Congrés ADA 2012 Highlights AP Philadelphia 8-12 Juny 2012
F . X a v i e r C o s C l a r a m u n t CAP Sant Martí de Provençals. Barcelona RedGDPS / Primary Care Diabetes Europe
Congrés ADA 2012 Highlights
Sumari
Resum general del congrés www.diabetes.org
130 sessions (72 simposium) EADS/ADA, Lancet/ADA, IDF/ADA 377 Comunicacions orals 2578 Posters (presentats/publicats)
Congrés ADA 2012 Highlights
Sumari AP
State of the art ADA/EASD consensus Tractament
Anàlegs GLP-‐1 IDPPIV
Autoanalisis (si o no? !!!) Resultats finals dels estudis
-‐ DE-‐PLAN-‐CAT -‐ TINSAL -‐ TODAY -‐ ORIGIN
Management of Hyperglycemia in Type 2
Diabetes: A Patient-Centered Approach
Position Statement of the American Diabetes Association (ADA) and ���the European Association for the Study of Diabetes (EASD)
ADA-EASD Position Statement: Management of Hyperglycemia in T2DM: A Patient-Centered
Approach
1. PATIENT-‐CENTERED APPROACH
2. BACKGROUND • Epidemiology and health care impact • RelaDonship of glycemic control to outcomes • Overview of the pathogenesis of Type 2 diabetes
3. ANTI-‐HYPERGLYCEMIC THERAPY • Glycemic targets • TherapeuDc opDons
-‐ Lifestyle -‐ Oral agents & non-‐insulin injectables -‐ Insulin
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
3. ANTIHYPERGLYCEMIC THERAPY • ImplementaDon Strategies
-‐ IniDal drug therapy -‐ Advancing to dual combinaDon therapy -‐ Advancing to triple combinaDon therapy -‐ TransiDons to and DtraDons of insulin
4. OTHER CONSIDERATIONS • Age • Weight • Sex/racial/ethnic/geneDc differences • ComorbidiDes (Coronary artery disease, Heart failure,
Chronic kidney disease, Liver dysfunc8on, Hypoglycemia)
5. FUTURE DIRECTIONS / RESEARCH NEEDS
ADA-EASD Position Statement: Management of Hyperglycemia in T2DM: A Patient-Centered
Approach
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Initial drug monotherapy
Efficacy (! HbA1c) Hypoglycemia Weight Side effects Costs
Healthy eating, weight control, increased physical activity
Metformin high low risk neutral/loss GI / lactic acidosis low
If needed to reach individualized HbA1c target after ~3 months, proceed to 2-drug combination (order not meant to denote any specific preference):
Metformin +
Metformin +
Metformin +
Metformin +
Metformin +
Efficacy (! HbA1c) Hypoglycemia Weight Major side effect(s) Costs
high low risk gain edema, HF, fx’s‡ high
Thiazolidine- dione
intermediate low risk neutral rare‡
high
DPP-4 Inhibitor
highest high risk gain hypoglycemia‡
variable
Insulin (usually basal)
Two drug combinations*
Sulfonylurea† +
Thiazolidine-dione +
DPP-4 Inhibitor +
GLP-1 receptor agonist +
Insulin (usually basal) +
Metformin +
Metformin +
Metformin +
Metformin +
Metformin +
TZD
DPP-4-i
GLP-1-RA
Insulin§
SU†
DPP-4-i
GLP-1-RA
Insulin§
SU† SU†
TZD TZD
TZD
DPP-4-i
Insulin§ Insulin§
If combination therapy that includes basal insulin has failed to achieve HbA1c target after 3-6 months, proceed to a more complex insulin strategy, usually in combination with 1-2 non-insulin agents:
Insulin# (multiple daily doses)
Three drug combinations
More complex insulin strategies
or
or
or
or
or
or
or
or
or
or
or
or GLP-1-RA
high low risk loss GI‡ high
GLP-1 receptor agonist
Sulfonylurea†
high moderate risk gain hypoglycemia‡ low
If needed to reach individualized HbA1c target after ~3 months, proceed to 3-drug combination (order not meant to denote any specific preference):
T2DM AnDhyperglycemic Therapy: General RecommendaDons
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Initial drug monotherapy
Efficacy (! HbA1c) Hypoglycemia Weight Side effects Costs
Healthy eating, weight control, increased physical activity
Metformin high low risk neutral/loss GI / lactic acidosis low
If needed to reach individualized HbA1c target after ~3 months, proceed to 2-drug combination (order not meant to denote any specific preference):
Metformin +
Metformin +
Metformin +
Metformin +
Metformin +
Efficacy (! HbA1c) Hypoglycemia Weight Major side effect(s) Costs
high low risk gain edema, HF, fx’s‡ high
Thiazolidine- dione
intermediate low risk neutral rare‡
high
DPP-4 Inhibitor
highest high risk gain hypoglycemia‡
variable
Insulin (usually basal)
Two drug combinations*
Sulfonylurea† +
Thiazolidine-dione +
DPP-4 Inhibitor +
GLP-1 receptor agonist +
Insulin (usually basal) +
Metformin +
Metformin +
Metformin +
Metformin +
Metformin +
TZD
DPP-4-i
GLP-1-RA
Insulin§
SU†
DPP-4-i
GLP-1-RA
Insulin§
SU† SU†
TZD TZD
TZD
DPP-4-i
Insulin§ Insulin§
If combination therapy that includes basal insulin has failed to achieve HbA1c target after 3-6 months, proceed to a more complex insulin strategy, usually in combination with 1-2 non-insulin agents:
Insulin# (multiple daily doses)
Three drug combinations
More complex insulin strategies
or
or
or
or
or
or
or
or
or
or
or
or GLP-1-RA
high low risk loss GI‡ high
GLP-1 receptor agonist
Sulfonylurea†
high moderate risk gain hypoglycemia‡ low
If needed to reach individualized HbA1c target after ~3 months, proceed to 3-drug combination (order not meant to denote any specific preference):
T2DM AnDhyperglycemic Therapy: General RecommendaDons Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Initial drug monotherapy
Efficacy (! HbA1c) Hypoglycemia Weight Side effects Costs
Healthy eating, weight control, increased physical activity
Metformin high low risk neutral/loss GI / lactic acidosis low
If needed to reach individualized HbA1c target after ~3 months, proceed to 2-drug combination (order not meant to denote any specific preference):
Metformin +
Metformin +
Metformin +
Metformin +
Metformin +
Efficacy (! HbA1c) Hypoglycemia Weight Major side effect(s) Costs
high low risk gain edema, HF, fx’s‡ high
Thiazolidine- dione
intermediate low risk neutral rare‡
high
DPP-4 Inhibitor
highest high risk gain hypoglycemia‡
variable
Insulin (usually basal)
Two drug combinations*
Sulfonylurea† +
Thiazolidine-dione +
DPP-4 Inhibitor +
GLP-1 receptor agonist +
Insulin (usually basal) +
Metformin +
Metformin +
Metformin +
Metformin +
Metformin +
TZD
DPP-4-i
GLP-1-RA
Insulin§
SU†
DPP-4-i
GLP-1-RA
Insulin§
SU† SU†
TZD TZD
TZD
DPP-4-i
Insulin§ Insulin§
If combination therapy that includes basal insulin has failed to achieve HbA1c target after 3-6 months, proceed to a more complex insulin strategy, usually in combination with 1-2 non-insulin agents:
Insulin# (multiple daily doses)
Three drug combinations
More complex insulin strategies
or
or
or
or
or
or
or
or
or
or
or
or GLP-1-RA
high low risk loss GI‡ high
GLP-1 receptor agonist
Sulfonylurea†
high moderate risk gain hypoglycemia‡ low
If needed to reach individualized HbA1c target after ~3 months, proceed to 3-drug combination (order not meant to denote any specific preference):
T2DM AnDhyperglycemic Therapy: General RecommendaDons Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Initial drug monotherapy
Efficacy (! HbA1c) Hypoglycemia Weight Side effects Costs
Healthy eating, weight control, increased physical activity
Metformin high low risk neutral/loss GI / lactic acidosis low
If needed to reach individualized HbA1c target after ~3 months, proceed to 2-drug combination (order not meant to denote any specific preference):
Metformin +
Metformin +
Metformin +
Metformin +
Metformin +
Efficacy (! HbA1c) Hypoglycemia Weight Major side effect(s) Costs
high low risk gain edema, HF, fx’s‡ high
Thiazolidine- dione
intermediate low risk neutral rare‡
high
DPP-4 Inhibitor
highest high risk gain hypoglycemia‡
variable
Insulin (usually basal)
Two drug combinations*
Sulfonylurea† +
Thiazolidine-dione +
DPP-4 Inhibitor +
GLP-1 receptor agonist +
Insulin (usually basal) +
Metformin +
Metformin +
Metformin +
Metformin +
Metformin +
TZD
DPP-4-i
GLP-1-RA
Insulin§
SU†
DPP-4-i
GLP-1-RA
Insulin§
SU† SU†
TZD TZD
TZD
DPP-4-i
Insulin§ Insulin§
If combination therapy that includes basal insulin has failed to achieve HbA1c target after 3-6 months, proceed to a more complex insulin strategy, usually in combination with 1-2 non-insulin agents:
Insulin# (multiple daily doses)
Three drug combinations
More complex insulin strategies
or
or
or
or
or
or
or
or
or
or
or
or GLP-1-RA
high low risk loss GI‡ high
GLP-1 receptor agonist
Sulfonylurea†
high moderate risk gain hypoglycemia‡ low
If needed to reach individualized HbA1c target after ~3 months, proceed to 3-drug combination (order not meant to denote any specific preference):
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Basal insulin only (usually with oral agents)
Basal insulin + 1 (meal-time) rapid-acting insulin injection
Basal insulin + !2 (meal-time) rapid-acting insulin injections
Premixed insulin twice daily
less flexible
Number of injections
1
Flexibility
Regimen complexity
low
mod.
Non-insulin regimens
Sequential Insulin Strategies in T2DM Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Congrès ADA 2012 Highlights
http://www.diabetes.conference-companion.com
Congrés ADA 2012 Highlights
Nou consens ADA/EASD del tractament de la hiperglicemia en la Diabetes tipus 2
State of the art lecture Dr. Silvio Inzucchi
Cal individualitzar el tractament hipoglicemiant i els objectius terapeutics
Alimentació, activitat fisica i educació són la base del tractament
Metformina és el farmac de primera elecció si no està contraindicat
Després de Metformina cal valorar tractament combinat 1-2 FFOO/ SC.
Prioritzar minimitzar Efectes secundaris
Caldria plantejar-se decisions terapeutiques compartides
(preferències,necesitats i valors)
La reducció de RCV hauria de ser la prioritat en el tractament
Congrés ADA 2012 Highlights
IN CRE TINES
Actividad GLP-1 y GIP
Secreción de incretinas
Tracto GI
Comida
Pancreas
Cel Beta Cel Alfa
Reducción de la glucemia
Captación de glucosa por Musculo y Tejido adiposo
Insulina Cel beta
(GLP-1 y GIP) Glucosa dependiente
metabolitos
GLP-1 y GIP
X Inhibidor DPP-4
Incretin miméticos
Enzima DPP-4
Drucker DJ. Diabetes Care. 2003;26:2929–40.
ä Glucagon Cel alfa (GLP-1) Glucosa
dependiente
ä Producción hepática de glucosa
Us clínic de les Incretines
Congrés ADA 2012 Highlights
IN CRE TINES Anàlegs receptor GLP-1 Incretin miméticos
Congrés ADA 2012 Highlights
A C multicentric aleatoritzat Glimepiride vs Exenatide en pacients DM2 mal controlats en monoterapia amb Metformina Avaluació: HbA1c > 9% els primers 3 mesos o >7% en dues ocasions passats 6 mesos N= 1029 DM2 mal control MET Edat: 56 (10) anys Sexe: 56% homes IMC: 32.6 kg/m2 HbA1c: 7.5 %
EUREXA trial ADA/Lancet Dr. Schernthaner
Congrés ADA 2012 Highlights
EUREXA trial ADA/Lancet Dr. Schernthaner
1. AC més llarg amb Anàleg GLP1 (4.5 anys) 2. Millor control HbA1c, reducció de pes i menys Hipoglucemies en
el grup Exenatide. 3. 4-5 de cada 10 pacients van necesitar afegir un altre farmac per
mantenir el control metabolic
Congrés ADA 2012 Highlights
Analegs del GLP 1 Are they all the same? Dr. Filip Knop Dinamarca
• Categoritzacio per:
• FK
• Estructura
• Tamany
FK Curta durada Llarga durada Molecules Exenatide1
Lixisenatide1 Exenatide LAR1 Liraglutide2 Albuglutide2
Impacte glicèmic G. Post prandial G. Basal Nausea +++ ++
1. Estructura similar a Exedin 4 2. Estructura similar a GLP1
No són similars
Congrés ADA 2012 Highlights
Analegs del GLP 1 Tenen impacte CV?? Dr. Steven Marso . Cardioleg (Kansas)
Existencia de receptors GLP1 pancrees endocrí, cardiomiocit i
endoteli vascular
Recerca en models animals i humans
Beneficis en xifres PA i lipids
Models experimentals en IAM i I Cardiaca
Congrés ADA 2012 Highlights
EASIE trial ADA/Lancet Dr. Pablo Aschner ( Colombia)
A C multicentric aleatoritzat obert I. Glargine I Sitagliptina en pacients DM2 mal controlats en monoterapia amb Metformina Objectiu: comparar eficacia (HbA1c), tolerabilitat i seguretat d’ambdos molecules N = I. Glargina: 250 Sitagliptina: 265 Duració: 24 setmanes Edat: 53.6 (9) anys Sexe: 51% homes IMC: 31.1 kg/m2 Duració DM2: 4.5 anys HbA1c: 8.5 %
Dosis Sitagliptina 100 mg/d
Dosis insulina final del estudi 0.5UI/kg/dia
Congrés ADA 2012 Highlights
EASIE trial ADA/Lancet Dr. Pablo Aschner ( Colombia)
Despres de 24 setmanes I. Glargina Sitagliptina
HbA1c < 7% 68% 42% p< 0.0001
Hipoglucemia (pacient/any) 4.21 0.50 p< 0.0001
Congrés ADA 2012 Highlights
DPP4 Inh Are they all the same? Dr. Adrian Vella ( Mayo Clinic) USA
Tenen estructures quimiques diferents
Comparteixen el mateix mecanisme d’acció amb similar inh
enzimatica ( 80%)
Existeixen diferencies en la seva FK
Reduccio HbA1c 0.7% aprox
Baix risc Hipoglicemia
No increment de pes
Efectes adversos similars
Si, són similars
Congrés ADA 2012 Highlights
Debat: AGC si o no????
Pro Dr. Lutz Heinemann (Germany)
- MA i RS AGC es relaciona reduc. de HbA1c de 0.2 a 0.4
- Estudis amb limitacions (randomització, entrenament ,…)
- M. Franciosi et al. Diabetic Med 2011;28:798 reduc.
HbA1c 0.5%
- Eina d’empoderament del pacient en l’autocontrol
Congrés ADA 2012 Highlights
Debat: AGC si o no????
Contra Dr. Jeffrey Stephens (UK)
- Argumenta que les reduccions d’HbA1c observades no
són clinicament rellevants.
- Excepció per els diabètics de recent diagnostic amb valors
HbA1c més elevats
- Importancia en que cal saber fer la tecnica i tambe
ENTENDRE els resultats i actuar en consequencia
- Apropiat en pacients amb risc de HIPOS i de forma
transitoria (canvi de tractament o malaltia intercorrent)
Delay in Progression to Type 2 Diabetes among High-Risk Spanish Individuals DE-PLAN-CAT study
Delay in Progression to Type 2 Diabetes among High-Risk Spanish Individuals Following Lifestyle Intervention in Real-Life Primary Care DE-PLAN CAT study Diabetes in Europe - Prevention using Lifestyle, Physical Activity and Nutritional intervention
XAVIER COS1, BERNADO COSTA1, FRANCISCO BARRIO1, JOAN J. CABRÉ1, JOSEP LLUIS PIÑOL1, SONIA SARRET1, CLAUSTRE SOLÉ1, XAVIER MUNDET1, TERESA MUR1, MONTSERRAT COT1, JACINT CAULA1, FRANCESC PUJOL1, JAANA LINDSTRÖM2, JAAKKO TUOMILEHTO2, DE-PLAN-CAT RESEARCH GROUP1 1Primary Care University reasearch institute. IDIAP Jordi Gol. Barcelona, Spain 2Department of Public Health, University of Helsinki, Finland
Área de Investigación en Diabetes y Enfermedades Endocrino-Metabólicas Prevencion de Diabetes Research Agenda (IDIAP Jordi Gol) .
The DE-PLAN study (2004) DE - PLAN CAT (2005) Diabetes in Europe - Prevention using Lifestyle, Physical Activity and Nutritional intervention Financiacion de la UE (DG SANCO), FIS (Instituto de Salud Carlos III) y Departamento de Salut Publica de la Generalitat de Catalunya
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
DE PLAN DE PLAN-CAT
0
5
10
15
20
25
30
35
Year 1 Year 2 Year 3 Year 4
Standard care GroupIntensive GroupComplete Group
Años 1 2 3 4 Grupo Standard 20 (6) 41 (12.3) 53 (15.9) 61 (18.3) Standard-Care Intervention Group 17 (7.8) 37 (16.9) 51 (23.3) 63 (28.8) No acumulado de diabetes 37 (6.7) 78 (14.1) 104 (18.8) 124 (22.5)
Incidencia acumulada de Diabetes
La incidencia de diabetes tras una mediana de 4,2 años fue 7,2 y 4,6 casos-100 personas-año (RRR=36,5%; p<0,005)
Resultados 2
Participantes a riesgo Año 1 Año 2 Año 3 Año 4 Total no. 514 476 453 430 N. Acumulado de pacientes diabetes 37 78 104 124 Grupo Intensivo 20 41 53 61 Grupo Standard 17 37 51 63
4 3 2 1 0
0.9
0.8
0.7
0
1.0
Follow-up time (years) p = 0.005 (Log Rank)
Cum
ulat
ive
prob
abili
ty o
f rem
aini
ng d
iabe
tes-
free
NNT = 9.5
El número necesario de participantes a tratar durante 4 años para reducir un caso de diabetes fue 9,5.
Resultados 3
1. Se observa una reduccion del 36% en la incidencia de in Diabetes
2. Todos los participantes mostraron beneficios de la Intervencion en
estilos de vida, independientemente de la edad y el sexo.
3. Es necesario tratar 10 individuos de alto riesgo durante 4 años con un programa de educacion de 6 horas para evitar (prevenir or
retrasar) 1 caso de diabetes.
4. Es posible conseguir una reduccion de la incidencia de Diabetes en sujetos de alto riesgo con intervenciones de estilos de
vida en el ambito de la Atencion Primaria.
Conclusiones
Congrés ADA 2012 Highlights
TINSAL trial Dr. Allison Goldfine (Joslin Diabetes Center)
Congrés ADA 2012 Highlights
TINSAL trial Dr. Allison Goldfine (Joslin Diabetes Center)
A C multicentric aleatoritzat salsalat 3.5 gr/d o PCB 48 set Objectiu: Canvi de la HbA1c Criteris inclusió
Edat 18 a 75 anys DM2 en FFOO A1c 7-9.5%
Criteris Exclusió Tt. Amb Glitazones, Insulina o Analegs GLP 1 Tt. Crònic amb AINES FG< 60 ml/min
N= 286 DM2 no controlada
Congrés ADA 2012 Highlights
TINSAL trial resultats Dr. Allison Goldfine (Joslin Diabetes Center)
N= 286 Edat: 56(10) anys Sexe: 55% homes IMC: 33.3 kg/m2 HbA1c: 7.7(0.7) % Met 88% Secretagog 82% (mono 41% bi 49% tri 6%) Aspirina 41% Estatines 60%
Despres de 48 setmanes Reducció HBA1C 0.24% (Salsalat vs PCB) p< 0.001
Reducció de Leucocits (Neutròfils i Limfòcits)
No canvis Prot C Reactiva
Reducció del aclariment insulina hepàtic
Canvis perfil lipidic (é Col total i LDL c, ê TG ) p< 0.02 1. Aquest estudi permet afirmar que la hipotesis inflamatoria pot tenir un paper en la fisiopatologia de la DM2
2. El Salsalat no es pot considerar un tractament per la DM2
Congrés ADA 2012 Highlights
TODAY trial Dr. Philip Zeitler (University of Colorado)
Opcions terapeutiques en pacients diabetics tipus 2 adolescents o joves Criteris inclusió
Edat 10 a 17 anys DM2 < 2 anys evolució IMC > percentil 85 Ac’s antipancreàtics neg /C peptit > 0.6 ng/ml
15 centres N= 699 (Edat 14 anys, IMC 34.9 kg/m2, 7.8 mesos desde Dx DM2) 3 grups de intervenció: Met, Met + Rosigli i Met+SV
Congrés ADA 2012 Highlights
TODAY trial resultats Dr. Philip Zeitler (University of Colorado)
Inici del estudi - 26% HTA - 13% mircoalbuminuria - 80% HDL-c baixa - 10% TG elevats - nivell SE i educacio pares baix
End point A1c > 8% 6 mesos o descompensacio metabolica persistent
Seguiment 3.9 anys Raons per End point similars a tots els grups.
IMC no va influenciar en els resultats
- Metformina menys efectiva en pacients de color - > 50% no van aconseguir control glicemic amb Met - Important deteriorament funcionalisme β
The Big Picture - ORIGIN • A large international RCT in people with new or
recently diagnosed diabetes, IFG or IGT & additional CV risk factors lasting > 6 years
• Assessed the effect of 2 independent therapies on serious CV outcomes in > 12,500 people: a) titrated basal insulin using insulin glargine b) 1 g of omega 3 FA
ORIGIN Research Questions
In high risk people with IFG, IGT or early diabetes,
a) does insulin replacement therapy targeting fasting normoglycemia (< 5.3 mM or 95 mg/dl) with insulin glargine, reduce CV outcomes more than standard approaches to dysglycemia?
b) does adding omega 3 FA reduce CV death?
Participants (Key Inclusion Criteria) • Age > 50 yrs AND
• Dysglycemia AND – EITHER IFG or IGT or new type 2 DM by OGTT
[i.e. FPG > 110 (6.1); or 2 Hr PG > 140 (7.8)] – OR prior type 2 DM @ stable dose > 10 wks & …
• on no OADs … + HbA1c < 9.0% • < half-max 1 OAD + HbA1c < 8.5% • > half-max 1 OAD + HbA1c < 8.0%
• High CV Risk – EITHER Prior MI, stroke, revasc, angina + doc. ischemia – OR MA, proteinuria, LVH, 50% art. stenosis, ABI < 0.9
Glargine Standard Care Omega 3 FA* Glargine + Omega 3 Omega 3
Placebo Glargine + Placebo Placebo
ORIGIN Factorial Design N=12,537; 573 sites; 40 countries; 2 Comparisons
Recruitment: Sept ‘03 – Dec’05 Final Visit: Q4 2011 Median (IQR) Follow-up: 6.2 y (5.8-6.6)
Glargine (Lantus): open vs. standard care Omega 3 FA (Omacor): double-blind; 1 cap/day*
*Omacor contains EPA 465 mg & DHA 375 mg
Major Outcomes: Glargine Trial Primary • CV death OR MI OR stroke • CV death OR MI OR stroke OR revasc OR CHF hosp’n
Secondary • Microvascular composite
(i.e. doubling of serum Cr, progression of albuminuria category, dialysis/renal transplant, laser Rx/vitrectomy for retinopathy)
• New type 2 diabetes (in those without baseline diabetes) • All cause death
• Cancers • Angina, amputation for ischemia, • CV & other hospitalizations • Hypoglycemia, weight • Cognition • Erectile dysfunction
Other Outcomes & Measures
Spain
Norway
PortugalTurkey
Ukraine
Greece
Ireland
Greenland
Iceland
United States
Canada
MexicoThe Bahamas
Cuba
Panama
El Salvador Nicaragua
Costa Rica
JamaicaHaiti
Dom. Rep.
Argentina
Bolivia
Colombia
Venezuela
Peru
Brazil
Guyana
Chile
EcuadorKenya
Ethiopia
EritreaSudan
Egypt
NigerMauritania
Mali
Nigeria
Somalia
Namibia
Libya
Chad
TanzaniaDem. Rep.Of Congo
Angola
Algeria
Madagascar
Zambia
Gabon
Tunisia
Morocco
SwazilandLesotho
Liberia
Sierra Leone
GuineaGambia
Congo
Senegal
Guinea Bissau
IsraelLebanon
Georgia Kyrgyzstan
Yemen
IraqIran
Oman
Saudi Arabia
Russia
India
China
Kazakhstan
Nepal
Vietnam
Sri Lanka
PapuaNew
Guinea
Brunei
Philippines
Malaysia
Indonesia
Japan
Mongolia
S. KoreaN. Korea
Australia
New Zealand
United Kingdom
FijiZimbabwe
Vanuatu
Uzbekistan
Uruguay
U.A.E.
Uganda
Turkmenistan
Togo
Thailand
Tajikistan
Syria
Sweden
Suriname
South Africa
Antarctica
Solomon Islands
Sao Tome & Principe
Rwanda
Qatar
Poland
Paraguay
Pakistan
Neth.
Mozambique
Laos
Kuwait
HondurasGuatemala
Ghana
Germany
French Guiana
France
Finland
Equatorial Guinea
Dijbouti
Denmark
Cyprus
Coted'Ivoire Central African Republic
Cape Verde
Cameroon
Cambodia
Burundi
Burkina Faso
Bulgaria
Botswana
Bhutan
Benin
Belize
Bangla-desh
Azerb.
Afghanistan
Western Sahara(Occupied by Morocco)
Timor Leste (East Timor)
Myanmar(Burma)
ATLANTIC
PACIFIC
PACIFIC
INDIAN
OCEAN
OCEAN
OCEAN
OCEAN
Bel.Belarus
HungaryRomaniaSwitz.
Italy
Jordan
Randomized By Region N=12537 from 573 sites in 40 countries
N. America 1314 (11%) Europe/Africa 6060 (48%) Australia 202 (2%)
S. America 3853 (31%) Asia 1108 (9%)
Characteristic % Drug Use %
Smoking 12 Statin 54
Hypertension 80 ACE-I/ARB 69
Any Albuminuria 15 Thiazide 19
Previous CVD 59 Beta Blocker 53
Other BP Drug 41
Antiplatelet 69
Baseline Characteristics Mean Age = 63.5 yrs; Females = 35%
Conventional Units
SI Units
BMI (kg/m2) 29.8 29.8 Blood Pressure (mm) 146/84 146/84
Cholesterol (mg/dl or mM) 190 4.9 LDL (mg/dl or mM) 112 2.90 HDL (mg/dl or mM) 46 1.19 TG (Median mg/dl or mM) 140 1.58
Baseline Characteristics (Mean Level)
Interventions (Added to Lifestyle) • Insulin Glargine Group
– Same approach for people with/without DM – Add evening glargine to 0 or 1 oral agent – Self-titrate @ 1-2 units, 2/wk; target capillary FPG < 95
mg/dl (5.3 mM) – Metformin could be added to mitigate hypoglycemia
• Standard Care Group – Non-DM Screen for DM yearly – DM Guideline-based + MD’s judgment
No insulin until > 2 OADs & no glargine
Median A1C Levels
IQR 5.5 – 6.5
IQR 5.8 – 6.9
Insulin Glargine
Standard Care
P
Cholesterol (mg/dl) 175 177 0.09 LDL (mg/dl) 102 102 0.51 HDL (mg/dl) 45 46 <0.001 Triglyceride (mg/dl) 124 128 <0.001
HR 69.2 69.7 0.08 SBP/DBP 141/79 141/79 0.4
Final CV Risk Factors ConventionaI Units
Years of Follow-up
Prop
ortio
n w
ith e
vent
s
0.0
0.1
0.2
0.3
0.4
0.5
0 1 2 3 4 5 6 7
GlargineStandard Care
# at Risk 1 2 3 4 5 6 7
G
SC
6264 6057 5850 5619 5379 5151 3611 766
6273 6043 5847 5632 5415 5156 3639 800
Time to Adjudicated Primary Outcome 1 - CV Death MI Stroke
Adj. HR 1.02 (0.94, 1.11) Log Rank P = 0.63
1st Co-primary: MI, Stroke, or CV Death
Years of Follow-up
Prop
ortio
n w
ith e
vent
s
0.0
0.1
0.2
0.3
0.4
0.5
0 1 2 3 4 5 6 7
GlargineStandard Care
# at Risk 1 2 3 4 5 6 7
G
SC
6264 5827 5474 5153 4835 4523 3076 631
6273 5833 5493 5186 4880 4555 3142 663
Time to Adjudicated Primary Outcome 2 - CV Death-MI-Stroke-HF Hosp-Revasc
Adj. HR 1.04 (0.97, 1.11) Log Rank P = 0.27
2nd Co-Primary: MI, Stroke, CV Death, Revascularization, Heart Failure
Years of Follow-up
Prop
ortio
n w
ith e
vent
s
0.0
0.1
0.2
0.3
0.4
0.5
0 1 2 3 4 5 6 7
GlargineStandard Care
# at Risk 1 2 3 4 5 6 7
G
SC
6264 6150 6024 5857 5687 5508 3906 847
6273 6159 6029 5878 5710 5501 3931 878
Time to Adjudicated All Death
Adj. HR 0.98 (0.90, 1.08) Log Rank P = 0.70
All-cause Death
Summary of Findings
• 1st CV Composite: HR = 1.02 (0.94, 1.11)
• 2nd CV Composite: HR = 1.04 (0.97, 1.11)
• Microvascular Composite: HR = 0.97 (0.90, 1.05)
• Death: HR = 0.98 (0.90, 1.08)
• Cancer: HR = 1.00 (0.88, 1.13)
• Conversion IFG/IGT to DM: HR = 0.72 (0.58, 0.91) P=0.006
ORIGIN clearly assessed the effect of basal insulin glargine on important health outcomes:
Summary of Findings Compared to standard glycemic care of people with early diabetes, IGT &/or IFG … using once daily basal insulin glargine to target a FPG < 95 mg/dl (5.3 mmol/l) for a median of 6.2 years ...
• Maintains near-normal glycemic control
• Has a neutral effect on CV outcomes & on cancers
• Slows progression of dysglycemia
• Modestly increases hypoglycemia
• Modestly increases weight
Congrés ADA 2012 Highlights
http://www.diabetes.conference-companion.com
Congrés ADA 2012 Highlights
Congrés ADA 2012 Highlights
Abstrats deadline 3 Setembre www.pcdeurope.org http://pcdeurope2012.semfyccongresos.com/registration