Nuevos datos de impacto€¦ · Asociación entre sulfonilureas y mortalidad cardiovascular frente...

Nuevos datos de impacto

publicados sobre los fármacos

para diabetes en el último año.

Dr. Luís Ávila

Dr. Joan Barrot

III Jornadas GdT Diabetes de la semFYC

Ea… Bah…

Dr. Luís Ávila Dr. Joan Barrot

Generalidades ADNIs


Potencia de descenso de HB a1c de los ADNIs

JAMA. 2016;316(3):313-324. doi:10.1001/jama.2016.9400

Avogaro A, Fadini GP, Sesti G, Bonora E, Del Prato S. Continued efforts to translate diabetes cardiovascular outcome trials into clinical practice. Cardiovasc Diabetol [Internet]. 11 de agosto de 2016 [citado 12 de octubre de 2016];15. Disponible en: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982334/

Evidencia de los antidiabéticos en la insuficiencia renal

Fármacos :

• Metformina

• SU

• Glitazonas

• IDPP4

• inh SGLT-2

• Análogos GLP-1

• Insulinas


Metformina :


BMJ 2016;352:h6748 doi: 10.1136/bmj.h6748

• Risk of bias in UKPDS

• Is UKPDS 10 year follow-up report reliable?

Metformina :

• Tratamiento “primera” linea DM2.

• Tratamiento pre-Diabetes, prevenir o retrasar la progresión a DM

• Efectivo en el tratamiento de la Diabetes Gestacional

• Efectivo en el tratamiento de SOPQ

• Uso en “síndrome metabólico”

• Beneficios CV (PA , lípidos , endotelio, peso, fibrinogeno..)

• efecto antioncogénico?

• efecto anti-edad?

• FDA /EMA, indicación en FG


Sulfonilureas


Hippisley-Cox J, Coupland C. Diabetes treatments and risk of heart failure, cardiovascular disease, and all cause

mortality: cohort study in primary care. BMJ. 13 de julio de 2016;354:i3477.

http://www.bmj.com/content/354/bmj.i3477.long

http://www.bmj.com/content/354/bmj.i3477.long

Rados DV, Pinto LC, Remonti LR, Leitão CB, Gross JL (2016) The Association between Sulfonylurea Use and All-Cause and

Cardiovascular Mortality: A Meta-Analysis with Trial Sequential Analysis of Randomized Clinical Trials. PLoS Med 13(4): e1001992.

doi:10.1371/journal.pmed.1001992

http://journals.plos.org/plosmedicine/article?id=info:doi/10.1371/journal.pmed.1001992

Asociación entre sulfonilureas y mortalidad cardiovascular frente aa placebo

Sulfonylureas are not associated with increased risk

for all-cause mortality, cardiovascular mortality,

myocardial infarction, or stroke. Current evidence

supports the safety of sulfonylureas; an absolute

risk of 0.5% could be firmly discarded.

Sulfonilureas

de segunda y

tercera

generación

http://journals.plos.org/plosmedicine/article?id=info:doi/10.1371/journal.pmed.1001992

Pladevall M, Riera-Guardia N, Margulis AV, Varas-Lorenzo C, Calingaert B, Perez-

Gutthann S. Cardiovascular risk associated with the use of glitazones, metformin and

sufonylureas: meta-analysis of published observational studies. BMC Cardiovascular

Disorders. 2016;16:14.

http://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-016-0187-5

• Metformin and rosiglitazone versus

sulfonylureas I 2 ≥ 70 %

• Sulfonylurea versus metformin I 2 = 41 %

• Pioglitazone versus metformin I 2 = 17 %

http://bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-016-0187-5

Glitazonas


Pioglitazone use and risk of bladder cancer: population based cohort study

- bmj.i1541.full.pdf [Internet]. [citado 25 de octubre de 2016]. Disponible

en: http://www.bmj.com/content/bmj/352/bmj.i1541.full.pdf

La pioglitazona

se relaciona

con el cancer de

vejiga

Korhonen P, Heintjes EM, Williams R, Hoti F, Christopher S, Majak M, et al. Pioglitazone use

and risk of bladder cancer in patients with type 2 diabetes: retrospective cohort study using

datasets from four European countries. BMJ. 16 de agosto de 2016;354:i3903.

http://www.bmj.com/content/bmj/354/bmj.i3903.full.pdf

La pioglitazona NO se relaciona

con el cancer de vejiga

http://www.bmj.com/content/bmj/354/bmj.i3903.full.pdf

IDPP4 :

• Insuficiencia cardíaca

• Fracturas

• Pancreatitis



Lancet Diabetes Endocrinol . January 22,2016

• IDPP4

• Long-acting DPP4i (omarigliptin) • similar efficacy and tolerability as Sita (phase 3)

• iSGLT2

• Severals further SGLT2 • similar efficacy in CT

• Sotagliflozin (inhibits both SGLT2 and 1)

• iSGLT1 (phase 1)

Diabetes care 2001;24:1614-1619

Am Heart J. 2011;162:938-48

Parry. Circ Heart Fail.2015.

Heart failure in Type 2 diabetes

DM ↑ prevalencia de IC 10-22% , 4v. más vs. no DM

Incidencia aumenta con la edad.

Riesgo IC en DM2 , relación HbA1c

A1c < 6% , HR 1.60 (1.38-1.86)

A1c > 10%, HR 1.80 (1.60-2.16)


SAVOR-TIMI 53, EXAMINE AND TECOS:

Hospitalization for heart Failure Meta-analysis.

N Eng J Med 2013;369:1317-1326

N Eng J Med 2013;369:1327-1335

N Eng J Med 2013;373:232–242

Study Drug

n/N(%)

Placebo

n/N(%)RR IC 95% p value

SAVOR-TIMI

(Saxa vs. placebo)

289/8280

3.5%

228/8212

2.8%1.27 1.07-1.51 0.09

EXAMINE

(Alo vs. placebo)

106/1701

3.9%

89/2679

3.3%1.19 0.89-1.58 0.23

TECOS

(Sita vs. placebo)

228/7332

3.1%

229/7339

3.1%1.00 0.81-1.19 0.98

SAVOR+EXAMINE+

TECOS

623/18313

3.4%

546/18230

3.0%1.14 0.97-1.34

0 21Favors

Treatment

Favors

placebo

ADVANCE 4.8%

ACCORD 2%

VADT/ORIGIN/UKPDS/DCCT - HF EXCLUDED


• Cohorts 1,499,650 ; 29,741 hospitalized for HF (9.2 events per 1000 persons per year).


N Engl J Med 2016;374:1145-54

with HF no HF

No history of HF (0.82; 0.67-1.00). With HF (0.86; 0.62-1.19)

• n 196.986 T2DM previous HF (2009 and 2013).

• n 30.204 DPP-4i and 166.782 non-users.

• outcomes: all-cause mortality, combination MI and ischaemic stroke, and hospitalisation for HF.


Ou S-M, et al. Heart 2016;0:1–7.

BMJ 2016;352:i610

43 trials (n=68 775) and 12 observational studies (n=1 777 358).

38 trials reported HF (n 21.680 ) , 87% trials reported FH as serious AE

Risk of HF iDPP4 vs control 0.97 ( 0.61-1.56)

Risk of hospital admission for HF 1.13 ( 1.00-1.26) 5 trials

Risk of hospital admission for HF 1.41 ( 0.95-2.09) 12 observational studies

vilda

Lina


Association Between Hospitalization for Heart Failure

and DPP4i in T2DM

Diab Care 2016.DOI: 10.2337/dc15-0764

With baseline CVD No baseline CVD

IPDD4 vs. SU RR 0.95 ( 0.78-1.15) p 0.580 RR 0.59 ( 0.38-0.89) p 0.013

SAVOR ( Saxa) heart failure HR, 1.27(1.07- 1.51)

TECOS ( Sita ) heart failure HR, 1.00 (0.83- 1.20)

EXAMINE ( Alo) heart failure HR, 1.19 (0.89 -1.50)

CAROLINA (Lina) ……} IDPP4 vs. SU

Saxa vs. Sita


• T2DM and osteoporosis are both common and chronic conditions that increase with age

• Insulin or SU or thiazolidinediones , might further increase the risk of osteoporotic fracture .


J Clin Endocrinol Metab. 2016 Mar 1:jc20154180.

n 8.894 Sita, n 63.834 no Sita , 181.139 per/any de seguiment

Agent RR (95% CI) p-value

Stagliptin

Metformin

SU

ThiazolidineIns

Insulin

1.1 (0.8-1.4)

1.0 (0.8-1.2)

1.3 (1.1-1.5)

1.2 (1.04-1.5)

2.1 (1.04-2.8)

0.7

1.0

0.008

0.019

<0.001

SAVOR-TIMI 53, EXAMINE AND TECOS:Meta-analysis of Pancreatitis.

Unpublished. ADA 2015

RR IC 95% p value

SAVOR-TIMI

(Saxa vs. placebo)1.375 0.721- 2.619 0.09

EXAMINE

(Alo vs. placebo)1.490 0.608 - 3.651 0.23

TECOS

(Sita vs. placebo) 1.921 0.955 - 3.864 0.98

SAVOR+EXAMINE+TECOS 1.578 1.038 - 2.399

0,1 101Favors

Treatment

Favors

placebo

11ª Jornada de l’Associació Catalana de Diabetes

Cardiovascular and non-cardiovascular safety of DPP4i: a meta-analysis of randomized controlled CV outcome trials

Diab Obe Meta, 2016 ;18: 295–299.

SAVOR , EXAMINE and TECOS trials, 3334 CV events

RR CV death+IAM nonfatal+AVC nonfatal 0.99 (0.93-1.06)

RR CV death 1.01 (0.91-1.12)

RR nonfatal IAM 0.98 (0.89-1.09)

RR nonfatal AVC 1.00 (0.86-1.16)

RR Hospital for HF 1.12 (1.00-1.25)

RR Acute pancreatitis 1.79 (1.13-2.81)

RR Pancreatitis cancer 0.55 (0.29-1.03)

RR Serious hypoglycaemia 1.14 (0.95-1.38)

RR Any hypoglycaemia 1.12 (1.05-1.20)

Gastroenterology 2011;141:150-6 ++

N Engl J Med 2013;369:1317-1326, SAVOR

N Engl J Med 2013;369:1327-1335, EXAMINE

5.5 extra cases /10.000 patients /years


iSGLT2 :

• Fracturas

• Renal & albuminuria

• Eventos CV


Scheen .Nat Rev Cardiol 2013;10:73

Efectos pleotróficos ➞ protección CV ?

iDPP4 iSGLT2

Inzucchi. Diab Vasc Dis Res 2015;12:90-100


Scheen .Nat Rev Cardiol 2013;10:73

Efectos pleotróficos ➞ protección CV ?

iDPP4 iSGLT2

Inzucchi. Diab Vasc Dis Res 2015;12:90-100


• No hipoglucemia.

• Pancreatitits?

• C. Pancreas ?

• IC ( Saxagliptina)

• Indicación en ERC ( modificar dosis , excepto Lina )

• No hipoglucemia.

• Infección genital, hongos

• ITU

• Hipotensión / deshidratación

• Cetoacidosis euglicemica

• Fracturas (canagliflozina)

• Amptuación dedos ( canagliflozina)

• Restricción en ERC

Scheen .Expert Opinion on Drug Metab & Toxicol. 2016

DPP-4 inh. plus SGLT-2 inh. as combination therapy for T2DM:

from rationale to clinical aspects


• IDPP-4 No inferioridad

• Sitagliptina Tecos

• Alogliptina Examine

• Saxagliptina Savor

timi-53

• Linagliptina Carolina

• Vildagliptina

Estudios de seguridad cardiovascular

• GLP-1

• Liraglutida Leader

• Dulaglutida Award

• Exenatida Duration

• Lixisenatida Elixa

• Semaglutide Sustain

Leader cardiovascularLEADER results announced at #2016ADA – compared to placebo, Victoza reduces risk of cardiovascular death by 22%, plus a 22% reduction in kidney disease and 31% reduction in

severe hypoglycemia.

Reduccion de mortalidad

cardiovascular

22 %

Reduccion hipogluclemias

severas

31 %

Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JFE, Nauck MA, et al. Liraglutide

and Cardiovascular Outcomes in Type 2 Diabetes. New England Journal of Medicine. 28 de julio

de 2016;375(4):311-22.

http://www.nejm.org/doi/full/10.1056/NEJMoa1603827#t=article

RCT


Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JFE, Nauck MA, et al.

Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. New England Journal of

Medicine. 28 de julio de 2016;375(4):311-22.


RCT

Mas eficaz en:

Mas jóvenes

Mas obesos

Con menor duración de la diabetes

Paciente en prevención secundaria

Sin insuficienca cardiaca

Con filtrado glomerulares entre 60 y 30

Sin diferencia de sexos

Leader cardiovascular


Efecto de los fármacos incretínicos sobre la ICC

Filion KB, Azoulay L, Platt RW, Dahl M, Dormuth CR, Clemens KK, et al. A Multicenter Observational Study of Incretin-based Drugs and Heart Failure. New England Journal of Medicine. 24 de marzo de

2016;374(12):1145-54.

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1506115

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1506115

Figure 2. Changes from baseline in metabolic parameters and liver enzymes according to treatment groupMean change from

baseline during treatment with liraglutide or placebo for up to 48 weeks followed by a 12 week post-treatment period are shown

(dashed line) ...

Matthew James Armstrong, Piers Gaunt, Guruprasad P Aithal, Darren Barton, Diana Hull, Richard Parker, Jonathan M

Hazlehurst, Kathy Guo, George Abouda, Mark A Aldersley, Deborah Stocken, Stephen C Gough, Jeremy W Tomlinson, Rachel

M Brown, Stefan G Hübscher, Philip N Newsome

Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind,

randomised, placebo-controlled phase 2 study

null, Volume 387, Issue 10019, 2016, 679–690 http://dx.doi.org/10.1016/S0140-6736(15)00803-X

Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. New England Journal of Medicine. 15 de septiembre de 2016;0(0):null

http://www.nejm.org/doi/full/10.1056/NEJMoa1607141#t=article.

Seguridad cardiovascular de semaglutide

RRR 25%

Tamaño experimental 1648

Tamaño control 1649

Nº eventos en gr. experimental 108

Nº eventos en gr. control 146

Reducción riesgo absoluto 0.023 (2.3%)

Reducción riesgo absoluto 0.25 (25%)

OR 1.35

NNT semaglutide

Datos extraidos de : Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. New England Journal of Medicine. 15 de septiembre de 2016;0(0):null


Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. New England Journal of Medicine. 15 de septiembre de 2016;0(0):null


↓ 1.4% Hb A1c

↓ 4.9 Kg peso

www.thelancet.com/diabetes-endocrinology

PublishedonlineSeptember16,2016

http://dx.doi.org/10.1016/S2213-8587(16)30267-4

RCT

Duration-8 dapagliflozina y exenatide vs combinación

Los pacientes controlan mejor la Hb A1c

y pierden mas peso con la combinación

dapagliflozina/exenatide semanal ( -2% y

-3,41 Kg) que solo con dapagliflozina

(1,4% y 2,19 Kg) o exenatide (1,6% y

1,54 Kg)

http://www.thelancet.com/diabetes-endocrinology

http://dx.doi.org/10.1016/S2213-8587(16)30267-4

SGLT2-inhibitors : metabolic effects

• Han demostrado ↓ HbA1c, peso, PA y albuminuria. Lípidos (↑Ldl-col)

• Empagliflozina ha demostrado ↓ eventos CV y sugiere beneficios

renoprotectores

• Enlentecen la progresión de la enfermedad renal diabética

independiente del efecto glucémico.

• Dapa ha demostrado en FG 30-59 mL/min; ↓ HbA1c menor , pero la

↓ Peso y PA se mantienen.



Dalama. Rev Esp Cardiol. 2016

• DM2 (HbA1c 7.0–10.5%) + HTA mal controlada (IECA o ARA II)

• PAS 140–165 i PAD 85–105 mm Hg; CAC ≥30mg/g .


Diab Obes and Metabol 2016; 18: 590–597.

• DM2 (HbA1c 7.0–10.5%) + HTA mal controlada (IECA o ARA II)

• PAS 140–165 i PAD 85–105mm Hg); CAC ≥30mg/g .


Diab Obes and Metabol 2016; 18: 590–597.

Dapa ↓ −33.2%albuminuria [−45.4, −18.2].

Dapa ↓ FG −23.5% (−37.6, −6.3). Efecto que revierte al dejar el tratamiento.

No EA renales en ambos grupos.

Heerspink. J Am Soc Nephrol 2016.

Canagliflozin slows the progression of eGFR decline

in patients T2DM compared with glimepiride.

n 1.450 DM2 ;

Cana 100 mg, 300 mg, Glimepiride 6-8 mg

end point : canvi FG i ratio CAC als 2 anys.

Similar reducción HbA1c

Canvi FGe :

3.3 mL/min (2.8-3.8) SU

0.5 ml/min i 0.9 mL/min en Cana

CAC ≥ 30 :

Cana 100 mg - 31.7%, -49,3% vs.SU



Wu. Lancet Diab Endoc 2016. http://dx.doi.org/10.1016/

Six regulatory submissions (37 525 participants) and 57 published trials (33 385 participants)

• SGLT2 inhibitors protected against:

Risk of major adverse CV events (MACE)

CV death, heart failure, death from any cause, non-fatal MI or angina; non-fatal stroke

Safety analyses

http://dx.doi.org/10.1016/


Effects of sodium-glucose cotransporter-2 inhibitors on CV events, death, and major

safety outcomes in adults with T2DM: a systematic review and meta-analysis

Wu. Lancet Diab Endoc 2016. http://dx.doi.org/10.1016/

http://dx.doi.org/10.1016/

Effect of EMPA on bone fractures in patients with T2DM

Los DM tienen mayor riesgo de fracturas vs. no DM

• End points:fracturas (AE), marcadores óseos (FA, proteinas totales, albumina, PTH, 25-OH-Vit. D

,calcio y fosfato. Relación sexo,edad ,FG,densidad ósea (DXA)


Effect of EMPA on bone fractures in patients with T2DM

15 AC Phase I-III (con EMPA-REG) > 12.000 DM2

• % de fracturas comparables Empa vs. placebo (edad, género y FGe

• % de fracturas aumenta con la edad ( ↑mujeres y IR moderada).

EMPA-REG H2H-SU

• Empa no incrementa riesgo de fracturas vs. glimepiride 1-4 mg.

• Densidad ósea (fémur y col. lumbar) normal.


Insulinas :

• Nuevas insulinas

• Inhalada

• Consensos


Figure 2

The Lancet Diabetes & Endocrinology 2015 3, 638-652DOI: (10.1016/S2213-8587(15)00097-2) Copyright © 2015 Elsevier Ltd Terms and Conditions

Evolución de las insulinas en el tiempo

http://www.elsevier.com/termsandconditions

Date of download: 10/30/2016Copyright © 2016 American Medical Association.

All rights reserved.

From: Effect of Insulin Glargine Up-titration vs Insulin Degludec/Liraglutide on Glycated Hemoglobin Levels in

Patients With Uncontrolled Type 2 DiabetesThe DUAL V Randomized Clinical Trial

JAMA. 2016;315(9):898-907. doi:10.1001/jama.2016.1252

Date of download: 10/30/2016 Copyright © 2016 American Medical Association.



Patients With Uncontrolled Type 2 Diabetes The DUAL V Randomized Clinical Trial

JAMA. 2016;315(9):898-907. doi:10.1001/jama.2016.1252

Conclusions and Relevance

Among patients with uncontrolled

type 2 diabetes taking glargine

and metformin, treatment with

degludec/liraglutide compared with

up-titration of glargine resulted in

noninferior HbA1c levels, with

secondary analyses indicating

greater HbA1c level reduction after

26 weeks of treatment. Further

studies are needed to assess

longer-term efficacy and safety.

Date of download: 10/30/2016 Copyright © 2016 American Medical Association.



Patients With Uncontrolled Type 2 Diabetes The DUAL V Randomized Clinical Trial

JAMA. 2016;315(9):898-907. doi:10.1001/jama.2016.1252

Dosis:

Deglira 41 (16-50)

40% dosis máxima de

50 U

Glargina 66 (17-153

http://wa2jp9pc9c.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-

8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Effects+on+

All-

cause+Mortality+and+Cardiovascular+Outcomes+in+Patients+With+Type+2+Diabetes+by+Comparing+Insulin+With+Oral+Hypoglycemic+Agent+Therapy

%3A+A+Meta-

analysis+of+Randomized+Controlled+Trials&rft.jtitle=Clinical+Therapeutics&rft.au=Li%2C+Juan&rft.au=Tong%2C+Yuzhen&rft.au=Zhang%2C+Yuwei&rft.a

u=Tang%2C+Lizhi&rft.date=2016-02-01&rft.issn=0149-2918&rft.eissn=1879-

114X&rft.volume=38&rft.issue=2&rft.spage=372&rft.epage=386.e6&rft_id=info:doi/10.1016%2Fj.clinthera.2015.12.006&rft.externalDBID=n%2Fa&rft.externa

lDocID=10_1016_j_clinthera_2015_12_006&paramdict=en-US

Figure 6. Risk of stroke events. CVD = cardiovascular disease; M.H. = Mantel-Haenszel; OHA = oral hypoglycemic agent; UKPDS =

UK Prospective Diabetes Study.Juan Li, Yuzhen Tong, Yuwei Zhang, Lizhi Tang, Qingguo LV, Fang Zhang, Ruijie Hu, Nanwei Tong

Effects on All-cause Mortality and Cardiovascular Outcomes in Patients With Type 2 Diabetes by Comparing Insulin With

Oral Hypoglycemic Agent Therapy: A Meta-analysis of Randomized Controlled Trials

Clinical Therapeutics, Volume 38, Issue 2, 2016, 372–386.e6

http://dx.doi.org/10.1016/j.clinthera.2015.12.006

La insulinización no mejora el pronóstico de ADNis

NMA findings for Gla-300 versus other basal insulins in the BOT population: (A) change in

HbA1c (%); (B) change in body weight (kg); (C) risk of nocturnal hypoglycaemia; (D) risk of

documented symptomatic hypoglycaemia.

Nick Freemantle et al. BMJ Open 2016;6:e009421

©2016 by British Medical Journal Publishing Group

A. Change in HbA1c (%)

B. Change in body weight (kg)

Nick Freemantle et al. BMJ Open 2016;6:e009421©2016 by British Medical Journal Publishing Group

C. Risk of nocturnal hypoglycemia

D. risk of documented symptomatic

hypoglycaemia

NMA findings for Gla-300 versus other basal insulins in the BOT population: (A) change in

HbA1c (%); (B) change in body weight (kg); (C) risk of nocturnal hypoglycaemia; (D) risk of

documented symptomatic hypoglycaemia.

A: Mean plasma glucose concentrations over time during the course of the

study (INP (infusion i.v): –◇–; INI (40 U nasal): –■–).

Satya Dash et al. Diabetes 2015;64:766-774©2015 by American Diabetes Association

Insulinas nasal mas potentes

Liu L, Zhou C, Xia X, Liu Y. Self-assembled lecithin/chitosan nanoparticles for oral insulin delivery: preparation and functional evaluation. Int J Nanomedicine. 24 de febrero de 2016;11:761-9.

Reducción de glucosa con diferentes dosis de

insulina y administración oral (lecitina/citosan) o

subcutánea

60 U/kg oral 2 U/kg sc 40 U/kg L/C 60 U/k L/c

Kim ES, Plosker GL. AFREZZA® (insulin human) Inhalation Powder: A Review in Diabetes Mellitus. Drugs. 18 de septiembre de 2015;75(14):1679-86.

Afrezza insulina inhalada

SUSPENDIDA

Prevalence of prescribing of different anti-diabetic medications as add-on therapy in patients

with type 2 diabetes on sulfonylureas. *Other=Sum of prevalence of Acarbose, GLP-1 analogues,

Meglitinides and SGLT-2 inhibitors. **For detailed figures on point estimates and CIs, please

consult online supplementary appendix 6.

Manuj Sharma et al. BMJ Open 2016;6:e010210

©2016 by British Medical Journal Publishing Group

Gracias.

Dr. Luís Ávila

Dr. Joan Barrot

Nuevos datos de impacto€¦ · Asociación entre sulfonilureas y mortalidad cardiovascular frente...

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