How is dolutegravir-induced hyperglycemia managed in patients with HIV?

Management of Dolutegravir-Induced Hyperglycemia in HIV Patients

For patients experiencing dolutegravir-induced hyperglycemia, lifestyle modifications, exercise, and dietary interventions are recommended as first-line management while continuing the dolutegravir-based regimen, with oral hypoglycemic agents or insulin added if necessary for glycemic control. 1

Monitoring and Detection

• Monitor blood glucose levels in all patients starting dolutegravir, especially those with pre-existing risk factors for diabetes 2
• Routine fasting blood glucose measurements should be performed at 3-4 month intervals during the first year of treatment 1
• Time to onset of hyperglycemia typically ranges from 2-5 months after initiation of dolutegravir 3
• Be vigilant for warning signs of hyperglycemia (polydipsia, polyphagia, polyuria) and educate patients about these symptoms 1
• Glucose tolerance tests are not recommended for routine screening (DIII recommendation) 1

Management Approach

For New-Onset Hyperglycemia/Diabetes

1. Continue dolutegravir-based regimen in the absence of severe diabetes (BIII recommendation) 1

   • Changing regimens due to hyperglycemia or insulin resistance is not recommended (BIII recommendation) 1

2. Implement lifestyle interventions as first-line management:

   • Dietary modifications 1
   • Regular exercise 1
   • Weight management to maintain recommended body weight 1

3. Pharmacological management when needed:

   • Oral hypoglycemic agents (e.g., metformin) for mild to moderate hyperglycemia 3, 4
   • Insulin therapy for severe hyperglycemia or diabetic ketoacidosis 3, 5

For Severe Hyperglycemia or Diabetic Ketoacidosis

• Acute management with intravenous fluids and insulin therapy 4, 5
• After stabilization, transition to oral hypoglycemic agents when appropriate 4, 5
• Continue close monitoring of blood glucose levels 3, 4

Special Considerations

• Pregnant women require closer monitoring of blood glucose levels due to pregnancy being an independent risk factor for impaired glucose tolerance 1
• Patients with pre-existing diabetes should have more intensive monitoring when starting dolutegravir 1
• In a community health center study, 83% of patients with pre-existing diabetes required intensification of their diabetes regimen after starting dolutegravir 2

Clinical Outcomes and Prognosis

• Approximately 7% of patients may develop prediabetes within 3-6 months of dolutegravir initiation 2
• By the end of longer follow-up periods, up to 13% may develop prediabetes and 1.4% may develop diabetes 2
• Most patients can achieve good glycemic control with standard diabetes management while continuing dolutegravir 4, 5
• The long-term reversibility of dolutegravir-induced hyperglycemia is not well established 1

Risk Factors to Consider

• Older age (>40 years) 4
• Longer duration of HIV infection 1
• Previous antiretroviral therapy experience 6
• Weight changes after starting dolutegravir 6

While hyperglycemia is a recognized side effect of dolutegravir, the current evidence supports continuing the medication with appropriate diabetes management rather than switching antiretroviral regimens in most cases.