Actualización en diabetes

Jorge Navarro

Pubmed: artículos DM2 en 2016

• Total: 9505

• Ensayos clínicos: 195

• Metanálisis: 79

Ensayos Clínicos

Ray KK et al Lancet 2009;373:1765–1772.

All Cause MortalityIntensive vs Standard Glucose Lowering

Presented at the American Diabetes Association 76th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.

CI: confidence interval; HR: hazard ratio.

Recent trials of newer glucose-lowering agents have

been neutral on the primary CV outcome

7

SAVOR-TIMI53

EXAMINE

HR:1.0(95% CI: 0.89,

1.12)

HR: 0.96 (95% CI: UL≤1.16)

TECOSHR:0.98

(95% CI: 0.88,1.09)

EMPA-REGOUTCOME®

ELIXAHR:1.02

(95% CI: 0.89,1.17)

Empagliflozin

DPP-4inhibitors*Lixisenatide

CV, cardiovascular; HR, hazard ratio; DPP-4, dipeptidylpeptidase-4

2013

*Saxagliptin, alogliptin, sitagliptinAdapted from Johansen OE. World J Diabetes2015;6:1092-96

2014 2015

Primary outcome: 3-point MACE

9

HR0.86(95.02% CI 0.74,0.99)

p=0.0382*

Cumulative incidence function. MACE, Major Adverse Cardiovascular Event; HR, hazardratio.* Two-sided tests for superiority were conducted (statistical significance was indicated ifp≤0.0498)

Patients with

event/ analysed

Empagliflozin Placebo HR (95% CI) p-value

Primary outcome:

3-point MACE 490/4687 282/2333 0.86 (0.74, 0.99)* 0.0382

CV death 172/4687 137/2333 0.62 (0.49, 0.77) <0.0001

Non-fatal MI 213/4687 121/2333 0.87 (0.70, 1.09) 0.2189

Non-fatal stroke 150/4687 60/2333 1.24 (0.92, 1.67) 0.1638

Primary outcome

Cox regression analysis. 3-point MACE: Tim e to first oc currence of CV death, non-fatal MI or non-

fatal stroke.

MACE, Major Adverse Cardiovascular Event; HR, hazard ratio; CI, c onfidence interval; CV, c

ardiovascular; MI, myoc ardial infarction.

*95.02% CI

0,25 0,50

Favors

empagliflozin

1,00 2,00

Favors

placebo

Zinman B et al. N Engl J Med 2015 [Epub ahea d ofprint]. 1

0

Number needed to treat (NNT)to prevent one death acrosslandmark trialsinpatients withhigh CV risk

11

Simvastatin1

for 5.4years

High CV risk

5% diabetes, 26%hypertension

1994 2000

1. 4S investigator. Lancet 1994; 344: 1383-89, http://www.trialresultscenter.org/study2590-4S.htm;2.HOPE investigator N Engl J Med 2000;342:145-53,http://www.trialresultscenter.org/study2606-

HOPE.htm

2015

Pre-statinera

High CV risk

38% diabetes, 46%hypertension

Ramipril2

for 5years

Pre-ACEi/ARBera

<29% statin

Empagliflozinfor 3years

T2DM with high CV risk

92%hypertension

>80% ACEi/ARB

>75% statin

Number needed to treat(NNTs) to prevent one patient death across landmark trialsinpatients withhigh CV risk

12

Simvastatin1

for 5.4yearsRamipril2

for 5years

Pre-statinera

Pre-ACEi/ARBera

< 29% Statin

>80% ACEi/ARB

> 75% Statin

High CV risk

5% diabetes, 26%hypertension

High CV risk

38% diabetes, 46%hypertension

T2DM with high CV risk

92%hypertension

Empagliflozinfor 5years

1994 2000 2015

1:4S investigator. Lancet 1994; 344: 1383-89,http://www.trialresultscenter.org/study2590-4S.htm

2: HOPE investigator N Engl J Med2000;342:145-53, EBM2000;5:47 http://www.trialresultscenter.org/study2606-HOPE.htm

Progresión de enfermedad renal (EMPA-REG OUTCOME)

LEADER: Primary outcomeCV death, non-fatal myocardial infarction, or non-fatal stroke

The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, non-fatalmyocardial infarction, or non-fatal stroke. The cumulative incidences were estimated with the use of the Kaplan–Meier method, and thehazard ratios with the use of the Cox proportional-hazard regression model. The data analyses are truncated at 54 months, because lessthan 10% of the patients had an observation time beyond 54 months. CI: confidence interval; CV: cardiovascular; HR: hazard ratio.

Presented at the American Diabetes Association 76th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.

Expanded MACECV death, non-fatal MI, non-fatal stroke, coronary revascularization, or hospitalization for unstable angina pectoris or heart failure

The cumulative incidences were estimated with the use of the Kaplan–Meier method, and the hazard ratios with the use of the Cox proportional-hazard regression model. The data analyses are truncated at 54 months, because less than 10% of the patients had an observation time beyond 54 months.CI: confidence interval; CV: cardiovascular; HR: hazard ratio; MACE: major adverse cardiovascular event; MI: myocardial infarction.

Presented at the American Diabetes Association 76th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.

Hypoglycemia

Confirmed hypoglycemia was defined as plasma glucose level of less than 56 mg per deciliter (3.1 mmol per liter) or a severe event. Severe hypoglycemia was defined as hypoglycemia for which the patient required assistance from a third party. Analyzed using a negative binomial regression model.CI: confidence interval; PG: plasma glucose.

Presented at the American Diabetes Association 76th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.

Number needed to treat to prevent one…

CV: cardiovascular; MACE: major adverse cardiovascular event.

Presented at the American Diabetes Association 76th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.

Glucagon-like peptide-1 receptor agonists

CI: confidence interval; CV: cardiovascular; HR: hazard ratio; MI: myocardial infarction.Pfeffer MA et al. N Engl J Med 2015;373:2247–2257.

ELIXATime to first occurrence of CV death, non-fatal MI, non-fatal stroke or hospitalization for unstable angina

LEADERTime to first occurrence of CV death, non-fatal MI or non-fatal stroke

Presented at the American Diabetes Association 76th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.

Empagliflozin and Liraglutide

CI: confidence interval; CV: cardiovascular; HR: hazard ratio; MI: myocardial infarction.Zinman B et al. N Engl J Med 2015;373:2117-2128.

EMPA-REG OUTCOME LEADERCV death, non-fatal MI, or non-fatal stroke CV death, non-fatal MI, or non-fatal stroke

Presented at the American Diabetes Association 76th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.

Individual components of the primary endpoint

*95.02% CI.CV: cardiovascular; Empa: empaglifloin; Lira: liraglutide; MACE: major adverse cardiovascular event; MI: myocardial infarction; Pbo: placebo.Zinman B et al. Presented at European Association for the Study of Diabetes 2015, Stockholm, Sweden.

EMPA-REG OUTCOME LEADER

Presented at the American Diabetes Association 76th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.

SUSTAIN-6

Resultados

Marso SP et a. N Engl J Med. 2016 Sep 15.

Sustain-6:Complicaciones microvasculares

Metanálisis

Otros estudios

Guías de Práctica Clínica

ADA 2016

Diabetes Care. Standards of Medical Care. in Diabetes—2016January 2016 Volume 39, Supplement 1

Algoritmo de insulinización

Diabetes Care. Standards of Medical Care. in Diabetes—2016January 2016 Volume 39, Supplement 1

Garber, AJ; Abrahamson, MJ; Barzilay, JI et al. CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM – 2016 EXECUTIVE SUMMARY. Endocrine Practice 2016; 22 (1):84-113

Algoritmo

Estrategia terapéutica:

1) Inicial: monoterapia.2) Primera intensificación:

tratamiento dual no insulínico.

3) Segunda intensificación:triple tratamiento con o sin insulina.

Intensificación si HbA1c ≥ 7,5%

Algoritmo NICE 2016