Diabetes Drug Addresses Inflammation in HIV Patients

Sitagliptin appears to have beneficial systemic and adipose anti-inflammatory effects in combination antiretroviral therapy-treated HIV-positive adults with impaired glucose tolerance. The drug may prevent cardiovascular problems by reducing inflammation linked to heart disease and stroke in this patient population.

The diabetes drug sitagliptin (Januvia, Merk) appears to have beneficial systemic and adipose anti-inflammatory effects in combination antiretroviral therapy-treated HIV-positive adults with impaired glucose tolerance, according to a new study from researchers at Washington University School of Medicine in St. Louis. The study team suggests that the agent may prevent cardiovascular problems by reducing inflammation linked to heart disease and stroke in this patient population.

Patients living with HIV currently are substantially more likely to live relatively normal lives than they were 10 years ago. However, those with the virus are at greater risk for fasting hyperinsulinemia, impaired glucose tolerance, vascular disease, myocardial infarction, and stroke despite effective antiretroviral therapy. Chronic inflammation is thought to drive this risk.

The Washington University investigators found that sitagliptin improved both metabolism and inflammation in the study participants and published their findings in the May 4, 2015 online edition of TheJournal of Clinical Endocrinology & Metabolism.

“The goal has been to identify treatments that not only address problems with blood sugar and lipids but also can lower inflammation, which can play a substantial role in heart disease and stroke,” said principal investigator Kevin E. Yarasheski, PhD, Professor of Medicine, Cell Biology & Physiology, and Physical Therapy and Assistant Director or the Biomedical Mass Spectrometry Research Laboratory in the Division of Endocrinology, Metabolism and Lipid Research at Washington University School of Medicine. “With sitagliptin, sugar levels fell, and several markers of immune activation and inflammation were reduced, indicating the drug may provide long-term benefits for these patients' hearts, bones and livers.”

Although standard diabetes therapies have been shown in other studies to be somewhat successful in patients with HIV, they have not be found to completely normalize blood sugar, insulin and lipid levels, or other indicators of heart and metabolic health.

The current, 8-week study expands upon an earlier study of 20 patients with HIV that focused on whether sitagliptin was safe. To determine whether the agent provided specific health benefits, the team studied 36 patients with HIV who were aged 18 to 65 and whom had stable HIV disease and impaired glucose tolerance. At baseline, researchers measured participants’ glucose levels, insulin sensitivity, lipid levels, immune cell counts, several markers of inflammation, and other indicators of health. Patients were then randomized to sitagliptin or placebo for 8 weeks while continuing antiretroviral therapy.

“We wanted to know whether this drug would improve patients' blood-sugar problems and reduce the immune markers that we believe are indicators that something is activating the immune system and causing inflammation,” said Dr.Yarasheski. “And that's what we found.”

Large scale, long-term studies are need to determine whether lower markers of inflammation after 8 weeks of sitagliptin treatment can reduce cardiovascular risk and events in adults with HIV.

“Lowering blood sugar isn't enough,” said Dr. Yarasheski. “Just treating lipids isn't enough. We want to target the nexus between metabolic regulation and immune regulation. Whether this particular drug lowers inflammation enough to actually reduce cardiovascular disease, heart attack, stroke, and hypertension is a question that still needs to be addressed. But these findings are a step in the right direction.”