Severe Hyperglycemia Linked to Long-Acting HIV Treatment Cabotegravir/Rilpivirine

Recent reports indicate a potential link between the initiation of long-acting cabotegravir and rilpivirine (CAB/RIL) therapy and the development of severe hyperglycemia, including cases of diabetic ketoacidosis, in individuals with HIV. While previously not associated with metabolic outcomes, clinicians should now monitor blood glucose levels when starting this injectable treatment regimen.

What is CAB/RIL and Why is it Used?

Cabotegravir and rilpivirine are antiretroviral medications used to treat HIV. They are administered as an intramuscular injection, offering a long-acting treatment option compared to daily oral medications. This simplifies treatment for individuals who are virologically suppressed on oral antiretroviral therapy (ART) and are candidates for switching to a long-acting injectable regimen. HIV i-Base reports that patients often seek this option to simplify their treatment plans.

What are the Reported Cases?

The first published cases of this adverse effect appeared in the March 2026 issue of Diabetes &amp. Metabolism. Two men, aged 60 and 62, with a history of hypertension and well-controlled HIV, experienced severe hyperglycemia several weeks after switching from oral ART to injectable CAB/RIL.

• Case 1: Developed diabetic ketoacidosis (DKA) with a glucose level of 391 mg/dL and an HbA1c of 14.1%. Treatment involved intravenous insulin, followed by metformin. Glycemic control was achieved after switching back to a different ART regimen (TDF/FTC/doravirine).
• Case 2: Presented with a glucose level of 343 mg/dL and an HbA1c of 14.5%. This patient had a family history of type 2 diabetes and a low serum C-peptide level.

Both patients had normal glycemic values prior to starting CAB/RIL-based ART, though both had mildly increased values suggesting prediabetes in the year prior. Importantly, testing for pancreatic autoantibodies was negative in both cases, ruling out autoimmune diabetes. i-base.info provides detailed information on these cases.

What Does This Mean for Patients and Clinicians?

These are the first reported cases of severe hyperglycemia linked to CAB/RIL. The findings highlight the importance of monitoring blood glucose levels in patients initiating long-acting CAB/RIL therapy, even in those without a prior history of diabetes. Symptoms to watch for include increased thirst, frequent urination, and unexplained weight loss.

Key Takeaways

• Long-acting cabotegravir/rilpivirine (CAB/RIL) may be associated with severe hyperglycemia in some individuals.
• Clinicians should monitor blood glucose levels when initiating CAB/RIL therapy.
• Patients should be aware of the symptoms of hyperglycemia and report them promptly.
• Further research is needed to understand the mechanism behind this potential adverse effect and identify individuals at higher risk.

Current Understanding

As of February 28, 2026, neither diabetes nor hyperglycemia is listed as an adverse event in the official summary of product characteristics for cabotegravir and rilpivirine. This underscores the novelty of these findings and the need for ongoing vigilance.