Cirurgia Metabólica - Solução ou Ilusão?

Cirurgia Metabólica: Solução ou ilusão ?

Tarissa Petry

Centro de Obesidade e Diabetes, Hospital Oswaldo Cruz , Sao Paulo, Brasil tpetry@haoc.com.br

Yes, I agree !!! • So far, T2DM is a primary medical disease

But ...

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How is T2DM today?

EASD, Berlin, 2012

NHANES data 2007-2010, n = 4,926 A1C < 7%

52.5%

BP < 130/80

51.1%

LDL < 100mg/dl 56.2% All 3

18.8%

Diabetes Care Publish Ahead of Print, published online March 6, 2013

• $ 246 BILLION in 2012 • 41% increase from previous estimate • 2.3 times higher than what expenditures would be in the absence of diabetes

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T2DM Treatment • Goals - Glycemic control and decrease microvascular complications and neuropathy - Macrovascular complications – Multifactorial approach

PREVENTION OF CV MORBIDITY AND MORTALITY

Impact of Intensive Therapy in CV outcomes & Big Clinical Trials Trial

Microvascul ar

CV events

Mortality

DCCT/EDIC

↓

↓

↔

↓

↔

UKPDS

↓

↓

↔

↓

↔

ACCORD

?

↔

↑

ADVANCE

↓

↔

↔

VADT

↔

↔

↔

UKPDS / UKPDS fu UK Prospective Diabetes Study (UKPDS) Group. Lancet.

1998;352:854-865.

Holman RR. N Engl J Med. 2008 Oct 9;359(15):1577-89 DCCT / EDIC DCCT Research Group. N Engl J Med 329;977-986, 1993 Nathan DM, et al. N Engl J Med. 2005;353:2643-2653.

ACCORD Gerstein HC, et al. N Engl J Med. 2008;358:2545-2559.

ADVANCE Patel A, et al. N Engl J Med. 2008;358:2560-2572.

VADT Duckworth W et al. N Engl J Med 2009;360

↔ ↓

Trials outcomes Long term F Up

Courtesy of JE Salles

A look back at Look AHEAD Friday, Oct. 19, 2012

• Weight loss does not lower heart disease risk from type 2 diabetes • Intervention stopped early in NIH-funded study of weight loss in overweight and obese adults with type 2 diabetes after finding no harm, but no cardiovascular benefits 8

Worldâ&#x20AC;&#x2122;s Bariatric/Metabolic Surgery 2015

55%

25%

18%

2%

Effect on Long-term Mortality Compared to Non-Operated Controls Study

Procedure

F/U

Mortality Reduction

MacDonald,1997

RYGB

9 yrs

88%

Flum, 2004

RYGB

4.4yrs

33%

Christou, 2004

RYGB

5 yrs

89%

Sowemimo, 2007

RYGB

4.4 yrs

50%

Oâ&#x20AC;&#x2DC;Brien, 2006

LAGB

12 yrs

73%

Adams, 2007

RYGB

8.4 yrs

40%

Sjostrom, 2007

VBG/other

14 yrs

31%

92% decrease in DM specific mortality

Do we have results reported?

Morbid Obese T2DM pts Hundreds of reports of case series of T2DM control after GI surgery in BMIs over 35!

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And BMIs lower than 35?

Cohen et al, 2012, 6 y F Up

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There are meta-analysis

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Weight and Type 2 Diabetes after Bariatric Surgery: Systematic Review and Meta-analysis 1990-2006; 19 studies, 4, 070 diabetic patients

The American Journal of Medicine (2009) 122, 248-256

Long term Longitudinal Studies SOS

X

• 2039 pts

2010 pts

• Followed for up to 20 years 15

SOS â&#x20AC;˘ Surgery puts T2DM in remission long term

Who recurred? Longstanding disease and older people Journal of Internal Medicine, 2013, 273; 219â&#x20AC;&#x201C;234 16

SOS • Surgery decreases long term incidence of T2DM

Journal of Internal Medicine, 2013, 273; 219–234

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SOS

Karlson, JAMA, 2014

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SOS

19

The RCTs

SURGERY OUTPERFORMS MED Tx IN ALL RCTs

Adapted from Cummings&Cohen The Lancet D&E, 2014

Surgery is safe !!!

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AHRQ Data: Bariatric Surgery Utilization and Outcomes in 1998 and 2004 1998

2004

% change

Number

13,386

121,055

804%

Inpatient death

0.89%

0.19%

-79%

Zhao. AHRQ: Jan 2007

Mortality Rates Following Common Operations in U.S. Hospitals Aortic

An eur

CABG

Craniot

Esophag

Hip

Res Rep ect lac

Panc

]

Ped.

He art Sur ger y

SRC: Bariatric Surgery Mortality 0.15% (155,567 Mortalit patients) Number of Hospitals performing operation

2485

National Average

3.9

y

1036 3.5

1600 10.7

1717 3445HG, Birkmeyer 1302 JD.458 Dmick JB, Welch Surgical mortality as an indicator of hospital quality. JAMA 2004,292, 847-851

9.1

0.3

8.3

5.4

Surgery is cost effective!!

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PlosOne, 2013

General medical expenditures in the diabetic cohort

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Use of diabetes medication before and after bariatric surgery by their primary care physicians

Makary, M. A. et al. Arch Surg 2010;145:726-731.

Copyright restrictions may apply.

Use of diabetes medication before and after bariatric surgery by their primary care physicians $10,592/yr

Makary, M. A. et al. Arch Surg 2010;145:726-731.

Copyright restrictions may apply.

Use of diabetes medication before and after bariatric surgery by their primary care physicians $10,592/yr

$1,878/yr

Makary, M. A. et al. Arch Surg 2010;145:726-731.

Copyright restrictions may apply.

Metabolic Surgery • Markedly reduced med use ( early post op) • Less hospital care for CV admissions • Cost effective • Less missing working days • Add cost saving to its positive health outcomes

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O que é Cirurgia Metabólica ?

•

Qualquer intervenção sobre o trato GI que controla o DM2 e outros componentes da síndrome metabólica, inicialmente através de mecanismos independentes da perda ponderal E perda de peso

Cirurgia metabólica NÃO É cirurgia para IMCs baixos!!

Original Use/Indication

Clinical Observations Additional/Unexpected Benefits

New Understanding Mechanisms of Action

Treatment Approved for Other Indications

PETRY & COHEN,in Wajchemberg, Endocrinologia 2014

What’s next?

• Which A1c targets are best?

– 6.0%, 6.5%, 7.0%

• Does it matter if target is reached with or without meds?

• Do we need further studies?

• Are there ongoing RCTs ?

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â&#x20AC;&#x153;Currently, any RCT to compare surgery x med Tx for T2DM should be considered unethical"

Rome, Oct 6, 2013 37

â&#x20AC;˘ RANDOMIZED CONTROLLED TRIALS TO: - Compare surgical techniques - Focus on timing for surgical indication ( the sooner the better??)

- How to select best candidates - Can surgery be the 1st option in selected cases?

- **Hard endpoints (microvascular disease) 29

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NIH-Sponsored Ongoing RCTs

• Type 2 Diabetes Patient Population – SLIMM-T2D (Goldfine, Lautz, et al.)

– Triabetes & Triabetes-2 (Courcoulas, et al.)

– CROSSROADS (Cummings, Flum, et al.)

– IDeaLS (Clark, Brancati, et al.)

– Stampede II (Kirwan, Schauer, Kashyap, et al.)

– SOLID (Sarwer, et al.)

• Obstructive Sleep Apnea Patient Population – ABC Trial (Patel, et al.)

•

Courtesy of DE Cummings

Non-NIH RCTs of Bariatric Surgery vs. Non-Surgical Rx (3)

NCT #

1231308

GLUCOSUR G

1257087

1821508

PRODIGIE S

Site

Design

Weill Cornell

RYGB, MM

Imperial College, UK

Intense v.

Conven Glu Ctrl Post-op

Oswaldo Cruz Brazil Catholic U., Chile

RYGB, MM

RYGB, VSG, MM

N

50

Start

“1999”

Inclusion

BMI

A1c 6.5-10

2835

100

Jan11

T2DM

72

Mar13

T2DM with µalb 30-300

150

Mar13

Microalb >30

26-35 Asian

3035

2835

Primary Endpoint

Notes

A1c < 6.5

CIMT Liver fat

1 yr

A1c < 6.0

Microvas c Complic s

2 yr

Urine Alb:Creat

Microvas c Complic s

F/U

2 yr

3 yr

Microalb regression

Microvas c Complic s

Courtesy of DE Cummings

And what about the Mega Intl RCT Surg X Med focusing on 10 years CV events and mortality?

• Should be powered to 5500 patients • Difficult to be accomplished • Drugs will eventually get better and critics will say that the comparison is not fair • Very, very expensive

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: Compare surgery + best med tx

x

Best med tx alone

In any endpoint!!

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OBRIGADO!! tpetry@haoc.com.br

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