Quelles Nouveautés s dans les Recommandations 2015?? 1. Abaissement du cut-off BMI chez les patients asiatiques pour le dépistage d

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1 Quelles Nouveautés s dans les Recommandations 2015?? 1. Abaissement du cut-off BMI chez les patients asiatiques pour le dépistage d du diabète de type 2

2 Quelles Nouveautés s dans les Recommandations 2015?? 2. Augmentation activité physique/pas d avantage d à l utilisation de la cigarette électronique/précision cision concernant la vaccination pneumocoque

3 Quelles Nouveautés s dans les Recommandations 2015?? 3. Modifications des chiffres-cibles cibles de TA ( mmhg) ) et des valeurs de la glycémie à jeun ( mg/dl)

4 Quelles Nouveautés s dans les Recommandations 2015?? 4. Quelle stratégie pour le contrôle lipidique?

5 Quelles Nouveautés s dans les Recommandations 2015?? 5. a: Valeurs-cibles enfants et adolescents 5. b: Pieds diabétiques 5. c: Diabète et grossesse

6 Les Grands Standards 2015??

7 ADA/EASD 2015 position statement Adapted from: Inzucchi SE, et al. Diabetes Care. 2015;38: PHBNL/CAN/0115/

8 Les Deux Grandes Nouveautés s en 2015 Les Inhibiteurs SGLT-2 Le Système Libre

9 Impact of Intensive Therapy for Diabetes: Summary of Major Clinical Trials Study Microvasc CVD Mortality UKPDS DCCT / EDIC* ACCORD ADVANCE VADT * In diabetes type 1 Kendall DM, Bergenstal RM. International Diabetes Center -UK Prospective 2009 Diabetes Study (UKPDS) Group. Lancet 1998;352:854. Holman RR et al. N Engl J Med. 2008;359:1577. DCCT Research Group. N Engl J Med 1993;329;977. Nathan DM et al. N Engl J Med. 2005;353:2643. Gerstein HC et al. N Engl J Med. 2008;358:2545. Patel A et al. N Engl J Med 2008;358:2560. Duckworth W et al. N Engl J Med 2009;360:129. (erratum: Moritz T. N Engl J Med 2009;361:1024)

10 Anti-Hyperglycemic Therapy: General Recommendations La metformine est le traitement de premiere ligne en dehors de ses contre-indications Diabetologia 2012;55:

11 Decline of -Cell Function in the UKPDS Illustrates Progressive Nature of Diabetes -cell function (% of normal by HOMA) 100? Time of diagnosis Pancreatic function = 50% of normal Years HOMA=homeostasis model assessment Adapted from Holman RR. Diab Res Clin Pract. 1998;40 (suppl):s21-s25; UKPDS. Diabetes. 1995;44:

12 Anti-Hyperglycemic Therapy: General Recommendations Apres la metformine, il y a peu de données pour nous guider. L association à 1 ou 2 antidiabétiques, oraux ou injectables, est raisonnable en évitant autant que possible les effets indésirables.

13 Properties of anti-hyperglycemic agents Class Mechanism Advantages Disadvantages Cost Biguanides Activates AMP-kinase Hepatic glucose production Extensive experience No hypoglycemia Weight neutral? CVD Gastrointestinal Lactic acidosis B-12 deficiency Contraindications Low SUs / Meglitinides Closes KATP channels Insulin secretion Extensive experience Microvasc. risk Hypoglycemia Weight gain Low durability? Ischemic preconditioning Low TZD PPAR- activator insulin sensitivity No hypoglycemia Durability TGs, HDL-C? CVD (pio) Weight gain Edema / heart failure Bone fractures? MI (rosi)? Bladder ca (pio) High -GIs Inhibits glucosidase Slows carbohydrate absorption No hypoglycemia Nonsystemic Post-prandial glucose? CVD events Gastrointestinal Dosing frequency Modest A1c Mod. DPP-4 inhibitors Inhibits DPP-4 Increases GLP-1, GIP No hypoglycemia Well tolerated Modest A1c? Pancreatitis Urticaria High GLP-1 receptor agonists Activates GLP-1 R Insulin, glucagon gastric emptying satiety Weight loss No hypoglycemia? Beta cell mass? CV protection GI? Pancreatitis Medullary ca Injectable High Insulin Activates insulin receptor peripheral glucose uptake Universally effective Unlimited efficacy Microvascular risk Hypoglycemia Weight gain? Mitogenicity Injectable Training requirements Stigma Variable Diabetologia (2012) 55:

14 Efficacité Compilation graphique de l effet thérapeutique de différents inhibiteurs de la DPP-4 en monothérapie comme mentionné dans le Résumé des Caractéristiques du Produit (RCP). Pour le changement moyen en HbA 1c corrigé par placebo, après 24 semaines de traitement par rapport à la valeur de base** Linagliptine 1 Saxagliptine 2 Sitagliptine 3 Vildagliptine 4 Dosage 5 mg QD 5 mg QD 100 mg QD 50 mg BID Valeur initiale 8,0% 8,0% 8,0% 8,4% HbA 1c Diminution moyenne de HbA 1c * -0,7% -0,6% -0,8% -0,7% n = Valeur p* < 0,0001 < 0,0001 < 0,0001 < 0,05 *Diminution moyenne de HbA1c versus placebo. **pas d étude comparative existante entre les différentes molécules. 1. Résumé des caractéristiques du produit Trajenta, 2. Résumé des caractéristiques du produit Onglyza, 3. Résumé des du produit Januvia, 4. Résumé des Caractéristiques du produit Galvus.

15 Difference in weight change was significant between saxagliptin vs SU as add-on to metformin 1 Adjusted mean change in body weight: baseline to Week 52 (safety analysis set) Adjusted mean change in body weight (kg) SE *p< * MET + SAXA (n=424) MET + GPZ (n=426) GPZ: glipizide; MET: metformin; SAXA: saxagliptin, 1. Göke B, et al Int J Clin Pract, November 2010, 64, 12,

16 Significantly fewer patients experience hypoglycaemia with saxagliptin vs SU as add-on to metformin 1 Proportion of patients (%) with 1 hypoglycaemic episode at week 52 (safety analysis set) 50 - Proportion of patients (%) ± CI * MET + SAXA (n=428) Severe hypoglycaemic events: 0 with saxagliptin vs 13 for glipizide *p< between groups CI: confidence interval; GPZ: glipizide; MET: metformin; SAXA: saxagliptin. 1. Göke B, et al Int J Clin Pract, November 2010, 64, 12,

17 Top Line Results 1-2 Saxagliptin/SAVOR Alogliptin/EXAMINE Primary MACE 1.00 ( ) 0.96 (UL 1.16) CV Death 1.03 ( ) 0.79 ( ) MI 0.95 ( ) 1.08 ( ) Stroke 1.11 ( ) 0.91 ( ) Total Mortality 1.11 ( ).88 ( ) Saxa/PBO - % Alo/Pbo - % Heart Failure Admissions 3.5/2.8* Reported at NS Hypoglycemia Mild 14.2/12.5* 6.7/6.5 Severe 2.1/1.7* 0.7/0.6 Pancreatitis n n Any 24/21 NR Acute 22/16 12/8 Chronic 2/6 5/4 Pancreatic Cancer 5/12 0/0 1. Scirica BM, et al. N Engl J Med /NEJMoa White WB et al. N Engl J Med 2013; 369: *p<0.05

18 Pancreatic Safety effets secondaires digestifs 10-20% augmentation fréquence cardiaque 250 Toxicology Studies No findings of overt pancreatic toxic effects Drug-induced pancreatic tumors absent Clinical safety data: 200 trials 28,000 exposed to incretin-based drug FDA and EMA agree: Causal association between incretin-based drugs and pancreatitis or pancreatic cancer are inconsistent with current data FDA and EMA have not reached a final conclusion regarding causal relationship On-going strategies include capture of safety information from CV outcome trials Cancer thyroidien : néant dans LEAD

19 Current and Future incretin-based therapies byetta victoza lyxumia bydureon Futurs GLP-1 Albiglutide : Erpezan Dulaglutide: Trulicity Semaglutide

20 HbA 1c effects across LEAD trials Monotherapy LEAD-3 1 Met combination LEAD-2 2 SU combination LEAD-1 3 Met + TZD combination LEAD-4 4 Met + SU combination LEAD-5 5 Met SU combination LEAD-6 6 Baseline HbA 1c (%) * * Liraglutide 1.2 mg * * * * Liraglutide 1.8 mg Glimepiride Exenatide * * Rosiglitazone Glargine Placebo Significant *vs. comparator; change in HbA 1c from baseline for overall population (LEAD-4,-5); add-on to diet and exercise failure (LEAD-3); or add-on to previous OAD monotherapy (LEAD-2,-1). HbA 1c, glycosylated haemoglobin; DPP-4, dipeptidyl petidase-4; MET, metformin; OAD, oral anti-diabetic drug; SU, sulphonylurea; TZD, thiazoladinedione. 1. Garber A et al. Lancet 2009;373: ; 2. Nauck M et al. Diabetes Care 2009;32;84 90; 3. Marre M et al. Diabet Med 2009;26; ; 4. Zinman B et al. Diabetes Care 2009;32: ; 5. Russell-Jones D et al. Diabetologia 2009;52: ; 6. Buse JB et al. Lancet 2009;374:39 47.

21 LEAD programme: weight reduction with liraglutide, all subjects Change in body weight (kg) Monotherapy LEAD % 43% Met combination LEAD SU combination LEAD * -0.2* Met + TZD combination LEAD-4-1.0* +0.6 Met + SU combination LEAD * -2.1* * -2.0* -2.6* * GLP Met and/or SU combination LEAD-6 glargine Liraglutide 1.2 mg Liraglutide 1.8 mgglimepiride Rosiglitazone Glargine Placeb Exenatid o e * Significant vs. comparator Marre et al. Diabetic Medicine 2009; /j x (LEAD-1); Nauck et al. Diabetes Care 2009;32;84 90 (LEAD-2); Garber et al. Lancet 2009;373: (LEAD-3); Zinman et al. Diabetologia 2008;51(Suppl. 1):S359 (A898) (LEAD-4); Russell-Jones et al. Diabetes 2008;57(Suppl. 1):A159 (LEAD- 5); Blonde et al. Can J Diabetes 2008;32 (Suppl.):A107 (LEAD-6)

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