Two cases of severe hyperglycemia with injectable CAB/RPV-LA

Two cases of severe hyperglycemia have been reported several weeks after switching from stable oral ART to injectable long-acting cabotegravir/rilpivirine.

This is the first time this has been reported and the cases were published in the March 2026 issue of the journal Diabetes & Metabolism. [1]

Both cases were men aged 60 and 62, with a history of hypertension, but with good CD4 counts on ART and viral load >30 copies/mL who wanted to simplify treatment by switching. Both presented with lethargy, frequent urination, and polydipsia (high thirst) and 5 kg wright loss. nmol/L). Both patients had normal glycemic values before starting CAR-LA-based ART but both presented in the preceding year with mildly increased glycemic values suggesting a prediabetic condition. Pancreatic autoantibodies (anti-IA2, anti-GAD and anti-ZnT8) were negative in both cases.

One case presented (after two months on CAB/RPV/LA) with “diabetic ketoacidosis (DKA) and severe hyperglycemia: glucose 391 mg/dl HbA1c 14.1 % metabolic acidosis (pH: 7.36, serum bicarbonate: 17.6 mEq/l) and urine ketones (4+). His glycemic level was 101 mg/dL and he had no family history of diabetes. His BMI was 27 kg/m2.”

“He was immediately treated with intravenous insulin. Slow-acting insulin (26 UI) and rapid-acting insulin (6/8/7 UI) were initiated and later changed to metformin 500 mg twice a day then three times a day 4 days after admission. The CAR-LA regimen was switched to TDF/FTC/doravirine. After 3 months he achieved good glycemic control (HbA1c: 6.6 %) on metformin alone.”

The second case presented after five months on CAB/RPV-LA. “His glycemic value was 343 mg/dl HbA1c 14.5 % and urine glucose 3+ with no ketone bodies. He had a family history of type 2 diabetes mellitus (his sister). Serum C-peptide level was low 0.29 nmol/L (N 0.4–1.7). His BMI was 34.6 kg/m2.”

“He was treated with intravenous insulin. Slow-acting (25UI) and rapid-acting insulins were initiated later changed to metformin 1000 mg twice a day and diamicron 120 mg 4 days after admission. Good glycemic control (glycemia: 81 mg/dl, HbA1c: 6.4 %) was obtained 3 months later with metformin while the INSTI-based ART regimen was continued.”

The authors noted that neither diabetes nor hyperglycemia is listed as an adverse event in the SPC for either cabotegravir or rilpivirine but they found an additional five reported cases in a literature search.

They suggested that both cases might have been prediabetic and that closely monitoring glucose could be important in people with even mildly increased glycemia or with a high BMI.

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Please refer to the full details of these cases online which are only summarised here as this paper is open access.

These cases also perhaps show the importance of unexplained weight loss as a significant symptom thatwarrants further investigations.

Valin N et al. Severe hyperglycemia after initiation of long-acting cabotegravir in two antiretroviral treatment-controlled people with HIV. Diabetes & Metabolism 52(2), March 2026.
https://doi.org/10.1016/j.diabet.2026.101744