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Sitagliptin and HIV

Patients with HIV are not in immediate danger of death anymore. Instead, thanks to antiretroviral therapy, most relatively live normal lives for many years. However, the combination of HIV and the drugs used to treat it leads many HIV-positive patients to develop lipid problems, diabetes, obesity and cardiovascular disease. The search for treatments to fight those complications has led researchers at Washington University School of Medicine in St. Louis to a drug that improves insulin sensitivity and lowers inflammation in people with HIV. The researchers believe long-term use of the drug, called sitagliptin, may help combat the metabolic problems that affect people with the virus.

RESEARCHERS AT WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS HAVE FOUND THAT A DIABETES DRUG APPEARS TO LOWER CARDIOVASCULAR RISK AND MORE EFFECTIVELY TREAT GLUCOSE PROBLEMS IN PEOPLE WITH HIV. JIM DRYDEN REPORTS…

ALTHOUGH HIV IS NO LONGER RAPIDLY FATAL, PEOPLE INFECTED WITH THE VIRUS WHO TAKE ANTIRETROVIRAL THERAPY HAVE AN ELEVATED RISK FOR DIABETES AND CARDIOVASCULAR PROBLEMS. WASHINGTON UNIVERSITY RESEARCHER KEVIN YARASHESKI SAYS RESEARCHERS HAVE TRIED LOTS OF WAYS TO CONTROL THOSE COMPLICATIONS IN PEOPLE WITH HIV, FROM STANDARD DIABETES DRUGS TO DIET TO EXERCISE, AND HE SAYS ALL OF THOSE APPROACHES HAVE WORKED TO SOME DEGREE…

(act) :28 o/c lipid levels

But they don’t normalize lipid levels and sugar levels

and insulin levels, and so we’re thinking there’s

something else going on, other than just sugar problems

and lipid problems and obesity problems. And what

everybody seems to agree in the field is that, well no,

there’s something in their immune systems, something

that’s causing an inflammatory response or reaction in

their body that’s making them a little more resistant

to, sort of standard therapies that you would give for

diabetes or high lipid levels.

BECAUSE PEOPLE WITH HIV ALSO TEND TO HAVE CHRONIC INFLAMMATION, YARASHESKI SAYS EFFECTIVE TREATMENTS NEED TO ADDRESS THAT, TOO.

(act) :13 o/c the trick (2nd ref)

We need to do something to turn down inflammation in these

individuals. We think that that’s the underlying problem

that’s causing all of these cardio-metabolic complications.

So again, just treating their sugar isn’t going to do the

trick. Just treating their lipids isn’t going to do the trick.

THE IDEA, HE SAYS, IS TO TRY TO “KILL TWO BIRDS WITH ONE STONE,” AS IT WERE. HIS TEAM TESTED THE DIABETES DRUG SITAGLIPTIN IN 36 PEOPLE WHO HAD HIV AND HAD BLOOD SUGAR PROFILES SUGGESTING THEY WERE PREDIABETIC.

(act) :22 o/c be done

We readjusted their sugars down to lower levels — that’s

a good thing for blood sugar management – but we also reduced

several markers of immune activation and inflammation that we

think is going to have even a greater beneficial effect on other

parameters like their hearts, like their bones and like their

livers, but those studies, those efficacy studies, still need

to be done.

AND YARASHESKI SAYS HE HOPES SUCH LONG-TERM STUDIES MAY BEGIN RELATIVELY SOON, BOTH FOR SITAGLIPTIN AND FOR RELATED DRUGS THAT MAY BE ABLE TO AFFECT BOTH METABOLISM AND INFLAMMATION.

(act) :16 o/c good match

For now in my mind, sitagliptin is one of the few in its

class that will have this beneficial effect, simply because

it’s not metabolized by the liver. It’s relatively safe. It’s

cleared in the urine. So for HIV, it’s a good match.

AND HE SAYS EFFECTIVE LONG-TERM THERAPIES FOR HIV-RELATED METABOLIC AND CARDIOVASCULAR PROBLEMS ARE NEEDED BECAUSE HIV ISN’T GOING ANYWHERE.

(act) :24 o/c complications now

And there will always be a need to do something to treat

not only these metabolic complications but also the immune

disregulation that goes on in an HIV-infected individual

that, again, we believe go hand-in-hand with the metabolic

complications. So it’s very hard to separate the two, but

if you have a drug that treat’s both, you’re one step

closer to a more effective treatment than what we have for

the complications now.

YARASHESKI’S TEAM REPORTED ITS FINDINGS IN THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. I’M JIM DRYDEN…

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