Diabetic drugs...

Quote:

Hi,

There have been only three large long term clinical trials done to
study the cardiovascular and overall mortality effect of diabetic
drugs. The first was stopped early due to excess mortality in the drug
groups. PMID: 8901685 The second reported no benefit or detriment
on total mortalilty. PMID: 11503841 The first was largely ignored by
reviewers, but the second was reviewed so frequently and so badly that
a couple of doctors in Pennsylvania were motivated to expose the very
misleading response to it. PMID: 12896940 The third has now been
published, but is not yet in medline, I post a long popular article on
it below. It has also been stopped early due to excess mortality. It
appears that larger doses and combinations of drugs lowering glucose
levels to near normal, rather than standard treatment which leaves
them a bit higher causes excess mortality as well.

The authors of the new study say there is an unknown mechanism causing
the excess death. It seems clear to me that very likely mechanism is
the importing of glucose to cells when they have no need for it. While
hi levels of plasma glucose may be dangerous these papers clearly show
the hi probability that glucose is yet more harmful inside the body’s
cells. The scientific community can not accept this explanation since
it abrogates over three decades of medical practice, and acceptance
will severly impact sales of diabetic drugs.

While low doses of diabetes drugs seem to do no harm for about a
decade of use, patients who are prescribed them to “control their
diabetes” will rely less on the only proven interventions which are
diet and exercise. Acarbose may also be beneficial. I attach a review
paper on it as well. It slows absorption of glucose. So does fiber
consumption which also prevents diabetic events.

Thomas

Cardiovasc Drugs Ther. 2008 Feb 29 [Epub ahead of print] Links
Effect of Acarbose on Vascular Disease in Patients with Abnormal
Glucose Tolerance.
Hanefeld M, Schaper F, Koehler C.
Center for Clinical Studies, GWT-TUD GmbH, Fiedlerstraße 34, 01307,
Dresden, Germany, hanefeld at (no spam) gwtonline-zks.de.
INTRODUCTION: Excessive postprandial (pp) glucose
excursion in people with IGT and type 2 diabetes is associated with a
cascade of proatherogenic events. Acarbose, a potent competitive
inhibitor of alpha-glucosidases of the small intestine specifically
reduces pp hyperglycemia with an average reduction of HbA1c by 0.8% in
Cochrane metaanalysis. This is associated with pleiotropic effects on
a broad spectrum of cardiovascular (CV) risk factors: reduction of
overweight, lowering of blood pressure, triglycerides, hsCRP,
fibrinogen and other biomarkers of low grade inflammation. RESULTS AND
DISCUSSION: Flow mediated vasodilation was improved and progression of
intima media thickness was reduced by acarbose. In the STOP-NIDDM
trial in people with IGT acarbose decreased the incidence of diabetes
by 36%. The STOP-NIDDM trial with CV events as secondary objective is
the only intervention trial in people with IGT so far with a
significant benefit for CV disease inclusive hypertension. In a
metaanalysis of controlled studies (MeRIA) in patients with type 2
diabetes, treatment with acarbose was associated with a 64% lower rate
of myocardial infarction and 35% less CV events. CONCLUSION: Thus
results so far available prove that acarbose is an effective and safe
drug to treat abnormal glucose tolerance. They suggest that acarbose
can help to control a broad spectrum of CV risk factors and may
prevent CV disease.PMID: 18309462

Public release date: 6-Jun-2008
[ Print Article | E-mail Article | Close Window ]
Contact: NHLBI Communications Office
NHLBI_news at (no spam) nhlbi.nih.gov
301-496-4236
NIH/National Heart, Lung and Blood Institute
ACCORD clinical trial publishes results
A therapeutic strategy targeting blood sugar to near-normal levels
does not reduce cardiovascular events but increases mortality in
persons with diabetes at high risk
Intensively targeting blood sugar to near-normal levels in adults with
type 2 diabetes at especially high risk for heart attack and stroke
does not significantly reduce the risk of major cardiovascular events,
such as fatal or nonfatal heart attacks or stroke, but increases risk
of death, compared to standard treatment. Researchers from the ACCORD
(Action to Control Cardiovascular Risk in Diabetes) clinical trial
compared a medical strategy aimed at near-normal blood sugar levels â
€" below current recommendations -- to a strategy to reach more
standard blood sugar levels. Supported by the National Institutes of
Health, the study evaluated the effects of intensively targeting blood
sugar control among adults with established diabetes, high blood sugar
levels, and pre-existing heart disease or at least two cardiovascular
disease risk factors in addition to diabetes.
The first published results of the ACCORD trial of over 10,000
participants appear online in the New England Journal of Medicine
(NEJM) today and will be in the June 12 NEJM print edition. The
results are being presented at the American Diabetes Association's
68th Annual Scientific Sessions in San Francisco on June 10.
In February, the NIH's National Heart, Lung, and Blood Institute
(NHLBI) stopped the intensive blood sugar strategy after an average of
3.5 years of treatment, instead of the planned 5.6 years, due to
safety concerns. The intensive strategy group had a 22 percent higher
risk of death â€" or 54 more deaths -- compared to the standard group.
The increased risk began emerging within 1 to 2 years after the
strategy began to aggressively lower the participantsâ€™ blood sugar
levels. All participants now follow a medical strategy to reach the
standard blood sugar levels while other components of the study
continue.
"ACCORD is providing important evidence to help guide treatment
recommendations for adults with established type 2 diabetes who have
had a heart attack or stroke or who have two or more risk factors for
cardiovascular disease in addition to diabetes," said NHLBI Director
Elizabeth G. Nabel, M.D. "For these individuals, intensively lowering
blood sugar to near-normal levels appears to be too risky."
The researchers caution that the results might not apply to patients
who are at lower risk of cardiovascular disease than the ACCORD
participants or to patients with more recently diagnosed type 2
diabetes. On average, ACCORD participants had been diagnosed with
diabetes for 10 years at enrollment.
ACCORD's ongoing studies of the effects of aggressively
lowering blood pressure and treating multiple blood lipids
(cholesterol and triglycerides) in high-risk diabetic patients are
expected to continue through June 2009.
"Adults with type 2 diabetes are two to four times more likely than
adults without diabetes to die from heart disease, so identifying the
safest and most effective ways to help them lower their risk of heart
disease, stroke, and death is critical," Nabel noted. An estimated 21
million Americans have diabetes and 284,000 die from it each year.
Sixty-five percent of deaths in persons with diabetes are from
cardiovascular causes.
Conducted at 77 sites nationwide and in Canada,
ACCORD randomly assigned 10,251 participants between the ages 40 and
79 (average age 62) to standard or intensive blood sugar treatment
goals. Therapy in both groups included patient education and
counseling, and treatment with any of the major classes of Food and
Drug Administration-approved diabetes medications, as prescribed by
their study clinician: metformin, thiazolidinediones (TZDs, primarily
rosiglitazone), insulins, sulfonylureas, exanatide, and acarbose.
Combinations of medications could be used as needed to reach the
treatment goals.
Hemoglobin A1C levels, a standard measure of average blood sugar
levels over the preceding two to three months, were used to monitor
participants' blood sugar. The standard strategy group (5,123
participants) aimed to lower blood sugar levels to an A1C of 7 to 7.9
percent â€" a target similar to what is achieved, on average, by
individuals treated for type 2 diabetes in the United States. The
intensive strategy group (5,128 participants) had an A1C blood sugar
target of less than 6 percent â€" similar to that found in adults
without diabetes. To join the study, participants needed to have an
A1C level of 7.5 percent or higher; at study enrollment, one-half of
the participants had an A1C level over 8.1 percent.
Half of the participants in the standard strategy
group achieved an A1C less than 7.5 percent, and half of the intensive
strategy group achieved an A1C less than 6.4 percent. On average,
participants in both groups achieved these levels within the first
year of the study and maintained them throughout the study.
After an average of 3.5 years, 257 people in the intensive strategy
group died, compared to 203 participants in the standard strategy
group. This difference of 54 deaths resulted in a 22 percent increased
death rate in the intensive group. Causes of death were similar in
each group, with about half from cardiovascular conditions, such as
heart attack, sudden cardiac death, stroke, or heart failure. However,
the intensive group had 41 more cardiovascular deaths than the
standard group, resulting in a 35 percent higher cardiovascular death
rate.
"Despite detailed analyses, we have been unable to identify the
precise cause of the increased risk of death in the intensive blood
sugar strategy group," noted lead author Hertzel C. Gerstein, M.D.,
M.Sc. "Our analyses to date suggest that no specific medication or
combination of medications is responsible. We believe that some
unidentified combination of factors tied to the overall medical
strategy is likely at play." Gerstein holds the Population Health
Research Institute Chair in Diabetes and is director of the Division
of Endocrinology & Metabolism and Diabetes Care and Research Program
at McMaster University and Hamilton Health Sciences, Hamilton, Canada.
To meet their more aggressive targets, participants in the intensive
group used more medications, were more likely to use combinations of
medications, and changed medications and/or doses of medications more
frequently than those in the standard group. For example, 52 percent
of participants in the intensive strategy group were on three oral
medications plus insulin compared with 16 percent of participants in
the standard strategy group. The intensive strategy was associated
with more adverse side effects from medications, hypoglycemia (low
blood sugar) events, weight gain, and fluid retention.
The researchers also studied whether participants'
characteristics at enrollment had an impact on their outcomes. They
compared persons with and without existing cardiovascular disease,
women and men, those older and younger than age 65, those with A1C
levels lower and higher than 8 percent, and white and non-white
participants. Death rates were consistently higher in the intensive
strategy group regardless of baseline characteristics. However,
compared to participants in the standard group, those in the intensive
group who began the study with no history of heart attack or stroke,
or with lower blood sugar levels (A1C level 8 percent or less) had
fewer combined cardiovascular events â€" fatal and nonfatal heart
attacks or strokes â€" during the study.
The increased risk of death from the intensive
strategy surprised researchers and other experts because earlier
studies had shown that blood sugar at near-normal levels was
associated with lower cardiovascular disease risk in people with type
2 diabetes. However, these were observational studies, rather than
randomized clinical trials, as they did not test treatments to reduce
blood sugar. In addition, intensive blood sugar control has been shown
in clinical trials to reduce microvascular complications from diabetes
â€" including eye, kidney, and nervous system diseases â€" in people
with type 1 or type 2 diabetes, and to lower cardiovascular disease
risk in people with type 1 diabetes. However, the levels tested in
other studies were not at as low as the level targeted in the ACCORD
intensive treatment group.
The American Diabetes Association's clinical
guidelines recommend that most people with type 2 diabetes reach and
maintain an A1C of less than 7 percent. The guidelines also state that
treatment should be individualized. For example, a less stringent A1C
goal should be considered for people with severe or frequent low blood
sugar or with other medical conditions.
"The ACCORD results can now be considered when
doctors are tailoring blood sugar strategies for adults with type 2
diabetes who are at especially high risk for cardiovascular disease,"
said Denise G. Simons-Morton, M.D., Ph.D., a coauthor and NHLBI
project officer for ACCORD.
Future analyses from ACCORD will determine the
effects of the intensive blood sugar strategy on microvascular
diseases, cognition, quality of life, and other outcomes in the study
participants.