Sleepyman,
Over the past few months there have been reports in the Medscape Endocrinology newsletter of newly
discovered side effects from the second generation glitazones. Macular Edema and congestive heart
failure were the major ones.
Thiazolidinediones Contraindicated in Patients at Risk for Heart Failure CME
News Author: Laurie Barclay, MD CME Author: Charles Vega, MD Authors and Disclosures
To earn CME credit, read the news brief, the paragraphs that follow, and answer the questions below.
Release Date: December 8, 2003; Valid for credit through December 8, 2004
Credits Available
Physicians - up to 0.25 AMA PRA category 1 credit(s)
Dec. 8, 2003 - A joint statement from the American Heart Association (AHA) and the American Diabetes
Association (ADA), published in the Dec. 9 issue of Circulation, urges physicians not to prescribe
thiazolidinediones (TZDs) to patients at risk for congestive heart failure (CHF). The statement will
also be published in the January 2004 issue of Diabetes Care.
"There is now widespread use of TZDs in a broad group of patients with type 2 diabetes," lead author
Richard W. Nesto, MD, from the Lahey Clinic in Burlington, Massachusetts, says in a news release.
"At the same time there have been reports of CHF associated with their use."
The TZDs rosiglitazone maleate (Avandia) and pioglitazone hydrochloride (Actos) are indicated as
monotherapy or as combination therapy for type 2 diabetes. Although these drugs help control blood
glucose and may improve other cardiovascular risk factors including hypertension, high cholesterol,
and inflammatory biomarkers, some patients treated with these drugs develop edema.
"It is sometimes difficult to know whether such swelling is a benign side effect of the drugs or a
more ominous sign of heart failure," Dr. Nesto says. "It is this common association that concerns
both cardiologists and diabetologists."
To balance improved glycemic control achieved with TZDs against potential risk, the joint statement
writing committee reviewed existing trials to identify diabetic patients who are at increased risk
for CHF and who may not be ideal candidates for TZDs.
Recommendations of the consensus statement include avoidance of TZDs in patients with advanced heart
disease or severe CHF. In patients with depressed ejection fraction but without symptoms of CHF,
TZDs should be prescribed only if glycemic control cannot be achieved with other drugs, and in these
cases TZDs should be started at low doses.
The statement also recommends a "start low, go slow" regimen of TZDs for diabetics with mild to
moderate CHF, and in those with one or more risk factors for CHF. Because diabetes is a
cardiovascular risk factor, many patients given TZDs for diabetes could also have underlying
heart disease.
"But at this point we don't know the real risk because we don't know either the actual number of
patients with diabetes who are taking a TZD and develop CHF, compared to the total number of
patients who are taking a TZD," Dr. Nesto says. "This risk is probably quite low, but without solid
data that's just guesswork."
According to the statement, patients receiving TZD treatment should report weight gain of more than
3 kg (6.6 lb), sudden onset of pedal edema, dyspnea, or fatigue. For CHF diagnosed after initiation
of TZD therapy, "dosage change and temporary or permanent discontinuance are the obvious options,
but no one of these is preferred for all patients," the authors write.
Circulation. 2003;108:2941-2948
======
Glitazone Use May Be Associated With Macular Edema in Diabetics
Karla Harby
Nov. 19, 2003 (Anaheim) - Results of a retrospective chart view suggest that glitazone use may be
linked to the existence of macular edema in patients with diabetes, according to a study presented
here at the annual meeting of the American Academy of Ophthalmology.
Whether glitazones aggravate existing macular edema, or tend to be prescribed for patients who would
have developed the condition anyway, or actually cause macular edema, cannot be determined from a
retrospective study. But fluid retention is a recognized adverse effect of glitazone therapy and a
known problem in the management of macular edema.
Edwin Hurlbut Ryan, Jr., MD, who presented the study, said the review involved 30 patients seen over
the past four years in his specialty referral practice in Du Bois, Pennsylvania.
During an interview with Medscape, the discussant for the paper, Justin L. Gottlieb, MD, from the
University of Wisconsin at Madison, noted that despite the limitations of this study, he now
recommends that ophthalmologists question the use of glitazones in patients with macular edema.
There are other ways to control diabetes besides administering glitazones, he pointed out.
Physicians are already warned in the package inserts about using glitazones in patients with certain
other conditions, such as congestive heart failure. "I think that's what this should be, a warning,
so people are aware of it,"
Dr. Gottlieb said.
Ds. Ryan identified his study group through a computer search of records for the brand names Actos
(pioglitazone) and Avandia (rosiglitazone). To be included, patients had to have clinically
significant macular edema in at least one eye and lower extremity edema associated with
glitazone use.
The study cohort involved 19 men and 11 women with an average age of 61. Seventeen patients were
taking pioglitazone, 11 were taking rosiglitazone, and two took both medications sequentially. Two
patients received glitazones as monotherapy, 12 received other oral agents in addition to
glitazones, seven received insulin alone with glitazones, seven received insulin plus oral agents
and glitazones, and for two patients these data were unavailable.
"All had pitting lower extremity edema, and in some cases it was quite severe," said Dr. Ryan.
Average weight gain after initiation of glitazone therapy was 33 pounds. All 30 patients had macular
edema, and 23 had bilateral disease. The average visual acuity at initial visit was 20/50.
Ten patients were followed for more than three months after glitazones were discontinued, with an
average follow-up of 10 months. "Patients and primary doctors were very reluctant to discontinue the
drugs because of the good glycemic control they finally achieved," Dr. Ryan noted.
Once the drugs were discontinued, patients experienced rapid reduction in lower extremity edema,
usually returning to baseline in about two to three months, Dr. Ryan said. The weight lost after
stopping glitazone therapy averaged 19 pounds. "Several patients reported improved exercise
tolerance off the drugs," Dr. Ryan added.
Dt. Ryan observed a reduction of macular edema in less than three months in only three of 10
patients, but eventually observed a reduced degree of macular edema in seven of 10 patients over
a one- to two-year period. The three patients who showed no decrease in macular edema had
discontinued glitazone treatment for less than three months. Three eyes experienced a reduction
in macular edema with no laser treatment.
The average visual acuity at initial visit among these 10 patients was
20/70, and at the most recent visit, the average was 20/90. "While most patients had a decrease in
macular edema over time, visual improvement was not necessarily seen," Dr. Ryan noted.
"The authors are to be commended for recognizing a potentially important cause of macular edema and
visual loss, " said Dr. Gottlieb, whose search of the medical literature failed to uncover any
previous reports associating glitazone use with macular edema.
Du. Gottlieb pointed out that 50 of 60 eyes underwent laser photocoagulation for macular edema, and
24 eyes underwent multiple sessions. But "the edema was unusually resistant to treatment and
visual outcomes were poor despite control of fluid retention," he said. "Of note, only one
patient experienced spontaneous resolution of macular edema with cessation of drug and
resolution of fluid retention."
Because the study was retrospective, it is not possible to deduce cause and effect, Dr. Gottlieb
told the audience. "Despite the weaknesses, the association between fluid retention and macular
edema is a logical one," he said. "We are aware of other causes of fluid retention that worsen
macular edema. Treatment of these patients requires control of the medical disease as well as laser
intervention."
This study was independently funded. The speakers reported no pertinent financial disclosures.
AAO 2003 Annual Meeting: Free Papers. Presented Nov. 18, 2003.
Reviewed by Gary D. Vogin, MD
Karla Harby is a freelance writer for Medscape.
-- Jenny - Low Carbing for 4 years. At goal for weight. Type 2 diabetes, hba1c 5.2. Cut the carbs
to respond to my email address!
Low carb facts and figures, my weight-loss photos, tips, recipes, strategies for dealing with
diabetes and more at geocities.comjenny the beanOpen ↗
Looking for help controlling your blood sugar? Visit alt-support-alt-support-Open ↗
diabetes.org/Newly%20Diagnosed.htm
"Sleepyman" <[email hidden]> wrote in message "]news:[email hidden]...
Quoted message said:On Sat, 17 Jan 2004 11:09:59 -0500, "Jenny" <[email hidden]> wrote:
<snip>
Quoted message said:Actos is very new and its dangerous side effects are only gradually
coming
Quoted message said:Quoted message said:to light. -- Jenny -
If they are coming to light, show me that light.
SM
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Let's Kick the Right Wing, Out of the West Wing
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