Thiazolidinediones Contraindicated in Patients at Risk for Heart Failure CME

News Author: Laurie Barclay, MD
CME Author: Charles Vega, MD
Authors and Disclosures

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

Learning Objectives
Upon completion of this activity, participants will be able to:
List the nonhypoglycemic benefits of TZDs.
Describe how TZDs should and should not be used in the presence of CHF and CHF risk factors.
Clinical Context
TZDs have emerged as a treatment option for patients with diabetes in part due to effects beyond
their ability to lower serum glucose. In a review by Parulkar and colleagues appearing in the Jan.
2, 2001, issue of the Annals of Internal Medicine, the authors cite reduced blood pressure,
correction of diabetic dyslipidemia, improvement in fibrinolysis, and a decrease in carotid artery
intima-media thickness as other benefits associated with TZDs. However, the authors tempered their
enthusiasm for TZDs in a discussion of the weight gain associated with the drugs.

Weight gain and fluid retention are known adverse events associated with TZD use. In a retrospective
analysis by Tang and colleagues of diabetic patients with known heart failure using TZDs, 17.1% of
subjects developed fluid retention that resolved after the TZD was discontinued. The research, which
appeared in the April 16, 2003, issue of the Journal of the American College of Cardiology,
demonstrated that female sex and insulin use predisposed patients to weight gain with TZDs.

To reconcile the risks and benefits of TZDs in diabetic patients who either currently have CHF or
have significant CHF risk factors, the AHA and ADA released the current consensus statement based on
available evidence.

Study Highlights
Weight gain is common with both rosiglitazone and pioglitazone and may be due to both increased
caloric retention as well as fluid retention. When combined with a sulfonylurea, weight gain may
vary between 1.8 to 2.9 kg. Weight gain is even more significant when TZDs are combined with insulin
(average gain, 2.3 - 5.4 kg).
Edema is also frequently found in patients taking TZDs, occurring in 3% to 5% of patients using TZDs
as monotherapy. Rates of edema are higher if TZDs are used in combination with other hypoglycemic
agents. 13.1% to 16.2% of patients taking TZDs with insulin may experience edema.
CHF is not frequently encountered with TZD use. Rosiglitazone, either alone or in combination with
other oral hypoglycemic agents, is associated with an incidence of CHF of less than 1%. However, CHF
incidence rises to 2% to 3% if rosiglitazone is combined with insulin. Pioglitazone has been
associated with an incidence of CHF of 1.1%.
In reviewing case reports of CHF associated with the use of TZDs, the authors of the consensus
statement caution that TZDs may unmask previously asymptomatic cardiac insufficiency by increasing
plasma volume.
The recommendations of the consensus panel are as follows:
Before prescribing a TZD, the physician should perform a thorough history and physical for risk
factors, such as previous myocardial infarction or significant valvular disease, that could
predispose a patient to CHF. Baseline dyspnea and edema should be recorded.
Physicians should also pay attention to other medications, such as vasodilators, which may also
contribute to fluid retention.
Peripheral edema is not a contraindication for TZD use, but it should be monitored during TZD
therapy.
Patients should be instructed to report any weight gain more than 3 kg, new pedal edema, dyspnea, or
fatigue after starting a TZD.
In patients without known heart disease but with 1 or more cardiac risk factors, TZDs should be
started at the lowest possible dose and advanced cautiously with special attention to possible fluid
overload.
TZDs should be avoided if possible when the patient has a known reduced ejection fraction (<40%) but
is asymptomatic. Again, if TZDs must be used, the patient should be started on the lowest possible
dose and advanced cautiously.
TZDs also may be used with close patient supervision if the patient has known class I or II New York
Heart Heart Association (NYHA) CHF.
TZDs should be avoided in cases of class III or IV NYHA CHF.
If evidence of fluid overload manifests itself during TZD therapy, especially in the first few
months of treatment, the physician should mount a thorough investigation for CHF. This should
include an electrocardiogram, echocardiogram, and, possibly, serum evaluation for brain natriuretic
peptide.
If CHF is not present in a patient receiving TZDs with evidence of fluid overload, other drugs that
may contribute to increased intravascular volume should be reconsidered. The TZD also may be
discontinued or modified to a lower dose. Angiotensin-converting enzyme inhibitors with or without a
thiazide diuretic may help to reduce edema.
Any treatment-emergent CHF should prompt a reconsideration of the use of a TZD. If the TZD is
discontinued, symptoms of volume overload should be expected to resolve fairly quickly, and diuretic
therapy may be needed for only a short time.
Pearls for Practice
TZDs offer diabetic patients benefits beyond lowering serum glucose.
TZDs frequently lead to fluid retention. All patients receiving TZDs should be monitored for
symptoms and signs of fluid retention. TZDs should be avoided in patients with moderate to severe
CHF or evidence of an ejection fraction less than 40%.

Thiazolidinediones Contraindicated in Patients at Risk for Heart Failure CME

News Author: Laurie Barclay, MD
CME Author: Charles Vega, MD
Authors and Disclosures

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

Learning Objectives
Upon completion of this activity, participants will be able to:
List the nonhypoglycemic benefits of TZDs.
Describe how TZDs should and should not be used in the presence of CHF and CHF risk factors.
Clinical Context
TZDs have emerged as a treatment option for patients with diabetes in part due to effects beyond
their ability to lower serum glucose. In a review by Parulkar and colleagues appearing in the Jan.
2, 2001, issue of the Annals of Internal Medicine, the authors cite reduced blood pressure,
correction of diabetic dyslipidemia, improvement in fibrinolysis, and a decrease in carotid artery
intima-media thickness as other benefits associated with TZDs. However, the authors tempered their
enthusiasm for TZDs in a discussion of the weight gain associated with the drugs.

Weight gain and fluid retention are known adverse events associated with TZD use. In a retrospective
analysis by Tang and colleagues of diabetic patients with known heart failure using TZDs, 17.1% of
subjects developed fluid retention that resolved after the TZD was discontinued. The research, which
appeared in the April 16, 2003, issue of the Journal of the American College of Cardiology,
demonstrated that female sex and insulin use predisposed patients to weight gain with TZDs.

To reconcile the risks and benefits of TZDs in diabetic patients who either currently have CHF or
have significant CHF risk factors, the AHA and ADA released the current consensus statement based on
available evidence.

Study Highlights
Weight gain is common with both rosiglitazone and pioglitazone and may be due to both increased
caloric retention as well as fluid retention. When combined with a sulfonylurea, weight gain may
vary between 1.8 to 2.9 kg. Weight gain is even more significant when TZDs are combined with insulin
(average gain, 2.3 - 5.4 kg).
Edema is also frequently found in patients taking TZDs, occurring in 3% to 5% of patients using TZDs
as monotherapy. Rates of edema are higher if TZDs are used in combination with other hypoglycemic
agents. 13.1% to 16.2% of patients taking TZDs with insulin may experience edema.
CHF is not frequently encountered with TZD use. Rosiglitazone, either alone or in combination with
other oral hypoglycemic agents, is associated with an incidence of CHF of less than 1%. However, CHF
incidence rises to 2% to 3% if rosiglitazone is combined with insulin. Pioglitazone has been
associated with an incidence of CHF of 1.1%.
In reviewing case reports of CHF associated with the use of TZDs, the authors of the consensus
statement caution that TZDs may unmask previously asymptomatic cardiac insufficiency by increasing
plasma volume.
The recommendations of the consensus panel are as follows:
Before prescribing a TZD, the physician should perform a thorough history and physical for risk
factors, such as previous myocardial infarction or significant valvular disease, that could
predispose a patient to CHF. Baseline dyspnea and edema should be recorded.
Physicians should also pay attention to other medications, such as vasodilators, which may also
contribute to fluid retention.
Peripheral edema is not a contraindication for TZD use, but it should be monitored during TZD
therapy.
Patients should be instructed to report any weight gain more than 3 kg, new pedal edema, dyspnea, or
fatigue after starting a TZD.
In patients without known heart disease but with 1 or more cardiac risk factors, TZDs should be
started at the lowest possible dose and advanced cautiously with special attention to possible fluid
overload.
TZDs should be avoided if possible when the patient has a known reduced ejection fraction (<40%) but
is asymptomatic. Again, if TZDs must be used, the patient should be started on the lowest possible
dose and advanced cautiously.
TZDs also may be used with close patient supervision if the patient has known class I or II New York
Heart Heart Association (NYHA) CHF.
TZDs should be avoided in cases of class III or IV NYHA CHF.
If evidence of fluid overload manifests itself during TZD therapy, especially in the first few
months of treatment, the physician should mount a thorough investigation for CHF. This should
include an electrocardiogram, echocardiogram, and, possibly, serum evaluation for brain natriuretic
peptide.
If CHF is not present in a patient receiving TZDs with evidence of fluid overload, other drugs that
may contribute to increased intravascular volume should be reconsidered. The TZD also may be
discontinued or modified to a lower dose. Angiotensin-converting enzyme inhibitors with or without a
thiazide diuretic may help to reduce edema.
Any treatment-emergent CHF should prompt a reconsideration of the use of a TZD. If the TZD is
discontinued, symptoms of volume overload should be expected to resolve fairly quickly, and diuretic
therapy may be needed for only a short time.
Pearls for Practice
TZDs offer diabetic patients benefits beyond lowering serum glucose.
TZDs frequently lead to fluid retention. All patients receiving TZDs should be monitored for
symptoms and signs of fluid retention. TZDs should be avoided in patients with moderate to severe
CHF or evidence of an ejection fraction less than 40%.

Ok, I'm on 4mg daily of avandia and 5mg daily of elanapril for high blood
pressure. Does this mean that I should discontinue the avandia because I'm
in grave danger of having a heart attack due to the avandia?

Ok, I'm on 4mg daily of avandia and 5mg daily of elanapril for high blood
pressure. Does this mean that I should discontinue the avandia because I'm
in grave danger of having a heart attack due to the avandia?

Electromatic said this...

Avandia is containdicated for people with a history of heart disease.

Hypertension (high BP) is NOT a heart issue. It's a vascular issue.
Basically constriction of the blood vessels, which means the heart has
to work harder to push blood round. Hence increased pressure!

So Avandia isn't necessarily dangerous to someone with high BP on
medication.

Any other thoughts anyone?

ratty
--
www.flyingrat.net

Electromatic said this...

Avandia is containdicated for people with a history of heart disease.

Hypertension (high BP) is NOT a heart issue. It's a vascular issue.
Basically constriction of the blood vessels, which means the heart has
to work harder to push blood round. Hence increased pressure!

So Avandia isn't necessarily dangerous to someone with high BP on
medication.

Any other thoughts anyone?

ratty
--
www.flyingrat.net

"Electromatic" <groupbm@extramayo.com> wrote in message
news:x%PDb.529$zv4.416@newssvr27.news.prodigy.com. ..

"Electromatic" <groupbm@extramayo.com> wrote in message
news:x%PDb.529$zv4.416@newssvr27.news.prodigy.com. ..

I'm also taking 4mg of Avandia per day but my MD (cardiologist/general) has
me split it and take 1/2 in the morning and 1/2 in the evening. Wonder if
that has anything to do with a risk? I also take 80mg Zocor, 50mg Vioxx
,100mg Pletal and an 81mg aspirin. Haven't had any heart problems that I
know of and my blood pressure is great (knock on wood) but will run this by
my MD on next visit in February. Rob Mills

"Electromatic" <groupbm@extramayo.com> wrote in message
news:x%PDb.529$zv4.416@newssvr27.news.prodigy.com. ..

I'm also taking 4mg of Avandia per day but my MD (cardiologist/general) has
me split it and take 1/2 in the morning and 1/2 in the evening. Wonder if
that has anything to do with a risk? I also take 80mg Zocor, 50mg Vioxx
,100mg Pletal and an 81mg aspirin. Haven't had any heart problems that I
know of and my blood pressure is great (knock on wood) but will run this by
my MD on next visit in February. Rob Mills

"Electromatic" <groupbm@extramayo.com> wrote in message
news:x%PDb.529$zv4.416@newssvr27.news.prodigy.com. ..

Electromatic wrote:
I note the original warning says contra-indicated IF you a HISTORY or OTHER
RISK. So it seems to me like a high-protein diet damageing kidneys - panic
(quite understandable) leading to assuming that starting something off is
the same as making worse something already started.

jmo, but avandia/actos are perfectly safe if used correctly. Like everything
else they unsafe if used incorrectly.
--
Al.
Idiopathic t1
HbA1c 5.95
Total Chol 2.7
Blood Pressure 105/70
Beef Lente 1x
Beef Neutral 2x

Electromatic wrote:
I note the original warning says contra-indicated IF you a HISTORY or OTHER
RISK. So it seems to me like a high-protein diet damageing kidneys - panic
(quite understandable) leading to assuming that starting something off is
the same as making worse something already started.

jmo, but avandia/actos are perfectly safe if used correctly. Like everything
else they unsafe if used incorrectly.
--
Al.
Idiopathic t1
HbA1c 5.95
Total Chol 2.7
Blood Pressure 105/70
Beef Lente 1x
Beef Neutral 2x

Flying Rat wrote in message ...
The docs lump the various forms of heart disease into "heart disease"
in the press releases, then separate them in the discussion.

If you have diabetes then you are prone to ischemic heart disease, i.e. the
diabetes causes damage which encourages the plugging of arteries. The
TZD's like Actos and Avandia "fight" ischemic heart disease in diabetics and
therefore:

For many diabetics, Actos and Avandia are life-saving drugs.

However, the TZD's encourage fluid retention. If you are prone to
Congestive Heart Failure, (a "heart disease" different than Ischemic Heart
Disease) then:

For "you", the TZD's have a dangerous side effect.

The docs fling the buzz words around and don't make it easy for us amateurs
to pick out the differences. Note how they use "heart failure" all through
this quoted report but don't mention infarction which is the death-dealing
result of ischemic heart disease.

There is a bit of gallows humor in this whole subject.

a. In my family, folks die young from infarctions caused by ischemic
heart disease. However, we don't have problems with Congestive Heart
Failure. Therefore, we notice the life-saving effects of the anti-ischemic
meds and recommend them to everybody (e.g. I am always pushing the TZD's
in the newsgroups)

b. In some families, Congestive Heart Failure is a problem. Folks
with this genetic heritage notice the edema effects of the TZD's and are
quick to point out how dangerous they are.

Annette has relatives who suffer form congestive heart failure but don't
seem to suffer from ischemic heart disease. For her, Actos and Avandia are
dangerous drugs with unnecessary anti-ischemic heart disease benefits.

My wife has a pre-school grandchild. The "other" grandmother is a T2
diabetic.

The "other" grandmother has congestive heart failure and therefore is barred
from the life-saving benefits of Actos and Avandia.

My wife will enjoy her grandchild's exeriences as he progresses through
school. I don't think the "other" grandmother will live long enough to
watch her grandchild graduate from high school, perhaps not from middle
school, perhaps even not from kindergarden. That part is not humorous,
only sad.

Now, we must think about high blood pressure.

AFAIK, damage from high blood pressure can cause congestive heart failure.
Insulin Resistance produces high levels of circulating insulin which damages
arteries which causes high blood pressure.

Actos and Avandia are anti-Insulin Resistance meds. Therefore, they
fight high blood pressure, and thus also fight congestive heart failure.

Therefore:

Actos and Avandia have anti-heart disease effects in that:

a. They fight the high blood pressure which causes congestive
heart failure

b. They improve the lipid profiles/bG excursions which lead to
ischemic heart disease.

However, it you don't "catch" the congestive heart disease
problem/tendency/genetic predisposition?? soon enough, then you are
prohibited from enjoying the life-saving effects of Actos and Avandia.

Thus the doctors' dilemma.

a. If they avoid prescribing TZD's, they may exacerbate heart disease
tendencies, .

b. If they prescribe TZD's, they may exacerbate undiscovered heart
disease

One answer is to fight Insulin Resistance tooth and nail before getting into
that dilemma. The "other" grandmother lost that race.

That's why cardiologists refer to T2 as a cardiovascular disease marked by
occasional high blood sugars.

Regards
Old Al
(Say. . .there's this med called metformin which the Brits have been using
for 40 years and. . . .)

Flying Rat wrote in message ...
The docs lump the various forms of heart disease into "heart disease"
in the press releases, then separate them in the discussion.

If you have diabetes then you are prone to ischemic heart disease, i.e. the
diabetes causes damage which encourages the plugging of arteries. The
TZD's like Actos and Avandia "fight" ischemic heart disease in diabetics and
therefore:

For many diabetics, Actos and Avandia are life-saving drugs.

However, the TZD's encourage fluid retention. If you are prone to
Congestive Heart Failure, (a "heart disease" different than Ischemic Heart
Disease) then:

For "you", the TZD's have a dangerous side effect.

The docs fling the buzz words around and don't make it easy for us amateurs
to pick out the differences. Note how they use "heart failure" all through
this quoted report but don't mention infarction which is the death-dealing
result of ischemic heart disease.

There is a bit of gallows humor in this whole subject.

a. In my family, folks die young from infarctions caused by ischemic
heart disease. However, we don't have problems with Congestive Heart
Failure. Therefore, we notice the life-saving effects of the anti-ischemic
meds and recommend them to everybody (e.g. I am always pushing the TZD's
in the newsgroups)

b. In some families, Congestive Heart Failure is a problem. Folks
with this genetic heritage notice the edema effects of the TZD's and are
quick to point out how dangerous they are.

Annette has relatives who suffer form congestive heart failure but don't
seem to suffer from ischemic heart disease. For her, Actos and Avandia are
dangerous drugs with unnecessary anti-ischemic heart disease benefits.

My wife has a pre-school grandchild. The "other" grandmother is a T2
diabetic.

The "other" grandmother has congestive heart failure and therefore is barred
from the life-saving benefits of Actos and Avandia.

My wife will enjoy her grandchild's exeriences as he progresses through
school. I don't think the "other" grandmother will live long enough to
watch her grandchild graduate from high school, perhaps not from middle
school, perhaps even not from kindergarden. That part is not humorous,
only sad.

Now, we must think about high blood pressure.

AFAIK, damage from high blood pressure can cause congestive heart failure.
Insulin Resistance produces high levels of circulating insulin which damages
arteries which causes high blood pressure.

Actos and Avandia are anti-Insulin Resistance meds. Therefore, they
fight high blood pressure, and thus also fight congestive heart failure.

Therefore:

Actos and Avandia have anti-heart disease effects in that:

a. They fight the high blood pressure which causes congestive
heart failure

b. They improve the lipid profiles/bG excursions which lead to
ischemic heart disease.

However, it you don't "catch" the congestive heart disease
problem/tendency/genetic predisposition?? soon enough, then you are
prohibited from enjoying the life-saving effects of Actos and Avandia.

Thus the doctors' dilemma.

a. If they avoid prescribing TZD's, they may exacerbate heart disease
tendencies, .

b. If they prescribe TZD's, they may exacerbate undiscovered heart
disease

One answer is to fight Insulin Resistance tooth and nail before getting into
that dilemma. The "other" grandmother lost that race.

That's why cardiologists refer to T2 as a cardiovascular disease marked by
occasional high blood sugars.

Regards
Old Al
(Say. . .there's this med called metformin which the Brits have been using
for 40 years and. . . .)

Al,

These drugs are pretty new to the market, and it is only in the last couple
months that evidence of their damaging side effects has come to light. The
after-marketing procedure is tilted in the direction of letting the drug
manufacturers continue to market their drugs. Doctors must report the drug
side effect to the FDA (a cumbersome process) for it to get attention. But
doctors who give a patient Actos or Avandia and then saw them develop
congestive heart failure may not have connected the two--after all these
patients tend to be older and in poor health. And many doctors do not
report. I know that mine did not when I developed permanent tinnitus from
Clinoril.

So many people must die before the FDA takes another look. Look at how in
the US, antidepressants are still being prescribed to teenagers, though in
Britain it has become evident that they cause a much higher than expected
incidence of suicide and agitation. (I just saw a neighbor's friend have
exactly this reaction to one of the drugs banned for teens in the UK, alas.
Then they put her on the anti-psychotic that causes diabetes. She gained 40
lbs in 3 months, and I suspect that at 15 because of the initial
mis-presciption, they've just ruined her life. <sigh>)

So this is a situation where you have to be a bit paranoid about the
possibility of side effects because the chances are that the true incidence
of these new side effects is not known.

Nor can you trust that your doctor is up-to-date with the latest information
about side effects. I have learned this the hard way! I have been
misprescribed several drugs that are contraindicated for people with my drug
reaction history though I have spelled it out very clearly each time I go to
the doctor. Only be reading the prescribing info myself have I found how
inappropriate these prescriptions were.

The problem with Actos/Avandia as I see it is that there's some latitude in
discovering who is, in fact, "at risk" for heart failure (a terrible,
irreversible and eventually fatal condition.) If your doctor has run all
the tests mentioned in the article, perhaps you are safe. But if your doctor
(and HMO) is like mine, they haven't run those tests and won't until you
develop symptoms. So it isn't known if you are truly at risk for heart
failure

Plus, there is going to be a small number of people who develop the side
effect with no obvious warning. Maybe it's only 1 in 200,000 but if you're
that one, it means you die a lot earlier than necessary.

From what I've read on Medscape, my suggestion would be that anyone who
experiences sudden or swift weight gain of any type on these drugs should
stop taking them rather than gamble with their heart's ability to pump.

Also, these same drugs are also now associated with an increase macular
edema (swelling in the retina) and that can lead to blindness!

What's really sad, is that the people I know who are on Actos/Avandia
(including some relatives) were never told to try carbohydrate restriction
before committing to these potentially damaging drugs. At the big family get
together they sit shoveling down low fat potato salad and pasta which they
are convinced is healthy because their doctors told them to eat a low fat
diet. This past year I've watched one cousin (in her early 30s) gain 40 lbs
on Avandia. <sigh>
-- Jenny

Cut the carbs to respond to my new email address!
New photo: http://www.geocities.com/jenny_the_bean/jennypics.htm
Weight: 168.5/137
Diabetes Type II diagnosed 8/1998 -
HBa1c 5.2 10/03
Low Carb 9/1998 - 8/2001 and 11/10/02 - Now

http://www.geocities.com/jenny_the_bean
How to calculate your need for protein * How much people really lose each
month * Water Weight Gain & Loss * The "Two Gram Cure" for Hunger Cravings
* Characteristics of Successful Dieters * Indispensible Low Carb Treats *
Should You Count that Low Impact Carb? * Curing Ketobreath * Exercise
Starting from Zero * Do Starch Blockers Work? * NEW! Why the Low Carb Diet
is Great for Diabetes * NEW! Low Carb Strategies for People with Diabetes


"Al Hardy" <a.hardy2@ntlworld.com> wrote in message
news:brp97v$5seld$1@ID-191168.news.uni-berlin.de...

Al,

These drugs are pretty new to the market, and it is only in the last couple
months that evidence of their damaging side effects has come to light. The
after-marketing procedure is tilted in the direction of letting the drug
manufacturers continue to market their drugs. Doctors must report the drug
side effect to the FDA (a cumbersome process) for it to get attention. But
doctors who give a patient Actos or Avandia and then saw them develop
congestive heart failure may not have connected the two--after all these
patients tend to be older and in poor health. And many doctors do not
report. I know that mine did not when I developed permanent tinnitus from
Clinoril.

So many people must die before the FDA takes another look. Look at how in
the US, antidepressants are still being prescribed to teenagers, though in
Britain it has become evident that they cause a much higher than expected
incidence of suicide and agitation. (I just saw a neighbor's friend have
exactly this reaction to one of the drugs banned for teens in the UK, alas.
Then they put her on the anti-psychotic that causes diabetes. She gained 40
lbs in 3 months, and I suspect that at 15 because of the initial
mis-presciption, they've just ruined her life. <sigh>)

So this is a situation where you have to be a bit paranoid about the
possibility of side effects because the chances are that the true incidence
of these new side effects is not known.

Nor can you trust that your doctor is up-to-date with the latest information
about side effects. I have learned this the hard way! I have been
misprescribed several drugs that are contraindicated for people with my drug
reaction history though I have spelled it out very clearly each time I go to
the doctor. Only be reading the prescribing info myself have I found how
inappropriate these prescriptions were.

The problem with Actos/Avandia as I see it is that there's some latitude in
discovering who is, in fact, "at risk" for heart failure (a terrible,
irreversible and eventually fatal condition.) If your doctor has run all
the tests mentioned in the article, perhaps you are safe. But if your doctor
(and HMO) is like mine, they haven't run those tests and won't until you
develop symptoms. So it isn't known if you are truly at risk for heart
failure

Plus, there is going to be a small number of people who develop the side
effect with no obvious warning. Maybe it's only 1 in 200,000 but if you're
that one, it means you die a lot earlier than necessary.

From what I've read on Medscape, my suggestion would be that anyone who
experiences sudden or swift weight gain of any type on these drugs should
stop taking them rather than gamble with their heart's ability to pump.

Also, these same drugs are also now associated with an increase macular
edema (swelling in the retina) and that can lead to blindness!

What's really sad, is that the people I know who are on Actos/Avandia
(including some relatives) were never told to try carbohydrate restriction
before committing to these potentially damaging drugs. At the big family get
together they sit shoveling down low fat potato salad and pasta which they
are convinced is healthy because their doctors told them to eat a low fat
diet. This past year I've watched one cousin (in her early 30s) gain 40 lbs
on Avandia. <sigh>
-- Jenny

Cut the carbs to respond to my new email address!
New photo: http://www.geocities.com/jenny_the_bean/jennypics.htm
Weight: 168.5/137
Diabetes Type II diagnosed 8/1998 -
HBa1c 5.2 10/03
Low Carb 9/1998 - 8/2001 and 11/10/02 - Now

http://www.geocities.com/jenny_the_bean
How to calculate your need for protein * How much people really lose each
month * Water Weight Gain & Loss * The "Two Gram Cure" for Hunger Cravings
* Characteristics of Successful Dieters * Indispensible Low Carb Treats *
Should You Count that Low Impact Carb? * Curing Ketobreath * Exercise
Starting from Zero * Do Starch Blockers Work? * NEW! Why the Low Carb Diet
is Great for Diabetes * NEW! Low Carb Strategies for People with Diabetes


"Al Hardy" <a.hardy2@ntlworld.com> wrote in message
news:brp97v$5seld$1@ID-191168.news.uni-berlin.de...

Jenny wrote:
it seems that you are. Please to forgive if I got that wrong.

marketing is allowed? Sometimes here in the UK we are as much as a year
behind America in allowing new drugs. Sometimes an advantage, sometimes a
disadvantage. Here, we don`t have just one ageny involved, but at least two,
MAHRA and NICE, sometimes MAFF gets involved as well.

any new drug for any health problem.

and NICE are irrelevant in the US.

salbutamol, beclomethazone, insulin: without them I`m dead very quickly.

through 5 GPs in the past 7 years, but now I am satisfied.

May I ask (not sarcastically, I do actually want to know) what is
*carbohydrate restriction*, how low is *low-carb*? I am 5` 10" tall, weigh
139 lbs, physically active (on my feet at least 8 hours a day), no statins
or Met or Actos or anything has ever been prescribed or even hinted at, and
I am t1. And why would low-carb prevent the need for Actos/Avandia?

Nearly forgot, I do have a *slight* heart issue, enlarged left ventricle,
maternally inherited, predates diabetes by over 4 decades.
--
Al.
Idiopathic t1
HbA1c 5.95
Total Chol 2.7
Blood Pressure 105/70
Beef Lente 1x
Beef Neutral 2x

Jenny wrote:
it seems that you are. Please to forgive if I got that wrong.

marketing is allowed? Sometimes here in the UK we are as much as a year
behind America in allowing new drugs. Sometimes an advantage, sometimes a
disadvantage. Here, we don`t have just one ageny involved, but at least two,
MAHRA and NICE, sometimes MAFF gets involved as well.

any new drug for any health problem.

and NICE are irrelevant in the US.

salbutamol, beclomethazone, insulin: without them I`m dead very quickly.

through 5 GPs in the past 7 years, but now I am satisfied.

May I ask (not sarcastically, I do actually want to know) what is
*carbohydrate restriction*, how low is *low-carb*? I am 5` 10" tall, weigh
139 lbs, physically active (on my feet at least 8 hours a day), no statins
or Met or Actos or anything has ever been prescribed or even hinted at, and
I am t1. And why would low-carb prevent the need for Actos/Avandia?

Nearly forgot, I do have a *slight* heart issue, enlarged left ventricle,
maternally inherited, predates diabetes by over 4 decades.
--
Al.
Idiopathic t1
HbA1c 5.95
Total Chol 2.7
Blood Pressure 105/70
Beef Lente 1x
Beef Neutral 2x

oldal4865 wrote:
My thanks for this clear logical treatise.

oldal4865 wrote:
My thanks for this clear logical treatise.