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Januvia may prevent heart disease in HIV patients
The antidiabetic drug Januvia demonstrated beneficial systemic and adipose anti-inflammatory effects in HIV-infected adults with impaired glucose tolerance, according to research published in the Journal of Clinical Endocrinology andMetabolism.
“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,” Kevin E. Yarasheski, PhD, professor of medicine at Washington University School of Medicine, said in a press release. “With [Januvia (sitagliptin, Merck)], 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.”
Yarasheski and colleagues conducted a randomized, placebo-controlled, double blind study of 36 men and women with HIV, aged 18 to 65 years, who had received combination ART (cART) for the past 6 months and whose immune and virologic statuses were stable. None of the patients had type 2 diabetes or were taking antidiabetes medications, nor did they have an AIDS-defining diagnosis, history of heart failure, chronic kidney or liver dysfunction, pancreatitis, or active malignancy, according to the researchers.
Participants were given either 100 mg sitagliptin daily or placebo for 8 weeks.
“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,” Yarasheski said in the release. “And that’s what we found.”
According to Yarasheski and colleagues, both glucose area under the curve (P = .002) and oral glucose insulin sensitivity index (P = .04) improved more in patients assigned sitagliptin compared with controls. At 8 weeks, those who received sitagliptin experienced a decrease in plasma high-sensitivity C-reactive protein (hsCRP) and CXCL10 (P ≤ .008) — both discriminative markers for inflammation, particularly in cART-treated HIV patients. This was in sharp contrast to the placebo group, which saw an increase in hsCRP. In addition, in terms of immune regulation, adipose tissue monocyte chemoattractant protein-1 mRNA abundance declined more in patients receiving sitagliptin (P = .01), and epidermal growth factor-like module containing mucin-like hormone receptor 1 mRNA abundance tended to decline more in the treatment arm as well, although this was not statistically significant.
“Larger, longer-term studies are required, but these findings suggest that Januvia provides several beneficial pleiotropic and anti-inflammatory actions that may reduce diabetes and cardiovascular disease risk factors in HIV-infected adults who are taking their anti-retroviral medications, have undetectable plasma viremia, greater than 300 CD4+ T-cells/µL, [and] yet are still at risk for complications associated with residual immune cell activation,” Yarasheski told Infectious Disease News. – by David Jwanier
Disclosure: Yarasheski reports receiving grant support and product from Merck.
Perspective
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These findings are encouraging that sitagliptin caused significant reductions in some inflammatory markers in patients with HIV and glucose intolerance. It should be noted, however, that not all inflammatory markers associated with non-AIDS–related clinical endpoints were reduced in the patients treated with sitagliptin including IL-6 and d-dimer.
Furthermore, soluble CD14 levels, which are thought to be a marker of microbial translocation, inexplicably decreased in the placebo group while they increased slightly in the sitagliptin group. Thus, it is premature to conclude that sitagliptin will decrease non-AIDS–related clinical endpoints because of its anti-inflammatory properties. The researchers were appropriately cautious about interpreting the findings of their study. Their data provide important justification to conduct a clinical endpoint study to determine the effects of sitagliptin on non-AIDS–defining morbidity and mortality.