Remission of Diabetes after Bariatric Surgery: … › surgery › 2015BariatricMasters ›...

Remission of Diabetes after Bariatric Surgery: Results of Randomized Trials

Stacy Brethauer, MD Bariatric and Metabolic Institute

Cleveland Clinic Cleveland, OH

Disclosures

• Ethicon Endo-Surgery Speaker, Research

• Covidien Speaker

• EndoBetix Consultant

Bariatric Surgery Worldwide

Buchwald et al. Obes Surg Jan 2013

U.S. Bariatric Numbers Estimation

2011 2012 2013

Total 158,000 173,000 179,000

RNY 36.7% 37.5% 34.2%

Band 35.4% 20.2% 14%

Sleeve 17.8% 33% 42.1%

BPD/DS 0.9% 1% 1%

Revisions 6% 6% 6%

Other 3.2% 2.3% 2.7%

Bariatric Surgery vs. Intensive Medical

Therapy in Obese Diabetic Patients:

Philip R Schauer, Deepak L Bhatt, John P Kirwan, Kathy Wolski,

Stacy A Brethauer, Sankar D Navaneethan, Ali Aminian,

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

STAMPEDE investigators

3-Year Outcomes

of the STAMPEDE Trial

Cleveland Clinic Bariatric and Metabolic Institute

Endocrinology, Diabetes and Metabolism

Intensive Medical Therapy

• Weight management with diet and lifestyle

counseling per ADA clinical care guidelines*

• Insulin sensitizers, GLP-1 agonists, sulfonylureas

and multiple insulin injections utilized to target

HbA1c ≤6%

• Scheduled visits with nutrition, psychology and

endocrinology per protocol

• Follow-up visits every 3 months through year 2, and

every 6 months for remaining follow up

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

218 patients screened

50 Intensive medical

therapy alone

50 Medical therapy

plus sleeve gastrectomy

Population for 3-Year Analysis 40 48 49

150 randomized

STAMPEDE Trial: Flow of Patients

50 Medical therapy

plus gastric bypass

1 withdrew consent prior to surgery

8 withdrew consent 2 Lost to follow-up

• HbA1c >7.0%

• BMI 27- 43 kg/m2

• Age 20-60 years

91% retention

2 Lost to follow-up

Primary and Secondary Endpoints at 36 Months

Parameter

Medical

Therapy

(n=40)

Bypass

(n=48)

Sleeve

(n=49)

P

Value1

P

Value2

HbA1c ≤ 6% 5% 37.5% 24.5% <0.001 0.012

HbA1c ≤ 6%

(without DM meds) 0% 35.4% 20.4% <0.001 0.002

HbA1c ≤ 7% 40% 64.6% 65.3% 0.02 0.02

Change in FPG (mg/dL) -6 -85.5 -46 0.001 0.006

Relapse of glycemic

control 80% 23.8% 50% 0.03 0.34

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

% change in TG -21.5 -45.9 -31.5 0.01 0.01

% change in CIMT 0.048 0.013 0.017 0.36 0.49

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 HbA1c

Change in

HbA1c (%)

P<0.001

P<0.001

Medical

Sleeve

Gastric Bypass

V a l u e a t V i s i t B a s e l i n e M o n t h 6 M o n t h 1 2 M o n t h 2 4 M o n t h 3 6 M e d i c a l 9 . 0 ( 8 . 5 ) 7 . 1 ( 6 . 8 ) 7 . 5 ( 6 . 9 ) 7 . 7 ( 7 . 3 ) 8 . 4 ( 7 . 6 ) G a s t r i c B y p a s s 9 . 3 ( 9 . 2 ) 6 . 3 ( 6 . 2 ) 6 . 3 ( 6 . 1 ) 6 . 5 ( 6 . 4 ) 6 . 7 ( 6 . 6 ) S l e e v e 9 . 5 ( 8 . 9 ) 6 . 7 ( 6 . 4 ) 6 . 6 ( 6 . 4 ) 6 . 8 ( 6 . 8 ) 7 . 0 ( 6 . 6 )

V a l u e a t V i s i t B a s e l i n e M o n t h 6 M o n t h 1 2 M o n t h 2 4 M o n t h 3 6 M e d i c a l 9 . 0 ( 8 . 5 ) 7 . 1 ( 6 . 8 ) 7 . 5 ( 6 . 9 ) 7 . 7 ( 7 . 3 ) 8 . 4 ( 7 . 6 ) G a s t r i c B y p a s s 9 . 3 ( 9 . 2 ) 6 . 3 ( 6 . 2 ) 6 . 3 ( 6 . 1 ) 6 . 5 ( 6 . 4 ) 6 . 7 ( 6 . 6 ) S l e e v e 9 . 5 ( 8 . 9 ) 6 . 7 ( 6 . 4 ) 6 . 6 ( 6 . 4 ) 6 . 8 ( 6 . 8 ) 7 . 0 ( 6 . 6 )

Change in Body Mass Index

Change

in 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

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 Insulin

% Patients

Medical 52 54 44 40 47 55

Gastric Bypass 46 25 10 4 7 6

Sleeve 45 16 6 8 9 8

Medical

Sleeve

Gastric Bypass

Cardiovascular Medications at

Baseline and Month 36

CV medications – number

(%)

Medical Therapy

(n=40)

Bypass

(n=48)

Sleeve

(n=49)

Baseline

None 0 (0) 3 (6.3) 2 (4.1)

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

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

Month 36

None 1 (2.5) 33 (68.8) * 21 (42.9) *

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

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

* P value <0.05 with Medical Therapy group as comparator

Is Surgery Effective in Patients

with BMI < 35?

• Most Patients with T2DM have BMI 25-35 (60%)

•Currently Metabolic Surgery restricted to BMI ≥ 35

• STAMPEDE-36% of Patients with BMI <35

BMI < 35 vs. BMI ≥ 35

Change in HbA1c

BMI < 35 vs. BMI ≥ 35

Change in BMI

Quality of Life

Physical Functioning

Role Limitations

Physical Health Components

Mental Health Components

** **

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

**

*

*

%

%

Summary: QOL Changes

• Gastric Bypass: 5/8 domains improved

• Sleeve Gastrectomy: 2/8 domains improved

• Intensive Med Rx: 0/8 domains improved

Adverse Events through 36 Months

Parameter Medical Therapy

(n=43)

Bypass

(n=50)

Sleeve

(n=49)

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

Re-op 0 2(4) 2(4)

Stroke 0 0 1 (2)

Retinopathy 0 1 (2) 2 (4)

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

Foot ulcers 0 2 (4) 1 (2)

Excessive weight gain 7 (16) 0 0

Gastric Bypass vs Sleeve Gastrectomy

• Study not sufficiently powered to detect modest differences between RYGB and LSG

• Results favoring RYGB over LSG

– Greater success achieving A1c <7.0% without meds

– Greater reduction in DM and CV medications

– Greater reduction in wt. loss

– Greater improvement in Quality of life

• Results favoring LSG over RYGB - None

• 60 patient RCT LRYGB v LSG v IMT

• Baseline A1C 9.7%

• Mean BMI 37

• Beta cell function (mixed meal tolerance)

• Body composition

• 12 and 24 months

Stampede Metabolic Substudy BMI IMT

N=17 RYGB N=18

LSG N-19

P value IMT v RYGB

P value IMT v LSG

P value RYGB

v LSG

Baseline 35.8 36.1 36.4 0.74 0.57 0.77

24 Months 35.6 27.4 28.2 <0.001 <0.001 0.46

Change from Baseline

-0.2 -8.7 -8.2 <0.001 <0.001 0.66

Truncal Fat

Baseline 49.1 50.0 51.8 0.59 0.07 0.27

24 Months 50.0 34.1 41.7 <0.001 <0.001 0.006

Change from Baseline

0.9 -15.9 -10.1 <0.001 <0.001 0.04

Stampede Metabolic Substudy IMT N=17

RYGB N=18

LSG N=19

P value IMT v RYGB

P value IMT v LSG

P value RYGB v LSG

HbA1c < 6% 24 mos

1/17 (6%)

6/18 (33%)

2/19 (10%)

0.09 1.00 0.12

HbA1c Baseline

9.5 9.8 9.7 0.54 0.74 0.84

HbA1c 24 mos

8.4 6.7 7.1 0.01 0.04 0.18

FBG 24 mos (change from baseline)

134 (-33)

87 (-124)

104 (-70)

0.03 0.001

0.04 0.31

0.34 0.03

N using insulin 24 mos

10 (59%) 1 (6%) 2 (11%) 0.001 0.003 1.0

• Insulin Sensitivity (Matsuda Index) – 2.7-fold increase after RYGB

– 1.2-fold increase after LSG

– No change with IMT

• Pancreatic Hormonal Function (oral disposition index = secretion /resistance) – Markedly greater in RYGB compared to IMT

– Correlated with change in % of truncal fat

– No difference between LSG and IMT

Stampede Metabolic Substudy

• Incretin Responses

– Increased postprandial GLP-1 with RYGB, LSG

– GIP decreased in RYGB, no change with LSG



• Gastric bypass patients maintained near-normal glucose tolerance

• Associated with 5.8-fold increase in overall beta-cell function

• In gastric bypass pts, both insulin sensitivity and secrection increased

• Despite comparable weight loss in LSG, insulin sensitivity was only partially restored and beta cell function did not improve

NEJM 2012

Mingrone et al NEJM 2012

Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomised controlled trials Viktoria L Gloy et al. BMJ 2013;347:bmj.f5934

©2013 by British Medical Journal Publishing Group

Mean change in body weight (kg) after bariatric surgery versus non-surgical treatment

(control) for obesity.

Viktoria L Gloy et al. BMJ 2013;347:bmj.f5934


Type 2 diabetes remission after bariatric surgery versus non-surgical treatment (control) for

obesity.



Metabolic syndrome remission after bariatric surgery versus non-surgical treatment (control)

for obesity.



• This meta-analysis of randomised controlled trials provides summary effect estimates comparing bariatric surgery with non-surgical treatment for obesity on many different health outcomes

• Bariatric surgery is more effective in inducing body weight loss and remission of type 2 diabetes and metabolic syndrome. There were no perioperative deaths or cardiovascular events reported after bariatric surgery. The most common adverse events after bariatric surgery were iron deficiency anaemia (15%) and reoperations (8%)

• The lack of evidence beyond two years’ follow-up, in particular on adverse events, cardiovascular diseases, and mortality calls for further research

Conclusion

• Current randomized studies favor bypass procedures over sleeve for control of severe diabetes

• Weight loss outcomes vary, but medium-term outcomes favor RYGB and DS

• Metabolic effects: LSG < RYGB < DS

• Risk/Benefit analysis must still be patient-specific

Thank You

Remission of Diabetes after Bariatric Surgery: … › surgery › 2015BariatricMasters ›...

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