S P E C I A L E D I T I O N 2012
Updates for physicians on practices, advances and research from Cleveland Clinic’s Endocrinology & Metabolism Institute
Endocrine Notes
{Surgical Treatment and Medications Potentially Eradicate Diabetes Efficiently}
Endocrine Notes | 1 | 2011
Dear Colleagues,Surgery Works for Diabetes.
The STAMPEDE story began more than 10 years ago. In 2003, Philip R.
Schauer, MD, published an intriguing study1 documenting the effects of gastric
bypass surgery on biochemical control of diabetes. Dr. Schauer looked at diabetic
patients who’d had the Roux-en-Y gastric bypass surgery and noted a significant
improvement in diabetes mellitus as measured by patients’ reduced need for
medications designed to bring blood sugar under control.
While this finding was hopeful, the response from endocrinology and cardio-
vascular specialists was muted. What was needed was a demonstration that
bariatric surgery could unequivocally produce biochemical resolution of the
disease. In 2007, Dr. Schauer, now Director of Cleveland Clinic’s Bariatric &
Metabolic Institute within the Endocrinology & Metabolism Institute, along with
colleagues Steven Nissen, MD, Chair of Cardiovascular Medicine, and endocri-
nologist Sangeeta Kashyap, MD, launched STAMPEDE (Surgical Treatment and
Medications Potentially Eradicate Diabetes Efficiently) to prove the safety and
efficacy of surgical treatment for diabetes. The results were published in the
New England Journal of Medicine.2
STAMPEDE enrolled patients with uncontrolled type 2 diabetes and randomly as-
signed them to medical therapy, Roux-en-Y gastric bypass or sleeve gastrectomy.
The endpoint was a level of glycated hemoglobin lower than 6 percent at one
year. The result? All three groups improved. But the surgical group enjoyed signifi-
cantly greater improvement than the others, with lower-to-no need for insulin or
cardiovascular medications.
STAMPEDE is a landmark clinical trial, extremely well-controlled with outstand-
ing medical treatment in both the surgical and pharmaceutical arms provided by
our expert endocrinologists under the direction of Dr. Kashyap. The findings are
meaningful and applicable to the population at large.
The STAMPEDE team is currently seeking funding to attempt to replicate these
results in a larger, multicenter trial. If it is able to do so, endocrinologists will have
a powerful new tool in their diabetes mellitus treatment armamentarium.
Sincerely,
James B. Young, MD Chairman, Endocrinology & Metabolism Institute
Professor of Medicine and Executive Dean, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University
George and Linda Kaufman Chair
Physician Director, Institutional Relations and Development
Endocrine NotesChairman, Endocrinology &
Metabolism Institute
James B. Young, MD
Managing Editor
Kimberley Sirk
Art Director
Mike Viars
Marketing
Bill Sattin, PhD
Mary Anne Connor
Endocrine Notes updates physicians on
clinical practices, advances and research
from Cleveland Clinic’s Endocrinology
& Metabolism Institute. It is written for
physicians and should be relied upon for
medical education purposes only. It does
not provide a complete overview of the
topics covered and should not replace the
independent judgment of a physician about
the appropriateness or risks of a procedure
for a given patient.
© 2012 The Cleveland Clinic Foundation
1. Ann Surg. 2003 October; 238(4): 467–485. 2. N. Engl. J. Med. 2012 April 26 [V. 366, No. 17]
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A Diabetes Treatment That is Worthy of Note By P h I L I P S C h A u E r , m D
In March 2012, we were pleased
to present the findings of a ran-
domized controlled trial comparing
bariatric surgery and medical treat-
ment for the management of type 2
diabetes at the annual meeting of the
American College of Cardiology and
published in the New England Journal
of Medicine. The single-center study
randomized 150 obese patients (BMI
27-43 kg/m2) with poorly controlled
diabetes (mean A1c > 9 percent)
to receive either sleeve gastrectomy,
Roux-en-Y gastric bypass or intensive
medical therapy - secondary endpoints
related to cardiovascular risk. All three
groups showed improvement in blood
sugar level at the end of one year. Of
the patients who were medically man-
aged, 12 percent achieved the primary
endpoint of hemoglobin A1c of 6
percent, compared to 37 percent of
those receiving sleeve gastrectomy and
42 percent having gastric bypass. (The
average BMI for patients at the begin-
ning of the study was 36. The patients
randomized to surgery lost about 60
pounds, with a post-treatment BMI of
about 26.) Patients in
the surgery group also
had greater reduction
in cardiovascular risk
factors and reduced
their dependency on
diabetes and cardio-
vascular medications.
These findings are
worthy of note by all
who are concerned
by the prospect of
managing what all
signs indicate will be an
increasing number of
new diabetes cases in
coming years. Indeed,
an editorial that ac-
companied the study’s
publication in the New England Journal
of Medicine described the diabetes
curve as “one of the fastest growing
epidemics in human history.”
Until now, diabetes has been seen
as a medical problem amenable only
to medical treatments. This study
demonstrates that surgery is superior to
medical treatment in achieving glycemic
control for patients with uncontrolled
diabetes. Proposing a surgical solution
inevitably brings up the question of risk.
In our study, the most common com-
plications were dehydration, managed
with intravenous fluids. A single patient
developed a surgical-site gastrointestinal
leak which resolved with surgical treat-
ment. Four of the 100 surgical patients
required additional surgeries to address
these complications during the post-
surgical year. There were no deaths,
long-term disability or life-threatening
complications.
Our high-volume bariatric surgery
practice at Cleveland Clinic has better
outcomes than the national average.
Nationally, 15 to 20 percent of patients
undergoing these procedures have mild
complications, 1 percent has serious
complications and 2 in 1,000 dies
(similar to the mortality figures for gall-
bladder surgery). There is no question
that patients seeking bariatric surgery
should seek out surgeons and centers
like Cleveland Clinic that have a great
deal of experience.
We also hear commentary on the
implied economics of the study. The
surgeries we studied involved costs of
around $25,000. Theoretically, most
patients with diabetes mellitus can
control their blood sugar with diet,
exercise and medication. However,
many patients with uncontrolled diabe-
tes on medical therapy will experience
complications including heart and
kidney disease, or loss of limbs and
vision – and millions of dollars may
be expended to treat conditions that
we now believe could be prevented
by timely surgical intervention.
The STAMPEDE study is one of
the first randomized controlled trials
demonstrating the superiority of sur-
gery compared with intensive medical
treatment for patients with obesity
and type 2 diabetes. Given the good
safety profile of bariatric surgery, clini-
cians should consider recommending
surgery for patients with uncontrolled
diabetes and obesity. ■
Our high-volume
bariatric surgery practice
at Cleveland Clinic has
better outcomes than
the national average.
Endocrine Notes | 2 | Special Edition 2012
An Endocrinologist’s View: Two-Year Follow-Up By S A N g E E TA k A S h y A P, m D
T he STAMPEDE trial showed
that two methods of bariatric
surgery resulted in marked
weight loss and biochemical remission
of diabetes as measured by blood glu-
cose levels. However, among patients
who received either the Roux-en-Y
gastric bypass or sleeve gastrectomy,
those having the bypass achieved
significantly higher rates of remis-
sion – 33 percent as opposed to 10
percent at the two-year follow-up. Yet
both groups had a similar reduction in
body weight and BMI, suggesting that
weight loss was not the only mecha-
nism for remission.
A metabolic substudy of the two-year
extension of STAMPEDE gave us the
answer. We learned that the gastric
bypass resulted in a significantly larger
loss of abdominal fat compared with
the sleeve gastrectomy – about 5
percent more.
We looked at meal glucose responses
in the first 60 patients who had been
randomized to one or the other of the
surgical groups. They were mostly in
their late 40s with a mean BMI of 36
and diabetes of seven to 10 years’ du-
ration. Many had metabolic syndrome.
All were on medication, some on three
or more, and half required insulin. Both
groups were at a baseline of 150 mg/
dL at the beginning and 250 mg/dL at
the end of meal intake. But the two-
year results were startling: The patients
who’d had gastric bypass had normal
glucose levels of 85-100 mg/dL before
and after meal intake. The sleeve
gastrectomy group had intermediate
glucose levels despite having lost the
same amount of weight.
At both 1 and 2 years follow-up, the
gastric bypass patients had achieved
nearly normal glucose tolerance follow-
ing a physiological liquid mixed meal.
These effects were associated with
a remarkable 5.8 fold increase in over-
all pancreatic beta cell function.
Both bariatric surgery procedures stimu-
lated insulin production and incretins
with markedly increased postprandial
GLP-1 levels, as noted in previous
observational studies of obese patients
with type 2 diabetes.
Greater effects on insulin sensitivity were
noted with gastric bypass compared with
sleeve gastrectomy, despite similar weight
loss.Both procedures produced similar
weight loss, reduction in body fat and
leptin levels. However, greater reduction
in abdominal fat was noted with gastric
bypass than sleeve gastrectomy.
So we conclude that in moderately
obese patients with uncontrolled type 2
diabetes, bariatric surgery provides more
durable glycemic control compared with
intensive medical therapy at two years.
Despite similar weight loss as sleeve
gastrectomy, gastric bypass uniquely re-
stores pancreatic beta cell function and
reduces abdominal fat, targeting the key
cardiometabolic defects in diabetes.
Medical therapy has always targeted
pancreatic hormonal failure to slow down
the advancement of the disease. Our
findings suggest that bariatric surgery
could potentially reverse the disease and
maybe stop it in its tracks. It deserves
the attention of endocrinologists and the
entire medical community. ■
A substudy of
two-year results of
STAMPEDE gave us
the answer. We learned
that the gastric bypass
resulted in a significantly
larger loss of abdominal
fat compared with the
sleeve gastrectomy –
about 5 percent more.
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Good News from an Unexpected Quarter By S T E v E N N I S S E N , m D
T he obesity epidemic is emerg-
ing as the greatest threat to 50
years of progress in reducing
the burden of cardiovascular disease
in developed countries. The incidence
of type 2 diabetes has skyrocketed
in recent years. Some projections
suggest that by the year 2050, half
of the U.S. population will develop
diabetes during their lifetime.
In our coronary care unit, about half
of all patients are diabetic. Weight
loss is highly effective at preventing
the development of diabetes and also
reduces obesity-related complications
such as hypertension. But changing
lifestyles and attitudes hasn’t been easy.
To overcome these limitations, we have
to look outside the usual paradigms.
The STAMPEDE trial provided an ag-
gressive and highly effective approach to
obesity and diabetes: bariatric surgery.
Clinicians observed that obese diabetics
who underwent bariatric surgery showed
lower blood sugar levels within hours
and days of the operation. Some authori-
ties have suggested that the procedure
altered gastrointestinal hormones,
thereby helping to control diabetes.
Some of these early observations
originated from bariatric surgeons and
endocrinologists at Cleveland Clinic,
particularly Drs. Philip Schauer and
Sangeeta Kashyap. These physician-
scientists sought to investigate this
phenomenon in depth. As Chair of
Cardiovascular Medicine, I was proud
to be asked to participate in the study
that became known as STAMPEDE.
The authors and their teams designed
a randomized clinical trial that would
provide strong and highly reliable data.
We had outstanding support from the
Cleveland Clinic Coordinating Center
for Clinical Research in the design and
execution of the trial,
and the added ad-
vantage of working in
a multispecialty group
practice culture that
promotes innovative
research.
STAMPEDE was
a comparison
of intensive medi-
cal therapy alone
versus medical
therapy plus bariatric
surgery. (Some have
characterized the
comparison as being
with bariatric surgery
alone. All patients re-
ceived very aggressive
medical treatment.)
The subjects were patients with uncon-
trolled type 2 diabetes. The paper was
published in the New England Journal
of Medicine in April 2012. As one of the
first controlled trials to test the effective-
ness of bariatric surgery in diabetics, the
results received tremendous public and
scientific attention.
The medically treated patients did
well. Twelve percent of the patients who
received medicine alone saw their blood
sugar drop to normal levels. But among
the patients who got both medicine and
surgery, the results were extraordinary.
Almost half of this group saw their blood
sugar return to normal. From a biochemi-
cal point of view, they were “cured.”
We are gratified by what we’ve learned
from STAMPEDE, but we are not blind
to the limitations of this study. It was a
small, single-center study with only a
year’s follow-up. The bariatric surgery
itself produced some modest adverse
effects that need to be examined
further. The study team is currently in
the midst of a four-year extension study
to look at long-term effects. We look
forward to the larger, multicenter trials
necessary to determine the effective-
ness of bariatric surgery plus medicine
on cardiovascular outcomes.
Today, only about 1 percent of
Americans who qualify for bariatric
surgery are offered this treatment.
Additional research confirming and
extending our findings could increase the
demand for bariatric surgery. Bariatric
surgery can cost $25,000. When you
compare the bill for a one-time bariatric
surgery to the expenses incurred over a
lifetime of diabetic care, often culminat-
ing in lengthy treatment for coronary
heart disease, the surgery may be a
good investment. STAMPEDE includes
a five-year follow-up to assess the
economic impact of the treatment.
My colleagues and I look forward to
continuing to work with endocrinolo-
gists, bariatric surgeons and primary
care physicians to pursue the most
promising treatments for diabetes
and slow its devastating growth. ■
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