title: Hypoglycemia hospitalization frequency in patients with type 2 diabetes mellitus: a comparison of dipeptidyl peptidase 4 inhibitors and insulin secretagogues using the French health insurance database.
abstract: OBJECTIVE
  We aimed to compare the frequency of severe hypoglycemia leading to hospitalization (HH) and emergency visits (EV) for any cause in patients with type 2 diabetes mellitus exposed to dipeptidyl peptidase 4 (DPP4) inhibitors (DPP4-i) versus those exposed to insulin secretagogues (IS; sulfonylureas or glinides).
  
  
  METHODS
  Data were extracted from the EGB (Echantillon Généraliste des Bénéficiaires) database, comprising a representative sample of ~1% of patients registered in the French National Health Insurance System (~600,000 patients). Type 2 diabetes mellitus patients exposed to regimens containing either a DPP4-i (excluding treatment with IS, insulin, or glucagon-like peptide 1 analog) or IS (excluding treatment with insulin and any incretin therapy) between 2009 and 2012 were selected. HH and EV during the exposure periods were identified in both cohorts. A similar analysis was conducted considering vildagliptin alone versus IS. Comparative analyses adjusting for covariates within the model (subjects matched for key characteristics) and using multinomial regression models were performed.
  
  
  RESULTS
  Overall, 7,152 patients exposed to any DPP4-i and 1,440 patients exposed to vildagliptin were compared to 10,019 patients exposed to IS. Eight patients (0.11%) from the DPP4-i cohort and none from the vildagliptin cohort (0.0%) were hospitalized for hypoglycemia versus 130 patients (1.30%) from the IS cohort (138 hospitalizations) (P=0.02 and P<0.0001, respectively). Crude rates of HH/1,000 patient-years were 1.4 (95% CI: 0.7; 2.4) in the DPP4-i cohort, 0.0 in the vildagliptin cohort (95% CI: 0.0; 4.0), versus 5.6 (95% CI, 4.7; 6.6) in the IS cohort (P<0.0001). After adjustments, rates per 1,000 patient-years of HH were 1.4 (95% CI: 0.7; 2.4) with DPP4-i versus 7.5 (95% CI: 6.0; 9.2) with IS (P<0.0001), and 0.0 (95% CI: 0.0; 4.0) with vildagliptin versus 13.6 (95% CI: 10.4; 17.5) with IS (P<0.0001). Adjusted EV rates were also significantly lower with all DPP4-i or with vildagliptin, as compared to IS (P<0.0001). Consistent results were found when considering only treatment initiations for all compared cohorts.
  
  
  CONCLUSIONS
  HH and EV were significantly less frequent in patients exposed to any DPP4-i or to vildagliptin versus IS. These real-life data should be considered in the benefit/risk evaluation of the drugs.
authors.affiliation: Cemka-Eval, Bourg-la Reine, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Detournay
authors.affiliation: Department of Diabetology, Endocrinology and Nutrition, Grenoble University Hospital Center, Grenoble, France ; University Joseph Fourier, Grenoble, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Halimi
authors.affiliation: Cemka-Eval, Bourg-la Reine, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Robert
authors.affiliation: Novartis Pharma SAS, Market Access Department, Rueil-Malmaison, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Deschaseaux
authors.affiliation: Novartis Pharma SAS, Medical and Scientific Affairs, Rueil Malmaison, France ; Department of Diabetology, Metabolism and Endocrinology, Pitié-Salpétrière Hospital, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Dejager
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004636:Emergency Service, Hospital / Q000706:statistics & numerical data*; D005260:Female; D005602:France / Q000453:epidemiology; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007003:Hypoglycemia / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology*; D007348:Insurance, Health; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000627:therapeutic use*; D012044:Regression Analysis; D013453:Sulfonylurea Compounds; D000077597:Vildagliptin
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D009570:Nitriles; D011759:Pyrrolidines; D013453:Sulfonylurea Compounds; D000077597:Vildagliptin; D000218:Adamantane
keywords: DPP4 inhibitors; hospitalization; severe hypoglycemia; sulfonylureas; type 2 diabetes; vildagliptin