Liraglutide treatment in a patient with HIV and uncontrolled insulin-treated type 2 diabetes.

Combination antiretroviral therapy has improved survival in human immunodeficiency virus (HIV)-infected patients but has become associated with altered body fat distribution, type 2 diabetes, and increased cardiovascular risk (1). Both the protease inhibitors and nucleotide reverse transcriptase inhibitors have been implicated (1). Management of HIV-associated type 2 diabetes may be challenging because of severe insulin resistance, which—in spite of the initial use of insulin sensitizers—often requires a high dose of insulin, causing additional weight gain (1). The glucagon-like peptide-1 receptor agonists lower glucose, reduce weight, and improve the cardiovascular risk profile in type 2 diabetes (2,3). Recently, exenatide use in an HIV-associated type 2 diabetic case and in a type 1 diabetic HIV patient was reported (4,5). Here, we report the first successful liraglutide use in an HIV patient with type 2 diabetes.

A 57-year-old man regularly visited the outpatient clinic since 2003 because of an HIV infection, which was diagnosed in 1995. Initial treatment consisted of zidovudine, then dual-therapy zidovudine and zalcitabine. From 1997–2003 he received zidovudine and lamivudine, then triple-therapy with efavirenz, didanosine, and lamivudine, which was discontinued because of dizziness, rash, and depression. Then, atazanavir, tenofovir, and lamivudine were given. In 2005, because of a progressive abdominal distention, the protease inhibitor atazanavir was replaced by raltegravir, an integrase inhibitor with a better metabolic profile.

In 2005, at a weight of 105 kg, compatible with a 15-kg weight gain in 2 years, type 2 diabetes was diagnosed. After lifestyle consultation, metformin (1,000 mg b.i.d.) was initiated. Since A1C rose to 8.8%, NPH insulin was started (November 2007). Body weight increased by 5 kg in 6 months with little glycemic improvement. Insulin treatment was replaced by glimepiride (up to 6 mg q.i.d.), but A1C remained 8.3%. He could be persuaded to start insulin glargine (September 2010), titrated to 60 U/day, while glimepiride was discontinued. Unfortunately, weight increased by 7 kg in 6 months without glycemic improvement. In May 2011, at a weight of 116 kg (BMI 35.1 kg/m2) and A1C 8.1%, off-label liraglutide was initiated at 0.6 mg/day, and uptitrated to 1.8 mg/day. He consulted a dietitian and diabetes educator and was advised to lower daily insulin dose by 10 U when self-monitored blood glucose was <5 mmol/L. After 3 weeks of liraglutide therapy, body weight dropped to 110 kg, insulin dose was reduced to 30 U/day, and discontinued altogether after 6 weeks. Fasting glucose decreased from 12.3 to 7.0 mmol/L. The patient reported no side-effects or hypoglycemia, rather less fatigue and overall improved quality of life. Self-monitored blood glucose varied between 5.6–8.3 mmol/L, HIV-RNA remained undetectable. Four months after liraglutide initiation, A1C decreased to 6.8% and body weight to 102 kg, but body weight rose slightly to 108 kg at 7 months, while A1C remained 6.8%. Previously elevated liver enzymes normalized while his lipid profile improved significantly (total cholesterol from 5.6 to 4.9 mmol/L, HDL cholesterol from 0.79 to 1.0 mmol/L, triglycerides from 6.6 to 3.1 mmol/L). This case illustrates that glucagon-like peptide-1 receptor agonists, possibly by improving weight control, body fat distribution, and cardiovascular markers (3), may be a valuable tool in the treatment of HIV-associated type 2 diabetes, which is characterized by central obesity, lipodystrophy, and insulin resistance.