Gianluca Perseghin

Investigator’s Meeting DARWIN‐T2D“Clinical characteristics of type 2 diabetic patients at the

time they start Dapagliflozin in the real world.A retrospective multicenter descriptive study”

Efficacia e sicurezzadegli SGLT2 - in

Disclosure of the CoIHonorarium as a speaker in Scientific EventsSigma-Tau Lilly/Boheringer IngelheimAstraZeneca BMS Takeda AbbottEli-Lilly Sanofi-Aventis Menarini DiagMerck & Co/Schering Plough 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 (Travel grants)

Scientific advisory boardsAstraZeneca, Lilly, Sanofi

Meccanismo d’azione

SGLT, sodium glucose cotransporter.*Loss of ~ 80 g of glucose per day = 240 cal/day

Urinary glucose excretion via SGLT2 inhibition

SGLT2SGLT2inhibitor

SGLT1

SGLT2 inhibitors reduce glucose re-absorption

in the proximal tubule, leading to

urinary glucose excretion* and

osmotic diuresis

Filtered glucose load > 180

g/day

Bakris GL et al. Kidney Int 2009

De Fronzo RA et al Diabetes Care, 2013

Filtrazione, riassorbimentoed escrezione del glucosio

effetto dell’inibizione di SGLT2

Glucose mmol/L

Rat

e (m

g/m

in)

Merovci A et al J Clin Invest 2014

Acute SGLT2 inhibition, EGP and glucagon

Ferrannini E et al J Clin Invest 2014

Meccanismo d’azione

Increase in Glucose Excretion Observed Over 2 Years

Efficacia terapeuticaEnd-points glicemici

Gliflozina: efficacia terapeutica ?

Bailey CJ et al Lancet 2010

Andamento HbA1c nel tempo

SGLT2-in: effetto sul peso corporeo

Bailey CJ et al Lancet 2010

Massa corporea

Canagliflozin add-on a metforminavs. Sitagliptin

LS meanchange

0%(95% Cl: –0.12, 0.12)–0.73%

–0.73%

–0.88%–0.15%

(95% Cl: –0.27, –0.03)

• CANA 100 and CANA 300 mg demonstrated non-inferiority to SITA 100 mg in HbA1c-lowering;

• CANA 300 mg showed statistical superiority to SITA 100 mg in HbA1c-lowering

Lavalle-González FJ et al. Diabetologia 2013

Change in HbA1c

Sita 100Cana 100

Cana 300

Canagliflozin (add-on metformin)

Cefalu WT et al. Lancet 2013; Jul 11

Mea

n Hb

A 1c

chan

ge (%

)M

ean

HbA 1

c(%

)

Patie

nts w

ith

hypo

glyc

emia

(%)

Patie

nts o

n ta

rget

fo

r HbA

1c(%

)

Effect of SGLT2-in add-on to basal insulin

SGLT2-in: efficacia terapeutica durevole ?

Andamento HbA1c nel tempo

Bailey CJ et al BMC Medicine 2013

Non induce ipoglicemia

Non induce ipoglicemia

Bailey CJ et al Lancet 2010

Ipoglicemia severa

Rosenstock J et al Diabetes Care 2012

Previene le complicanze microvascolaridel diabete

Empa-Reg Renal

Wanner C et al N Engl J Med, 2016

Progression to macroalbuminuriadoubling of the serum creatinine levelinitiation of renal-replacement therapydeath from renal disease

Wanner C et al N Engl J Med, 2016

Change in eGFR during trial

Summary of the renal end points

Wanner C et al N Engl J Med, 2016

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

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

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

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Prevenga le complicanzeCVD diabete

Empa-REG: Primary outcome3-point MACE

Zinman B et al N Engl J Med, 2015

Empa-REG: Secondary Outcomes

Zinman B et al N Engl J Med, 2015

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

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

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…… con buon profilo di sicurezza

?

Il paziente anzianoEmpareg

Canvas e Canvas R

Il paziente con IRCEmpareg

Canvas e Canvas R

Le IVU

Le infezioni genitaliEmpareg

Canvas e Canvas R

Canvas e Canvas R

Empareg

La DKA euglicemica

Le fratture

Empareg

Empareg

Canvas

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

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

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

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

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

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

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

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

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

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

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

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

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GFR during euglycemia and hyerglycemiain patients with type 1 diabetes

Cherney DZI et al Circulation 2014

Treatment period8 weeks