Dichiarazione diConflitto di Interessi

Honorarium as a speaker in Scientific EventsSigma-Tau Lilly/Boheringer IngelheimAstraZeneca BMS Takeda JanssenEli-Lilly Sanofi-Aventis Menarini DiagMSD Novo Nordisk Roche DiagNovartis Servier Bayer

Grant supportNovo Nordisk (Investigator-Initiated-Study Grant) Kellogg (Investigator-Initiated-Study Grant)

AstraZeneca, Lilly, Sanofi, Novo Nordisk, Sigma-Tau, Menarini Diag(Travel grants)

Scientific advisory boardsAstraZeneca, Lilly, Sanofi

Il rischio CVD nel diabete di tipo 2Gli studi RCT

Gianluca PerseghinDipartimento di Medicina e Chirurgia

Università degli Studi di Milano Bicocca

Dipartimento di Medicina Interna e RiabilitazionePoliclinico di Monza, Monza

Type 2 diabetes is associated with a decrease in life expectancy from CV causes

Adapted from The Emerging Risk Factors Collaboration. N Engl J Med 2011

Year

s of

life

lost

a

WomenMen 7

6

5

4

3

2

1

00 40 50 60 70 80 90

Age (years)

6.8 yrs6.4 yrs

5.4 yrs

7

6

5

4

3

2

1

00 40 50 60 70 80 90

6.3 yrs

5.8 yrs

4.5 yrs

Year

s of

life

lost

a

A 50-year-old man with diabetes but no vascular disease has a decrease in life expectancy of ~6 years

Age (years)

Estimated future years of life lost due to diabetes

X 2

RCTs di trattamento intensivoUKPDS, ACCORD, VADT, ADVANCE

14% CVD risk reductionLimitation # 1: takes long timeLimitation # 2: hypoglycemia

RCTslife-style intervention

Dieta Mediterranea (?)

Estruch R et al N Engl J Med 2013

End point: eventi cardiovascolari

Mortalità CV nel diabete di tipo 2con intervento sullo stile di vita (?)

Look Ahead NEJM , 2013

RCTsdrugs

Years of Follow-up

Prop

ortio

n wi

th 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

ORIGIN

Origin trialists N Engl J Med 2012

Holman RR et al LancetDiabetes Endocrinol, 2017

Previous CVD: 10-12%

TOSCA.IT

Vaccaro O et al LancetDiabetes Endocrinol, 2017

ProactivePioglitazone

IRISPioglitazone

Kernan WN et al N Engl J Med, 2016

La meta-analisi diSteven Nissen

Conseguenza della meta-analisi diSteven Nissen

DPP4-i CVOT studies

1.02 (0.89-1.17)2.1

Presented at the 77th Scientific Sessions of the American Diabetes Association; June 12, 2017; San Diego, CA.

19

• In the DECLARE (Dapagliflozin Effect on Cardiovascular Events)-TIMI 58 trial, Dapagliflozin achieved a statistically-significant reduction in the composite endpoint of hospitalization for heart failure (hHF) or CV death, one of the two primary efficacy endpoints

• A full evaluation of the DECLARE-TIMI 58 data is ongoing, and detailed study results will be presented on the 10th of November at the American Heart Association Scientific Session 2018 in Chicago, USA.

Declare TIMI

Wittbrodt ET et alAm J Manag Care 2018

All-cause HR 0.94 HR 0.85 HR 1.05 HR: 0.86 HR: 0.95 Mortality CI95%: 0.78-1.13 CI95%: 0.74-0.97 CI95%: 0.74-1.50 CI95%: 0.77-0.97 CI95% 0.79-1.16

P=0.50 P=0.02 P=0.79 P=0.016 P=0.644

AlbiglutideHARMONY

HR: 0.78CI95% (0.68-0.90)P=0.0006

HR: 0.93CI95% (0.73-1.19)P=0.578 HR: 0.75CI95% (0.61-0.90)P=0.003HR: 0.86CI95% (0.66-1.14)P=0.300

GLP1-RA CVOT studies

Wittbrodt ET et alAm J Manag Care 2018

Quale ricaduta nellapratica clinica quotidiana ?

Conclusioni 1

Davies MJ et al Diabetes Care, 2018

Conclusioni 2

«Task» del diabetologo

Gaede P et al, N Engl J Med, 2008