Le plus sûr, c'est de n'être sûr de rien. Voltaire

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1 Le plus sûr, c'est de n'être sûr de rien Voltaire

2 Analyse des faits Quatre articles publiés en juillet dans Diabetologia: Hemkenset al.: Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study (Germany) JonassonJM et al: Insulin glargineuse and short-term incidence of malignancies a population-based follow-up study in Sweden BrearleyS et al. for SDRN Epidemiology Group: Use of insulin glargineand cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group Currie CJ et al: The influence of glucose-lowering therapies on cancer risk in type 2 diabetes (UK)

3 La dose quotidienne (totale) d insuline est plus élevée dans le groupe insulines humaines que dans celui de la glargine (médiane: 37 vs 22U )

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5 FACTS Cancer risk (in general and breast) in three cohorts * (1) glargine (monotherapy) (2) glargine combined to other insulins (3) no glargine in the insulin scheme [ * n = ] Jonasson et al, 2009

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7 (p=0.004)

8 Analyse des faits Currieet al, UK Bénéfice statistique de la metformine du risque de cancer (en général) si administration avec des sulfamides ou de l insuline Insulinothérapie du risque de cancers du colon et du pancréas (pas du sein ni prostate) Absence d «effet cancer»des analogues par rapport aux insulines conventionnelles

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10 Kurtzhals et al, 2000

11 Analyses contradictoires: aucune association glargine/cancers Rosenstock et al, 2009 glargine vs NPH (n=1017) Home et Lagarenne, 2009 glargine vs NPH (20/31 études; n=10880) Dejgaard et al, 2009 (n=9000) detemir vs NPH/glargine

12 Rosenstock et al, 2009

13 In these randomised controlled diabetes trials, patients treated with insulin detemir had a lower or similar occurrence of a cancer diagnosis compared with patients treated with NPH insulin or insulin glargine,respectively

14 Insulines et cancers : Données récentes (et contradictoires) To kill an error is as good a service, and sometimes even better than the establishing of a new truth or fact Charles Darwin

15 Inoue et al, 2006

16 Rapp et al, Diabetologia 2006

17 Cancers dans le diabète de type 2 Hépatocarcinome Inoue et al El Serag et al x2 x2 Cancer du pancréas Li et al x2 Jamal et al x2 Cancer colorectal Larsson et al 26% Yang et al 42% Cancer des voies biliaires Jamal et al x2 Seins Larsson et al 20%

18 Cancers dans le diabète de type 2 Prostate Gong et al 47% (28%) Bonovas et al 10% Kasper et al 16%

19 D.Simon, 2009

20 Calle et al,new Engl J Med, 2003

21 D.Simon, 2009

22 Voies de signalisation de l insuline Vigneri et al,2009

23 Voies de signalisation Vigneri,2009

24 Diabète de type 2 et cancers : hypothèse étiopathogénique

25 Yang, Gastroenterology, 2009

26 Yang et al, Gastroenterology, 2004

27 Diabète de type 2 analogues [glargine] Insulinorésistance insulines [insulinostimulants] (?) Hyperinsulinémie Récepteurs Récepteurs IGF-1 insuline Prolifération

28 Conclusions Il existe une augmentation des cancers en cas de diabète de type 2. L'hyperinsulinémie pourrait être le lien étiopathogénique. Les résultats des études "glargine" ne sont pas concordants mais constituent un signal incitant à d'autres enquêtes. A ce stade néanmoins, aucune modification de traitement n a été, logiquement, recommandée.

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31 DARTS Pilot Observationnel Study Case-control study of subjects (UK) including newly- diagnosed Type 2 Diabetes patients. 923 were admitted with malignant cancer ( ) Patients were stratified whether they received Metformin or not Receipt of Metformin was associated with a reduce risk of cancer with a greater protective effect with increasing duration of exposure and the total doses dispensed. Adjusted* OR for any exposure to metformine = 0.77 ( ) 0.92) Evans JMM et al. BMJ 2005; 330: *adjusted for BMI,BP, smoking

32 Role of Diabetes Treatment in Cancer Saskatchewan Health database Population-based cohort study ~ 1,000,000 subjects The cohort contained diabetic patients, of whom 6969 received Metformin, and 3340 a Sulfonylurea Compared cancer-related related mortality according to use OAD or insulin Cancer mortality over 5.4±1.9 yrs of follow-up : 4.9% in sulfonylurea monotherapy users 3.5% in metformin users (3.3%( in monotherapy) 5.8% in insulin users (vs. 3.6% without insulin) HR for cancer death: SU vs. Metformine =1.3 ( ) 1.6) Insulin vs. no insulin = 1.9 ( ) Bowker SL et al. Diabetes Care 2006; 29: 254-8

33 Cancer events in ADOPT and RECORD studies (metformine,rosiglitazone and sulfonylureas) Home et al, Diabetologia,2010

34 Conclusions 1. There is a modest increase in cases of malignancies in the presence of diabetes. 2. Hyperinsulinemia could be the link. 3. Concerns about a relationship between glargine and cancer are insufficient to bring in a verdict and were not confirmed by recent papers. These observations, however, require further analyses and evaluation. 4. Up to now, scientific organizations (ADA, EASD, SFD) advised patients to maintain their insulin treatment unchanged. 5. Metformine could have anticancer effects, which have to be confirmed.