Bariatric Surgery vs. Intensive Medical Bariatric Surgery vs. Intensive Medical Therapy in Obese Diabetic Patients: Therapy in Obese Diabetic Patients:

3-Year Outcome3-Year Outcomes

Philip R Schauer, Deepak L Bhatt, John P Kirwan, Kathy Wolski, Philip R Schauer, Deepak L Bhatt, John P Kirwan, Kathy Wolski, Stacy A Brethauer, Sankar D Navaneethan, Ali Aminian, Stacy A Brethauer, Sankar D Navaneethan, Ali Aminian,

Claire E Pothier, Ester SH Kim, Steve E Nissen, and Claire E Pothier, Ester SH Kim, Steve E Nissen, and Sangeeta R Sangeeta R KashyapKashyap

STAMPEDE investigatorsSTAMPEDE investigators

Results of the Results of the STAMPEDE TrialSTAMPEDE Trial

Cleveland ClinicCleveland ClinicBariatric and Metabolic InstituteBariatric and Metabolic Institute

Endocrinology, Diabetes and MetabolismEndocrinology, Diabetes and Metabolism

DisclosuresDisclosuresDisclosuresDisclosures

• Research support: Ethicon Endo-Surgery, NIH, American Research support: Ethicon Endo-Surgery, NIH, American Diabetes AssociationDiabetes Association

• Consulting and honoraria: Ethicon Endo-Surgery Consulting and honoraria: Ethicon Endo-Surgery

• STAMPEDE was funded by Ethicon Endo-Surgery, LifeScan STAMPEDE was funded by Ethicon Endo-Surgery, LifeScan Inc, Cleveland Clinic, and NIH-NIDDKInc, Cleveland Clinic, and NIH-NIDDK

BackgroundBackground• T2DM affects over 25 million individuals in the US, but < 50% T2DM affects over 25 million individuals in the US, but < 50%

of patients achieve adequate glycemic control on current of patients achieve adequate glycemic control on current pharmacotherapy. pharmacotherapy.

• Observational studies show improvement in glycemic control Observational studies show improvement in glycemic control and CV risk factors following bariatric surgery. and CV risk factors following bariatric surgery.

• Short-term (1-2 yrs.) RCTs, including the 1 year data of the Short-term (1-2 yrs.) RCTs, including the 1 year data of the STAMPEDE trial demonstrated remission of T2DM following STAMPEDE trial demonstrated remission of T2DM following bariatric surgery*.bariatric surgery*.

• However, no long-term However, no long-term ((>>3 yrs) RCT3 yrs) RCT data exist to compare data exist to compare the durability of bariatric surgery vs medical therapy for T2DM the durability of bariatric surgery vs medical therapy for T2DM control.control.

*Schauer P, Kashyap S, Wolski K. et al, NEJM 2012 366(17):1567-76

ObjectivesObjectives1)1) Compare the durability of bariatric surgery vs Compare the durability of bariatric surgery vs

medical therapy with respect to:medical therapy with respect to:

• Achieving biochemical resolution of T2DMAchieving biochemical resolution of T2DM

2) Compare differences between types of surgery 2) Compare differences between types of surgery

EndpointsEndpoints

Success rate of achieving HbA1c ≤ 6%Success rate of achieving HbA1c ≤ 6%PrimaryPrimary

SecondarySecondary

• Change in fasting plasma glucose (FPG)Change in fasting plasma glucose (FPG)

• Change in lipids, blood pressure, BMI Change in lipids, blood pressure, BMI

• Change in carotid intimal medial thicknessChange in carotid intimal medial thickness

• Change in medicationsChange in medications

• Safety and adverse eventsSafety and adverse events

• Quality of LifeQuality of Life

Intensive Medical TherapyIntensive Medical Therapy• Weight management with diet and lifestyle Weight management with diet and lifestyle

counseling per ADA clinical care guidelines*counseling per ADA clinical care guidelines*

• Insulin sensitizers, GLP-1 agonists, sulfonylureas Insulin sensitizers, GLP-1 agonists, sulfonylureas and multiple insulin injections utilized to target and multiple insulin injections utilized to target HbA1c ≤6%HbA1c ≤6%

• Scheduled visits with nutrition, psychology and Scheduled visits with nutrition, psychology and endocrinology per protocolendocrinology per protocol

• Follow-up visits every 3 months through year 2, and Follow-up visits every 3 months through year 2, and every 6 months for remaining follow upevery 6 months for remaining follow up

*Standards of medical care in diabetes--2011. Diabetes Care;34 Suppl 1:S11-61

Bariatric SurgeryBariatric Surgery

Roux-en-Y Gastric Bypass Sleeve GastrectomyRoux-en-Y Gastric Bypass Sleeve GastrectomyKashyap S, Schauer P, Bhatt D; Diabetes Obesity Metabolism2010 Sep;12(9):833

218 patients screened

50Intensive medical

therapy alone

50 Medical therapy

plussleeve gastrectomy

Population for 3-Year Analysis 40 48 49

150 randomized

STAMPEDE Trial: Flow of PatientsSTAMPEDE Trial: Flow of Patients

50Medical therapy

plusgastric bypass

1 withdrew consent prior to surgery

8 withdrew consent2 Lost to follow-up

• HbA1c >7.0%HbA1c >7.0%• BMI 27- 43 kg/mBMI 27- 43 kg/m22

• Age 20-60 yearsAge 20-60 years

91% retention

2 Lost to follow-up

Baseline CharacteristicsBaseline CharacteristicsBaseline CharacteristicsBaseline Characteristics

ParameterParameterMedical Medical TherapyTherapy(n=40)(n=40)

Bypass Bypass (n=48)(n=48)

SleeveSleeve (n=49) (n=49)

Age (yrs)Age (yrs) 50.350.3 48.048.0 47.847.8

FemalesFemales 67%67% 58%58% 78%78%

Duration of diabetes (yrs)Duration of diabetes (yrs) 8.88.8 8.08.0 8.38.3

HbA1c (%)HbA1c (%) 9.09.0 9.39.3 9.59.5

Body Mass Index (kg/mBody Mass Index (kg/m22)) 36.436.4 37.137.1 36.136.1

≥ ≥ 3 diabetes medications3 diabetes medications 61%61% 52%52% 46.9%46.9%

Insulin useInsulin use 51.2%51.2% 46%46% 44.9%44.9%

DepressionDepression 32%32% 37%37% 46%46%

Microvascular complicationsMicrovascular complications 20%20% 42%42% 29%29%

Note: Based on analyzed population

Primary and Secondary Endpoints at 36 MonthsPrimary and Secondary Endpoints at 36 MonthsPrimary and Secondary Endpoints at 36 MonthsPrimary and Secondary Endpoints at 36 Months

ParameterParameterMedical Medical Therapy Therapy (n=40)(n=40)

Bypass Bypass (n=48)(n=48)

Sleeve Sleeve (n=49)(n=49)

P P ValueValue11

P P ValueValue22

HbA1c ≤ 6% HbA1c ≤ 6% 5%5% 37.5%37.5% 24.5%24.5% <0.001<0.001 0.0120.012

HbA1c ≤ 6% HbA1c ≤ 6% (without DM meds)(without DM meds) 0%0% 35.4%35.4% 20.4%20.4% <0.001<0.001 0.0020.002

HbA1c ≤ 7% HbA1c ≤ 7% 40% 64.6% 65.3% 0.020.02 0.020.02

Change in FPG (mg/dL)Change in FPG (mg/dL) -6 -85.5 -46 0.0010.001 0.0060.006

Relapse of glycemic Relapse of glycemic controlcontrol 80%80% 23.8%23.8% 50%50% 0.030.03 0.340.34

% % change inchange in HDL HDL +4.6+4.6 +34.7+34.7 +35.0+35.0 <0.001<0.001 <0.001<0.001

% % change inchange in TG TG -21.5-21.5 -45.9-45.9 -31.5-31.5 0.010.01 0.010.01

% % change in change in CIMTCIMT 0.0480.048 0.0130.013 0.0170.017 0.360.36 0.490.49

1 Gastric Bypass vs Medical Therapy; 2 Sleeve vs Medical Therapy

0.0

-0.5

-1.0

-1.5

-2.0

-2.5

-3.0

-3.50 3 6 12 24 36

0.0

-0.5

-1.0

-1.5

-2.0

-2.5

-3.0

-3.50 3 6 12 24 36

Change in HbA1cChange in HbA1c

Change in HbA1c (%)

P<0.001

P<0.001

Value at Visit Baseline Month 6 Month 12 Month 24 Month 36Medical 9.0 (8.5) 7.1 (6.8) 7.5 (6.9) 7.7 (7.3) 8.4 (7.6)Gastric Bypass 9.3 (9.2) 6.3 (6.2) 6.3 (6.1) 6.5 (6.4) 6.7 (6.6)Sleeve 9.5 (8.9) 6.7 (6.4) 6.6 (6.4) 6.8 (6.8) 7.0 (6.6)

Value at Visit Baseline Month 6 Month 12 Month 24 Month 36Medical 9.0 (8.5) 7.1 (6.8) 7.5 (6.9) 7.7 (7.3) 8.4 (7.6)Gastric Bypass 9.3 (9.2) 6.3 (6.2) 6.3 (6.1) 6.5 (6.4) 6.7 (6.6)Sleeve 9.5 (8.9) 6.7 (6.4) 6.6 (6.4) 6.8 (6.8) 7.0 (6.6)

Medical

Sleeve Gastric Bypass

Medical

Sleeve Gastric Bypass

Change in Body Mass IndexChange in Body Mass Index

Changein BMI

(Kg/M2)

-12.0

-10.0

-8.0

-6.0

-4.0

-2.0

0.0

-12.0

-10.0

-8.0

-6.0

-4.0

-2.0

0.0

90 3 6 12 24 360 3 6 12 24 369

P=0.006

P<0.001

P<0.001

Value at Visit Baseline Month 6 Month 12 Month 24 Month 36Medical 36.4 34.6 34.2 35.0 34.8Gastric Bypass 37.1 28.2 26.7 27.3 27.9Sleeve 36.1 28.3 27.1 27.9 29.2

Value at Visit Baseline Month 6 Month 12 Month 24 Month 36Medical 36.4 34.6 34.2 35.0 34.8Gastric Bypass 37.1 28.2 26.7 27.3 27.9Sleeve 36.1 28.3 27.1 27.9 29.2

Medical

Sleeve Gastric Bypass

Medical

Sleeve Gastric Bypass

0

10

20

30

40

50

60

Baseline Month 3 Month 6 Month 12 Month 24 Month 360

10

20

30

40

50

60

Baseline Month 3 Month 6 Month 12 Month 24 Month 36

Percentage of Patients on InsulinPercentage of Patients on Insulin

% Patients% Patients

Medical 52 54 44 40 47 55Gastric Bypass 46 25 10 4 7 6Sleeve 45 16 6 8 9 8

Medical 52 54 44 40 47 55Gastric Bypass 46 25 10 4 7 6Sleeve 45 16 6 8 9 8

Medical

Sleeve Gastric Bypass

Medical

Sleeve Gastric Bypass

Cardiovascular Medications atCardiovascular Medications atBaseline and Month 36Baseline and Month 36

Cardiovascular Medications atCardiovascular Medications atBaseline and Month 36Baseline and Month 36

CV medications – number CV medications – number (%)(%)

Medical TherapyMedical Therapy(n=40)(n=40)

Bypass Bypass (n=48)(n=48)

SleeveSleeve (n=49) (n=49)

Baseline

NoneNone 0 (0)0 (0) 3 (6.3)3 (6.3) 2 (4.1)2 (4.1)

1 - 21 - 2 19 (47.5)19 (47.5) 17 (35.4)17 (35.4) 28 (57.1)28 (57.1)

>> 3 3 21 (52.5) 21 (52.5) 28 (58.3)28 (58.3) 19 (38.8)19 (38.8)

Month 36

NoneNone 1 (2.5)1 (2.5) 33 (68.8) *33 (68.8) * 21 (42.9) *21 (42.9) *

1 - 21 - 2 18 (45)18 (45) 14 (29.2)14 (29.2) 25 (51)25 (51)

>> 3 3 21 (52.5)21 (52.5) 1 (2.1)1 (2.1) 3 (6.1)3 (6.1)

* P value <0.05 with Medical Therapy group as comparator

Quality of Life

Physical Functioning

Role Limitations

Physical Health Components

Mental Health Components

** **

* <0.05 ** <0.001 (Compared to IMT)

**

*

*

%

%

Adverse Events through 36 MonthsAdverse Events through 36 MonthsAdverse Events through 36 MonthsAdverse Events through 36 Months

ParameterParameter Medical Therapy Medical Therapy (n=43)(n=43)

Bypass Bypass (n=50)(n=50)

Sleeve Sleeve (n=49)(n=49)

GI complicationsGI complications 2 (5)2 (5) 13 (26)13 (26) 5 (4)5 (4)

Re-opRe-op 00 2(4)2(4) 2(4)2(4)

StrokeStroke 00 00 1 (2)1 (2)

RetinopathyRetinopathy 00 1 (2)1 (2) 2 (4)2 (4)

NephropathyNephropathy 4 (9)4 (9) 7 (14)7 (14) 5 (10)5 (10)

Foot ulcersFoot ulcers 0 0 2 (4)2 (4) 1 (2)1 (2)

Excessive weight gainExcessive weight gain 7 (16)7 (16) 00 00

LimitationsLimitationsLimitationsLimitations

• Single-center trial – multicenter studies needed to Single-center trial – multicenter studies needed to determine if results can be generalized. determine if results can be generalized.

• Larger studies will need to determine potential Larger studies will need to determine potential benefit on cardiovascular events and diabetes benefit on cardiovascular events and diabetes related microvascular complications.related microvascular complications.

• Single-center trial – multicenter studies needed to Single-center trial – multicenter studies needed to determine if results can be generalized. determine if results can be generalized.

• Larger studies will need to determine potential Larger studies will need to determine potential benefit on cardiovascular events and diabetes benefit on cardiovascular events and diabetes related microvascular complications.related microvascular complications.

SummarySummarySummarySummary• Bariatric surgery was more effective than intensive medical Bariatric surgery was more effective than intensive medical

therapy in achieving glycemic control (HbA1c therapy in achieving glycemic control (HbA1c << 6.0%) with 6.0%) with weight loss as the primary determinant of this outcome. weight loss as the primary determinant of this outcome.

• Many surgical patients achieved glycemic control without use Many surgical patients achieved glycemic control without use of any diabetic medications (particularly insulin).of any diabetic medications (particularly insulin).

• Metabolic syndrome components (HDL, triglycerides, Metabolic syndrome components (HDL, triglycerides, glucose, BMI) showed greater improvement after surgery.glucose, BMI) showed greater improvement after surgery.

• Marked improvement in quality of life.Marked improvement in quality of life.

• Bariatric surgery was more effective than intensive medical Bariatric surgery was more effective than intensive medical therapy in achieving glycemic control (HbA1c therapy in achieving glycemic control (HbA1c << 6.0%) with 6.0%) with weight loss as the primary determinant of this outcome. weight loss as the primary determinant of this outcome.

• Many surgical patients achieved glycemic control without use Many surgical patients achieved glycemic control without use of any diabetic medications (particularly insulin).of any diabetic medications (particularly insulin).

• Metabolic syndrome components (HDL, triglycerides, Metabolic syndrome components (HDL, triglycerides, glucose, BMI) showed greater improvement after surgery.glucose, BMI) showed greater improvement after surgery.

• Marked improvement in quality of life.Marked improvement in quality of life.

ConclusionConclusionConclusionConclusion

Bariatric surgery (gastric bypass or sleeve Bariatric surgery (gastric bypass or sleeve gastrectomy) should be considered as a treatment gastrectomy) should be considered as a treatment option for patients with uncontrolled T2DM and option for patients with uncontrolled T2DM and moderate to severe obesity (BMI > 30 Kg/Mmoderate to severe obesity (BMI > 30 Kg/M22) with ) with results durable through 3 years of follow up.results durable through 3 years of follow up.

Bariatric surgery (gastric bypass or sleeve Bariatric surgery (gastric bypass or sleeve gastrectomy) should be considered as a treatment gastrectomy) should be considered as a treatment option for patients with uncontrolled T2DM and option for patients with uncontrolled T2DM and moderate to severe obesity (BMI > 30 Kg/Mmoderate to severe obesity (BMI > 30 Kg/M22) with ) with results durable through 3 years of follow up.results durable through 3 years of follow up.

Renal Outcomes through 36 MonthsRenal Outcomes through 36 MonthsRenal Outcomes through 36 MonthsRenal Outcomes through 36 Months