society, New Mexico Medical Society, New York Academy of Sciences, and Society for Experimental Biology and Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Don S Schalch, MD, Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, University of Wisconsin Hospitals and Clinics
Don S Schalch, MD is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, Central Society for Clinical Research, and Endocrine Society
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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