Le ipoglicemie iatrogene: impatto sanitario ed economico

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1 Riflessioni su Innovazione e Appropriatezza nella terapia del Diabete Mellito tipo 2 Le ipoglicemie iatrogene: impatto sanitario ed economico 20 settembre 2014 Nh Villa Carpegna Roma Andrea Giaccari Patologia Endocrino-Metabolica Policlinico Gemelli - UCSC - Roma

2 ipoglicemie: agenda CVD cause frequenza ricoveri dati Italiani costi indiretti e sociali conseguenze terapeutiche considerazioni finali

3 CVD ipoglicemie: agenda

4 ACCORD: mortalità (tutte le cause) % HR 1.22 ( ) P = 0.04 Intensive therapy 5 Standard therapy Time (years) ACCORD Study Group. N Engl J Med. 2008;358:

5 Tasso di mortalita generale (%) Studio ACCORD: alta mortalità nei pazienti che manifestavano episodi di ipoglicemia severa 3,5 3,0 3,3% 2,5 2,0 1,5 1,0 1,2% 0,5 0,0 Nessun episodio di ipoglicemia severa Episodi di ipoglicemia severa The ACCORD Study Group. N Eng J Med 2008; 358:

6 Higher rate of severe hypoglycaemia with intensive glycaemic control* *Intensive glycaemic control was defined differently in these trials Hypoglycaemia requiring any assistance in glucose-lowering trials Conv, conventional therapy; gly, glibenclamide; HR, hazard ratio; ins, insulin; int, intensive therapy; std, standard therapy 1. UKPDS Group. Lancet 1998;352:837 53; 2. Patel et al; ADVANCE Collaborative Group. N Engl J Med 2008;358: ; 3. Gerstein et al; ACCORD Group. N Engl J Med 2008;358: ; 4. Duckworth et al. N Engl J Med 2009;360:129 39

7 L ipoglicemia è predittore di mortalità CV: VADT Rischio di morte Inferiore Superiore RR (IC) Ipoglicemia 4,042 (1,449-11,276)* HbA 1c 1,213 (1,038-1,417)** HDL-C 0,699 (0,536-0,910)* Età 2,090 (1,518-2,877)*** Evento precedente 3,116 (1,744-5,567)*** Rischio relativo *P=0,01; **P=0,02; ***P<0,01 Abraira C. Presentazione alla 68ª Sessione Scientifica della American Diabetes Association; 6-10 giugno 2008, San Francisco, USA

8 odds ratio metaregressione ipoglicemie Mannucci E et al: NMCD 19:604; 2009 differenza ipoglicemie

9 Link between hypoglycaemia and acute cardiovascular events in type 2 diabetes Retrospective, observational study (n=860,845) assessing association between hypoglycaemic events and acute cardiovascular events 3.1% patients had a hypoglycaemic event during the evaluation period (1 year) Patients with hypoglycaemic events had 79% higher odds of acute cardiovascular events than patients without hypoglycaemic events Johnston et al. Diabetes Care 2011;34:

10 Multiple logistic regression of acute CV events as a function of hypoglycaemic events Johnston et al. Diabetes Care 2011;34:

11 Adverse outcomes among patients with type 2 diabetes experiencing severe hypoglycaemia Zoungas. N Engl J Med 2010;363:1410 8, for the ADVANCE Collaborative Group

12 CVD cause ipoglicemie: agenda

13 What is hypoglycaemia? A state of neuroglycopenic and/or neurogenic symptoms due to low plasma glucose levels Low plasma glucose levels defined as: 70 mg/dl (3.9 mmol/l) (ADA) 1 <54.1 mg/dl (3.0 mmol/l) (EMA) 2 <72 mg/dl (4.0 mmol/l) (CDA) 3 Symptoms respond to the administration of carbohydrate 3 ADA, American Diabetes Association; CDA, Canadian Diabetes Association; EMA, European Medicines Agency 1. ADA. Diabetes Care 2005;28:1245 9; 2. EMA. CPMP/EWP/1080/ ; 3. Yale et al. Canadian J Diabetes 26:22 35

14 Hypoglycaemia is inconsistently reported and defined Reports of symptoms by patients with diabetes vary 1 Inter-individual variations in symptom thresholds The most common symptoms of hypoglycaemia are not always the first to be reported 1 Asymptomatic or unrecognised episodes can be missed, 3,4 especially those occurring at night and/or during sleep Hepburn et al. Diabetic Med 1993;10:231 7; 2. Zammitt & Frier. Diabetes Care 2005;28: ; 3. Chico et al. Diabetes Care 2003;26:1153 7; 4. Weber et al. Exp Clin Endocrinol Diabetes 2007;115:491 4; 5. DCCT Research Group. Am J Med 1991;90:450 9;

15 Fattori di rischio per ipoglicemia Età avanzata Numero medicine Digiuno Ipoalimentazione Malattie intercorrenti Malattie epatiche Attività fisica Alcool Malattie endocrine Perdita controregolazione Unawareness Mathieu Cc Int J Clin Pract 61:29, 2007

16 ipoglicemie: agenda CVD cause frequenza

17 Hypoglycaemic events occur frequently Patients with type 1 and 2 diabetes experience frequent hypoglycaemic events, a proportion of which are severe Donnelly et al. Diabetic Med 2005;22:749 55

18 Epidemiology of hypos in UK SU, sulphonylurea UK Hypoglycaemia Study Group. Diabetologia 2007;50:1140 7

19 Impaired awareness of hypoglycaemia is associated with higher rate of severe hypoglycaemia (type 1 or type 2) Incidence of severe hypoglycaemia in individuals with impaired awareness of hypoglycaemia Graveling & Frier. Diabetes Metab 2010;36(Suppl. 3):S64 74

20 ipoglicemie: agenda CVD cause frequenza ricoveri

21 eventi avversi iatrogeni (farmaci) Budnitz DS et al.: N Engl J Med 365:2002; 2011

22 eventi avversi: categorie farmaci Budnitz DS et al.: N Engl J Med 365:2002; 2011

23 ipoglicemie: categorie Budnitz DS et al.: N Engl J Med 365:2002; 2011

24 eventi avversi: tipi di farmaci Budnitz DS et al.: N Engl J Med 365:2002; 2011

25 ipoglicemie: agenda CVD cause frequenza ricoveri dati Italiani

26 10362 ospedalizzazioni 40% diagnosi principale 60% diagnosi secondaria Nicolucci A. p.c.

27 Tassi di incidenza per anno e per fasce d età Nicolucci A. p.c.

28 Distribuzione per tipo di diabete ed età Nicolucci A. p.c.

29 Distribuzione per tipologia di trattamento = = Nicolucci A. p.c.

30 ipoglicemie: agenda CVD cause frequenza ricoveri dati Italiani costi indiretti e sociali

31 costi indiretti delle ipoglicemie Brod M et al.: Value in Health 14:665; 2011

32 costi sociali delle ipoglicemie Brod M et al.: Value in Health 14:665; 2011

33 costi aggiuntivi delle ipoglicemie Brod M et al.: Value in Health 14:665; 2011

34 ipoglicemie: agenda CVD cause frequenza ricoveri dati Italiani costi indiretti e sociali conseguenze terapeutiche

35 reazioni del Paziente alle ipo Leiter LA et al.: Can J Diabetes 29:186; 2005

36 Patient fear of hypoglycaemia increases with history of hypoglycaemia HFS-II, Hypoglycaemia Fear Survey-II Vexiau et al. Diabetes Obes Metab 2008;10(Suppl. 1):16 24

37 Patient fear of hypoglycaemia increases with increased severity of hypoglycaemia HFS: Hypoglycaemia Fear Survey Marrett et al. Diabetes 2008;57(suppl. 1):A174

38 Hypoglycaemia is a barrier to effective glycaemic management High levels of concern over hypoglycaemia 60% of patients experienced a hypoglycaemic event in the past 12 months 76% of patients said that hypoglycaemia is one of the most fearful parts of having diabetes 74% of physicians would treat patients diabetes more ambitiously if there was no concern over hypoglycaemic events Peyrot et al. Diabetes Care 2010;33:240 5; Peyrot et al. Diabetes 2011;60(Suppl. 1):A225

39 L INERZIA glicata > 7% riduzione dose NICE 7,5 % aumento dose ipoglicemizzante perdita compliance inerzia / paura aumento rischio ipoglicemia

40 Frequency of hospitalization for hypoglycemia and of all emergency calls in T2DM patients exposed to vildagliptin vs insulin secretagogues: an analysis of the national French health-insurance database Results: 1440 patients were exposed to vildagliptin and to insulin secretagogues. After adjustments, rates of HH and of all emergency calls were significantly lower with vildagliptin vs insulin secretagogues

41 ipoglicemie: agenda CVD cause frequenza ricoveri dati Italiani costi indiretti e sociali conseguenze terapeutiche considerazioni finali

42 pro e contro della terapia intensiva Fidler C. et al.: J Med Economics 14:646; 2011

43 Le conseguenze dell ipoglicemia Morte 2,3 Perdita compliance Costi di ospedalizzazione 4 Coma 3 Complicazioni cardiovascolari 3 Aumentato rischio di demenza 1 Ipoglicemia Aumento ponderale dovuto a defensive eating 5 Riduzione della qualità della vita 7 Perdita di coscienza 3 Aumentato rischio di incidenti stradali 6 Aumentato rischio di crisi epilettiche 3 Inerzia terapeutica 1. Whitmer RA et al. JAMA. 2009; 301: ; 2. Bonds DE et al. Br Med J. 2010; 340: b4909; 3. Barnett AH. Curr Med Res Opin. 2010; 26: ; 4. Jönsson L et al. Value Health. 2006; 9: ; 5. Foley JE e Jordan J. Vasc Health Risk Manag. 2010; 6: ; 6. Begg IS et al. Can J Diabetes. 2003; 27: ; 7. McEwan P et al. Diabetes Obes Metab. 2010; 12: ; 8 Levy AR, et al. Health Qual Life Outcomes. 2008, 6: 73.