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
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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 ? 36
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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