What medications are associated with drug-induced metabolic disorders?

From the Guidelines

Medications such as glucocorticoids, statins, thiazide diuretics, some HIV medications, and second-generation antipsychotic medications are associated with an increased risk of drug-induced metabolic disorders, including hyperglycemia, dyslipidemia, and weight gain, and should be considered when deciding whether to screen for prediabetes or diabetes 1.

Medications Associated with Metabolic Disorders

• Glucocorticoids, such as prednisone and dexamethasone, can cause hyperglycemia, weight gain, and dyslipidemia through insulin resistance and altered fat metabolism.
• Statins, particularly those metabolized by the CYP3A4 or CYP2C9 enzymes, can increase the risk of hyperglycemia and dyslipidemia.
• Thiazide diuretics, such as hydrochlorothiazide, can cause hyperglycemia, hypokalemia, and hyperuricemia.
• Some HIV medications, such as protease inhibitors, can cause lipodystrophy and insulin resistance.
• Second-generation antipsychotic medications, particularly olanzapine, clozapine, and quetiapine, can cause weight gain, diabetes, and dyslipidemia by affecting insulin sensitivity and appetite regulation.

Monitoring and Management

Patients taking these medications should receive regular metabolic monitoring, including glucose levels, lipid panels, and electrolytes, to balance the risk of metabolic complications against the therapeutic benefits of these medications 1. Alternative treatments with lower metabolic risk profiles may be considered for susceptible patients. For example, people taking second-generation antipsychotic medications should be screened for prediabetes or diabetes at baseline, re-screened 12–16 weeks after medication initiation, and screened annually thereafter 1.

From the FDA Drug Label

Atypical antipsychotic drugs have been associated with metabolic changes including hyperglycemia, dyslipidemia, and weight gain. Hyperglycemia and Diabetes Mellitus: In some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients taking olanzapine. Dyslipidemia: Undesirable alterations in lipids have been observed. Weight Gain: Potential consequences of weight gain should be considered.

The medications associated with drug-induced metabolic disorders are atypical antipsychotic drugs, such as olanzapine. These medications have been linked to:

• Hyperglycemia
• Dyslipidemia
• Weight gain 2

From the Research

Medications Associated with Drug-Induced Metabolic Disorders

The following medications have been linked to drug-induced metabolic disorders:

• Antipsychotic medications, such as:
  • Olanzapine 3, 4, 5, 6
  • Clozapine 4, 5, 6
  • Risperidone 6
  • Quetiapine 6
• Glucocorticoids (GC) 7
• Typical antipsychotics, such as:
  • Haloperidol 6
  • Fluphenazine 6

Specific Metabolic Effects

These medications have been associated with various metabolic effects, including:

• Hyperglycemia 3, 4, 5, 7, 6
• Hyperinsulinemia 4, 5
• Hyperlipidemia 4, 5, 7, 6
• Insulin resistance 4, 7
• Weight gain 6
• Diabetic ketoacidosis 3, 7

Mechanisms of Action

The mechanisms by which these medications induce metabolic disorders are complex and multifactorial, involving:

• Decreased peripheral insulin sensitivity 7
• Increased hepatic glucose production 7
• Inhibition of pancreatic insulin production and secretion 7
• Transcriptional changes in metabolically active peripheral tissues 5