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

Management of Dolutegravir-Induced Hyperglycemia in HIV Patients

Lifestyle modifications, exercise, and diet intervention are recommended as first-line management for dolutegravir-induced hyperglycemia, while continuing the antiretroviral therapy regimen in the absence of severe diabetes (evidence rating: AIII). 1

Epidemiology and Risk Assessment

Dolutegravir (DTG), an integrase strand transfer inhibitor (InSTI), has been associated with hyperglycemia and new-onset diabetes in multiple studies:

• Incidence of hyperglycemia in patients on InSTI-based regimens is reported in some cohort studies, though data remain inconclusive 1
• In community health center settings, approximately 7% of patients developed prediabetes within 3-6 months of starting dolutegravir, with 13% developing prediabetes by the end of study period 2
• Time to onset of hyperglycemia typically ranges from 2-5 months after initiation of dolutegravir 3

Monitoring Recommendations

• Monitor blood glucose levels at each clinical visit for patients on dolutegravir-based regimens 1
• For patients without previous history of diabetes, routine fasting blood glucose measurements at 3-4 month intervals during the first year of treatment is recommended (CIII) 1
• Closer monitoring is warranted for:
  • Patients with pre-existing diabetes
  • Pregnant women (pregnancy is an independent risk factor for impaired glucose tolerance)
  • Patients with other risk factors for diabetes

Management Algorithm

1. Initial Detection of Hyperglycemia

   • Confirm hyperglycemia with repeat testing
   • Assess for symptoms of hyperglycemia (polydipsia, polyphagia, polyuria) 1
   • Evaluate severity of hyperglycemia

2. For Mild to Moderate Hyperglycemia (Prediabetes or Non-Severe Diabetes)

   • Implement lifestyle modifications:
     • Diet intervention with reduced carbohydrate intake
     • Regular exercise regimen
     • Weight management 1
   • Continue dolutegravir-based ART regimen (BIII) 1
   • Monitor blood glucose regularly

3. For Severe Hyperglycemia or Diabetic Ketoacidosis

   • Hospitalize for acute management if necessary
   • Administer IV fluids and insulin as appropriate for diabetic ketoacidosis 4, 5
   • Consider oral hypoglycemic agents or insulin for ongoing management 3
   • Continue dolutegravir-based ART in most cases (BIII) 1

Important Clinical Considerations

• The majority of experienced clinicians recommend continuation of HAART in the absence of severe diabetes (BIII) 1
• Changing regimens due to insulin resistance is not recommended (BIII) 1
• Routine use of glucose tolerance tests to detect this complication is not recommended (DIII) 1
• Among patients with pre-existing diabetes, 83% may require intensification of their diabetes regimen after starting dolutegravir 2

Pitfalls and Caveats

• Do not automatically discontinue dolutegravir in all patients who develop diabetes, as this may not be necessary in all cases 6
• Be aware that symptoms of hyperglycemia may appear at a median of approximately 60 days (range: 2-390 days) after initiation of therapy 1
• Some patients may develop diabetic ketoacidosis, requiring more aggressive management 4, 5
• Weight gain associated with dolutegravir may contribute to metabolic complications including hyperglycemia 1
• The reversibility of hyperglycemia after discontinuation of dolutegravir is not well established due to limited data 1

By following these recommendations, clinicians can effectively manage dolutegravir-induced hyperglycemia while maintaining effective HIV treatment for most patients.