title: Novel oral glucose-lowering drugs are associated with lower risk of all-cause mortality, cardiovascular events and severe hypoglycaemia compared with insulin in patients with type 2 diabetes.
abstract: To investigate the association of novel oral glucose-lowering drugs (GLDs), compared with that of insulin, with risk of all-cause mortality, cardiovascular disease (CVD) and severe hypoglycaemia.
  
  
  
  During 2013 to 2014 all patients with type 2 diabetes in Sweden identified as new users of novel oral GLDs, either dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter-2 (SGLT2) inhibitors (only dapagliflozin available in Sweden during the study period), with those initiating insulin as a comparison group, in the Prescribed Drug Register were included and followed in the Patient and Cause of Death Registers. The novel GLD group and insulin group were matched 1:1 using propensity score. Cox regression models were used to estimate risks.
  
  
  
  Of 37 603 patients, 21 758 were matched 1:1 to novel GLD vs insulin groups, with median follow-up times of 1.51 years (16 304 patient-years) and 1.53 years (16 306 patient-years), respectively. Treatment with novel GLDs was associated with a 44% (hazard ratio [HR] 0.56 [95% confidence interval {CI} 0.49-0.64]), 15% (HR 0.85 [95% CI 0.73-0.99]) and 74% (0.26 [95% CI 0.12-0.57]) lower risk of all-cause mortality, CVD and hypoglycaemia, respectively, compared with insulin treatment. In separate analyses for the two novel GLDs, dapagliflozin was associated with lower risks of all-cause mortality and CVD (56% [HR 0.44, 95% CI 0.28-0.70] and 49% [HR 0.51, 95% CI 0.30-0.86], respectively), while DPP-4 inhibitor treatment was associated with lower risk of all-cause mortality (41% [HR 0.59, 95% CI 0.51-0.67]), but not with CVD (HR 0.87, 95% CI 0.75-1.01).
  
  
  
  Novel oral GLD treatment was associated with lower risk of all-cause mortality, CVD and severe hypoglycaemia compared with insulin treatment. Dapagliflozin was associated with a lower risk of both all-cause mortality and CVD, whereas DPP-4 inhibitor treatment was only associated with lower risk of all-cause mortality.
authors.affiliation: Unit for Diabetes Research, Division of Internal Medicine, Department of Clinical Science and Education, Karolinska Institute, Södersjukhuset, Stockholm, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nyström
authors.affiliation: AstraZeneca Nordic-Baltic, Södertälje, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Bodegard
authors.affiliation: Unit for Diabetes Research, Division of Internal Medicine, Department of Clinical Science and Education, Karolinska Institute, Södersjukhuset, Stockholm, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Nathanson
authors.affiliation: Cardiology Unit, Department of Medicine, Solna, Karolinska Institute, Stockholm, Sweden.|Capio S:t Görans Hospital, Stockholm, Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Thuresson
authors.affiliation: Statisticon AB, Uppsala, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Norhammar
authors.affiliation: Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden.
authors.forename: Jan W
authors.identifier: 0000-0002-2639-9481
authors.initials: JW
authors.lastname: Eriksson
mesh_terms: D000284:Administration, Oral; D000368:Aged; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology*; D002423:Cause of Death; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000401:mortality*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005260:Female; D005960:Glucosides / Q000627:therapeutic use*; D006801:Humans; D007003:Hypoglycemia / Q000453:epidemiology / Q000209:etiology*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D057216:Propensity Score; D016016:Proportional Hazards Models; D012042:Registries; D012307:Risk Factors; D013548:Sweden
chemical_list: D001559:Benzhydryl Compounds; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005960:Glucosides; D007004:Hypoglycemic Agents; C529054:dapagliflozin
keywords: DPP-4 inhibitor; cardiovascular disease; dapagliflozin; hypoglycaemia; pharmaco-epidemiology; type 2 diabetes