Bariatric Surgery

Report
Treating Type 2 Diabetes in
Obese Patients with Bariatric /
Metabolic Surgery
Highlights of Evidence from Recent Studies
NAME
DATE
©2012 Ethicon Endo-Surgery, Inc. DSL# 12-1088
Metabolic Surgery
Metabolic Surgery defined:
Alteration of the gastrointestinal tract that affects cellular and molecular signaling
leading to a physiologic improvement in energy balance, nutrient utilization and
metabolic disorders.
Kaplan LM, Seeley RJ, Harris JL. Bariatric Surgery and the Road Ahead, Bariatric Times, 9 (9): Supplement C, September
2012. http://bariatrictimes.epubxp.com/i/82655
2
Evidence Summary
• Recent RCT evidence supports cohort studies & metaanalyses showing bariatric / metabolic surgery can lead to
improvement or resolution of Type 2 Diabetes (T2DM) &
other CV co-morbidities – and reduce medication usage
• New data shows bariatric surgery may prevent T2DM
• Bariatric surgery has demonstrated safety similar to many
other general surgery procedures
• Major professional medical societies support bariatric surgery
– for treatment of T2DM in severely obese patients (BMI>40),
and also for obese patients with poorly controlled or
uncontrolled diabetes (BMI>35).
page 3
Implications for Payers
Short-term: Bariatric / metabolic surgery is able to achieve
improved glycemic control of Type 2 diabetes in selected
obese patients (BMI>35).
o Benefits for up to 2 years now shown in RCTs and up to
5 years in matched cohort studies with large groups of
patients
Long-term: Durability of this effect has yet to be fully
characterized & potential benefits have yet to be definitively
proven in routine clinical practice.
o Exception: Swedish Obesity Subjects study* – 15+ year
evidence suggests CV benefit, T2DM prevention &
prolonged glycemic control
* Sjostrom, L et al. Bariatric Surgery and Long-term Cardiovascular Events. JAMA 2012; 307(1):56-65
Carlsson, L et al, Bariatric Surgery and Prevention of Type 2 Diabetes in Swedish Obese Subjects.
NEJM 2012; 367:695-704.
4
Implications for Referring Physicians
Bariatric / metabolic surgery can achieve better control of Type 2
diabetes with much less medication in select obese patients (BMI>35)
o Focus on those patients who are at highest risk of a CV event:
• Younger (under 60)
• Treated less than 10 years
• Difficulty maintaining glycemic control with pharmacological agents.
• Having at least one other CV risk factor in addition to T2DM, e.g.
elevated insulin, hypertension and/or dyslipidemia.
• Difficulty maintaining acceptable weight (almost all T2DM patients).
o Surgery is a therapeutic intervention, not just for severely obese
patients.
o Mode of action of bariatric surgery is metabolically analogous to
many T2DM medications with positive impact on GLP-1 & insulin
sensitivity.
Sjostrom, L and others. Bariatric Surgery and Long-term Cardiovascular Events. JAMA 2012; 307(1):56-65.
Berry, J. and others. Lifetime Risks of Cardiovascular Disease. NEJM 2012; 366:321-29.
5
Body of Evidence
High Quality (Level I & II-1,2) Studies on Bariatric / Metabolic
Surgery in Diabetic Patients
Investigator
Study Type
# Diabetic Patients
Primary Endpoint
Study Duration
Carlsson
Non-randomized, prospective,
controlled
3429 pts, 2 arms
(1658 surgery)
Rate of incident type 2
diabetes mellitus
15 years
STAMPEDE
(Schauer)*
RCT, single center
150 pts, 3 arms
HbA1c < 6 with or w/o meds
Year 1 of
5-year study
Mingrone
RCT, single center
60 pts, 3 arms
HbA1c < 6.5 without meds
2 years
Buchwald*
Systematic Review &
Meta-Analysis
Klein*
Matched Cohort, Claims data
1600 pts, 2 arms
Economic impact & clinical
benefits of bariatric surgery
3 years
AHRQ (Segal)*
Matched Cohort, Claims data
8400 pts, 2 arms
(2100 surgery)
Impact of surgery to reduce
utilization of CV meds
Year 1 of
3-year study
Bolen*
Matched Cohort, Claims data
14,000 pts, 2 arms
(6300 surgery)
% Obesity-related comorbidities between groups
5 years
Cohen
Non-randomized, prospective
66 pts, 1 arm
Safety and % of patients
experiencing diabetes
remission
5 years
(median)
* Supported by a grant from Ethicon Endo-Surgery
7
135,000 pts, 621 studies, Effect of bariatric surgery on
888 arms
Type 2 diabetes
N/A
Discussion….
“What are your thoughts?”
Clinical Evidence:
STAMPEDE
Surgical treatment and medications achieved glycemic
control in more patients than medical therapy alone.
Schauer PR, Kashyap SR, Wolski K, et al. Bariatric Surgery versus
Intensive Medical Therapy in Obese Patients with Diabetes. N Engl
J Med. 2012; 366:1567-1576.
Study supported by a grant from Ethicon Endo-Surgery.
STAMPEDE
Study Design
* As defined by ADA guidelines, including lifestyle counseling, weight management, frequent home glucose monitoring, and the use of newer drug therapies.
page 10
STAMPEDE
Results: Significantly More Diabetic Patients at Glycemic Control
with Bariatric / Metabolic Surgery
“In obese patients with uncontrolled type 2 diabetes, 12 months of medical
therapy plus bariatric surgery achieved glycemic control in significantly
more patients than medical therapy alone.”
Patients at Glycemic Control, 12 months
45%
40%
42%*
35%
37%
**
30%
25%
20%
15%
10%
12%
5%
0%
Medical Therapy
Medical Therapy +
Gastric Bypass
Medical Therapy +
Sleeve Gastrectomy
*p=0.002
**p=0.008
Glycemic control: HbA1c < 6.0% with or without diabetes medications, 12 mo after randomization. Figures adapted from study data.
page 11
STAMPEDE
Results: Average levels of HbA1c were also significantly lower
after Bariatric / Metabolic Surgery
“Mean levels of glycated hemoglobin and fasting plasma glucose
were significantly lower in each of the two surgical groups than in the
medical therapy group”(p<0.001).
page 12
STAMPEDE
Results: Significant Decreases in Diabetic Medication Usage with
Bariatric / Metabolic Surgery
The average number of diabetic medications per patient per day tended to
increase in the medical therapy group but decreased significantly in each
surgical group (p<0.001):
> 50% of patients in each surgical group used
NO diabetes medications at 12 months.
page 13
Clinical Evidence:
Mingrone
Bariatric surgery resulted in better glucose control
than did medical therapy
Mingrone, G, et. al. Bariatric Surgery versus Conventional Medical
Therapy for Type 2 Diabetes, N Engl J Med 2012; 366:1577-1585.
Mingrone et al.
Study Design
page 15
Mingrone Study
Glycated Hemoglobin Levels during 2 Years of Follow-up
16
New Clinical Evidence:
Swedish Obese Subjects (SOS)
Bariatric surgery appears to be markedly more efficient
than usual care in the prevention of Type 2 diabetes in
obese persons.
Carlsson LMS, Peltonen M, Ahlin S et al, Bariatric Surgery and
Prevention of Type 2 Diabetes in Swedish Obese Subjects. N Engl J
Med 2012; 367:695-704.
Carlsson et al.
Study Design
18
Carlsson et al.
Results: Significantly lower incidence of Type 2 Diabetes in
Bariatric / Metabolic Surgery group
19
Sjostrom et al. (2012)
Bariatric Surgery Prevents CV Events
“High insulin may be a better selection criteria for bariatric surgery
than high BMI, as far as CV events are concerned”
Sjostrom, L et. al., Bariatric Surgery and Long-term Cardiovascular Events. JAMA 2012; 307(1):56-65; illustration from page 63.
20
Clinical Evidence
Bariatric / Metabolic Surgery and
Diabetes Management
Matched Cohort Studies / Administrative Claims Data
Buchwald: Systematic Review & Meta-Analysis (2009)
T2DM resolved or improved in 87% of patients following bariatric surgery
100%
99%
87%
81%
87%
85%
Gastroplasty
Gastric
Bypass
80%
60%
40%
20%
0%
Total
Total
Gastric
Banding
Resolved
BPD/DS
Resolved or Improved
• Systematic review & meta-analysis reviewing 621 studies including 135,246 patients
• Overall, T2DM 87% resolved or improved (78% resolved) for patients after bariatric surgery
Buchwald H, Estok R, Farbach K, et al. Weight and Type 2 Diabetes after Bariatric Surgery:
Systematic Review and Meta-analysis. Am J Med. 2009;122(3):248-256. Figure adapted from source
data. Data included includes 621 studies with 888 treatment arms & 135,246 patients; 103 treatment
arms with 3188 patients reported on resolution of diabetes.
22
Klein: 3-Year Matched Cohort Analysis (2011)
46% fewer T2DM-related claims for patients following bariatric surgery
• 3-year matched cohort analysis comparing claims from 1,616 privately insured patients (808 per
cohort)
• At 6 months, 28% of surgery patients reported a diabetes claim vs. 74% of control patients (p<0.001)
• The trend in diabetes claims was sustained to 3 years.
Source: Klein S, Ghosh A, Cremieux PY, Eapen S, McGavock TJ. Economic impact of the clinical
benefits of bariatric surgery in diabetes patients with BMI ≥35 kg/m2. Obesity. 2011;19:581-587.
23
Bolen: 5-Year Matched Cohort Analysis (2012)
Lower proportion – and likelihood - having T2DM at 5yr following bariatric surgery
• 5-year matched cohort analysis comparing 22,693 obese patients with versus without bariatric surgery
from seven BCBS plans
• The proportion of patients with T2DM at 5 years was 18% lower with bariatric surgery (15% vs. 33%)
• Bariatric surgery patients had a 31% lower likelihood (odds ratio) of having T2DM at 5 years
Source: Bolen, Shari and others. Clinical Outcomes after Bariatric Surgery: A Five-Year Matched
Cohort Analysis in Seven US States. Obesity Surgery (2012) 22: 749-763, Figure adapted from
source data. Non-concurrent, matched cohort study following 22,693 persons who underwent
bariatric surgery using logistic regression between groups for up to 5 years.
24
Clinical Evidence
Bariatric / Metabolic Surgery and
Diabetes Management (BMI 30-35)
Prospective Study
Cohen: 5-Year Study of Diabetic Patients (2012)
88% of diabetic patients without severe obesity showed diabetes remission
• Study of 66 consecutive diabetic patients with BMI 30-35 who underwent RYGB.
• At median 5 years, durable diabetes remission occurred in 88% of cases, and diabetes improvement in an
additional 11%.
• There was no recurrence of diabetes following remission during [the] six-year follow-up.
• Hypertension and dyslipidemia also improved, yielding 50-84% reductions in predicted 10-year
cardiovascular disease risks of fatal and nonfatal coronary heart disease and stroke.
Source: Cohen RV, Pinheiro JC, Schiavon CA et al. Effects of gastric bypass surgery in patients with
type 2 diabetes and only mild obesity. Diabetes Care 2012; 35:1420-1428.
26
Clinical Evidence
Bariatric / Metabolic Surgery and
Medication Usage
Matched Cohort Studies/Administrative Claims Data
Segal: AHRQ 1-Year Cohort Study (2010)
76% decline in diabetes medication use at 12 months post-surgery (p≤0.0001)
■ nonsurgical group
◊ surgical group
• 3-year cohort study using BCBS data from 7 plans, covering 6,235 patients (34% of whom had T2DM)
• 55% decrease in the mean number of diabetes medications within three months
• Patients without surgery had an increase in mean number of diabetes medications during the same period
Source: Segal JB, Clark JM, Shore AD, et al. Prompt reduction in use of medications for comorbid
conditions after bariatric surgery. Effective Healthcare Research Report No. 28. Rockville, MD: Agency
for Healthcare Research and Quality; 2010. (Fig 1, page 14)
28
Segal: AHRQ 1-Year Cohort Study (2010)
Significant declines in cardiovascular medication use at 12 months post-surgery
• Use of medication for hypertension & hyperlipidemia declined 51% and 59%, respectively, at 12
months post-surgery(p<0.0001)
• Patients without surgery had an increase in medications for hypertension and hyperlipidemia
Source: Segal JB, Clark JM, Shore AD, et al. Prompt reduction in use of medications for comorbid
conditions after bariatric surgery. Effective Healthcare Research Report No. 28. Rockville, MD: Agency
for Healthcare Research and Quality; 2010. (Fig 1, page 14)
29
Klein: 3-Year Matched Cohort Analysis (2011)
56% fewer diabetes prescriptions were filled for bariatric surgery patients
• 3-year matched cohort analysis covering 1,616 obese patients with diabetes (808 per cohort)
• Six months post-surgery, only 34% of surgery patients had filled a prescription for diabetes
medication in the previous three months, compared to 90% of control patients (p<0.001)
• This difference is sustained to the end of the study period (three years)
Source: Klein S, Ghosh A, Cremieux PY, Eapen S, McGavock TJ. Economic impact of the clinical
benefits of bariatric surgery in diabetes patients with BMI ≥35 kg/m2. Obesity. 2011;19:581-587.
Figure adapted from study data.
30
Klein: 3-Year Matched Cohort Analysis (2011)
Significantly lower supply costs in diabetes medication for surgery patients
P < 0.001
• Total diabetes medication costs decreased significantly among surgery patients relative to controls.
• 3 months after bariatric surgery, the average total cost of diabetes medications and supplies for
surgery patients was $33, compared to $123 for control patients (p<0.001)
• Total monthly prescription drug costs for surgery patients were 72% lower at two years.
Source: Klein S, Ghosh A, Cremieux PY, Eapen S, McGavock TJ. Economic impact of the clinical
benefits of bariatric surgery in diabetes patients with BMI ≥35 kg/m2. Obesity. 2011;19:581-587.
Figure adapted from study data.
31
Clinical Evidence
Bariatric Surgery Safety
Matched Cohort Studies/Administrative Claims Data
CMS: Inpatient Discharge Data (2010)
Morbidity & mortality rates of gastric bypass are similar to other common
procedures
Source: Direct Research, LLC, Center for Medicare and Medicaid Services, FY 2010 MedPAR,
Medicare Fee-for-Service Inpatient Discharges with Selected Procedures
33
UHC Database: Surgery Data (2012)
Morbidity & complication rates of laparoscopic bariatric surgery are similar to
other laparoscopic general surgery procedures
Outcomes of laparoscopic procedures in general surgical operations between 2006 and 2009
N
Utilization of
laparoscopy
LOS* (days)
Complications*
Mortality*
Bariatric surgery
54,885
90.0%
2.3 ± 2.8
6.3%
0.06%
Cholecystectomy
54,782
81.4%
3.3 ± 3.8
8.3%
0.18%
Antireflux surgery
8,339
79.3%
2.9 ± 4.3
10.7%
0.02%
Appendectomy
51,077
71.5%
1.6 ± 1.3
3.5%
0.02%
Colectomy
21,761
18.9%
5.6 ± 4.6
21.5%
0.54%
Ventral hernia repair
25,885
8.1%
3.2 ± 3.4
14.0%
0.24%
Rectal resection
2,392
7.4%
6.9 ± 5.1
25.0%
0.57%
Operations
* Outcome of laparoscopic operations; LOS: length of stay
Source: Nguyen B, Richardson JF, Smith B et al. Utilization of laparoscopy in general surgical
operations at academic centers. 2012 ASMBS Abstracts. PL-106.
34
Conclusions & Recommended Next
Steps
Conclusions
The evidence has shown that bariatric / metabolic surgery :
• Helped Type 2 diabetic patients achieve glycemic control more effectively than
intensive medical therapy within 1 year (STAMPEDE & Mingrone)
• Resolved or improved Type 2 diabetes and other obesity-related CV
comorbidities for up to 5 years (STAMPEDE, Buchwald, Klein and Bolen)
• Reduced medication use for Type 2 diabetes and other CV comorbidities for up
to 3 years (STAMPEDE, AHRQ/Segal and Klein)
• Was more efficient than usual care for the prevention of Type 2 diabetes in
persons with obesity at 15 years (Carlsson)
• Reduced the risk of cardiovascular death (myocardial infarction or stroke)
compared to customary intervention at 15 years (Sjostrom)
• Resulted in morbidity / mortality rates similar to well-established general
surgery procedures such as gallbladder surgery and hysterectomy (CMS)
• Is viewed an acceptable treatment option for obese patients with T2DM
(medical societies including the ADA, AHA, IDF, AACE & the Endocrine Society)
36
Next Steps – (Encourage referring physicians & PCPs …)
To recommend bariatric / metabolic surgery to selected obese
patients (BMI>35) with Type 2 diabetes to achieve better control of
their diabetes with much less medication:
o Rethink surgery as a therapeutic intervention, not just for severely
obese patients.
• Mode of action of bariatric surgery is metabolically analogous to many
T2DM medications with positive impact on GLP-1 & insulin sensitivity.
o Focus on those patients who are at highest risk of a CV event:
• Younger (under 60)
• Treated less than 10 years
• Difficulty maintaining glycemic control with metformin
• Having at least one other CV risk factor in addition to T2DM, e.g.
elevated insulin, hypertension and/or dyslipemia.
• Difficulty maintaining acceptable weight (almost all T2DM patients).
* Sources: Sjostrom, L and others. Bariatric Surgery and Long-term Cardiovascular Events. JAMA 2012; 307(1):56-65. and Berry, J.
and others. Lifetime Risks of Cardiovascular Disease. NEJM 2012; 366:321-29.
page 37
Discussion….
“What are your thoughts?”
Bariatric Surgery - Medical Society
Support
A growing consensus favors bariatric surgery
“Bariatric surgery should be considered for adults with BMI ≥
35 kg/m2 and type 2 diabetes, especially if the diabetes is
difficult to control with lifestyle and pharmacologic therapy.”
– American Diabetes Association (2009)
“When indicated, surgical intervention leads to significant
improvements in decreasing excess weight and comorbidities that can be maintained over time.”
– American Heart Association (2011)
“Bariatric surgery is an appropriate treatment for people with
type 2 diabetes and obesity not achieving recommended
treatment targets with medical therapies”
– International Diabetes Federation (2011)
“The beneficial effect of surgery on reversal of existing DM
and prevention of its development has been confirmed in a
number of studies”
– American Association of Clinical Endocrinologists (2011)
Sources: American Diabetes Association. Standards of medical care in diabetes – 2009. Diabetes Care 2009; 32(S1):S13-S61,
Poirier P, Cornier M-A, Mazzone T et al. Bariatric surgery and cardiovascular risk factors: A scientific statement from the American Heart Association. Circulation 2011; 123:00-00.
International Diabetes Federation. Bariatric surgical and procedural interventions in the treatment of obese patients with type 2 diabetes. 2011.
Handelsman Y, Mechanick JI, Blone L et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for developing a diabetes mellitus comprehensive plan. Endocr Prac 2011; 17(Suppl 2).
page 40
A growing consensus favors bariatric surgery
“The Endocrine Society recommends that practitioners
consider several factors in recommending surgery for
their obese patients with type 2 diabetes, including
patient’s BMI and age, the number of years of diabetes and
the assessment of the (patient’s) ability to comply with the
long-term lifestyle changes that are required to maximize
success of surgery and minimize complications.”
“… remission of diabetes, even if temporary, will still
lead to a reduction in the progression to secondary
complications of diabetes (such as retinopathy,
neuropathy and nephropathy), which would be an important
outcome of … surgery.”
– The Endocrine Society (March 2012)
Source: The Endocrine Society, Evaluating the Benefits of Treating Type 2 Diabetes with Bariatric Surgery, March 30, 2012.
page 41

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