title: Long-Term Safety of Dapagliflozin in Older Patients with Type 2 Diabetes Mellitus: A Pooled Analysis of Phase IIb/III Studies.
abstract: To evaluate the 104-week safety of dapagliflozin in older patients with type 2 diabetes mellitus.
  
  
  
  Pooled analysis assessing general safety (nine phase III studies ≤104 weeks) and cardiovascular safety (21 phase IIb/III studies ≤208 weeks) by age (<65; ≥65; ≥75 years). Patients with type 2 diabetes mellitus (±background glucose-lowering therapy) received: dapagliflozin 10 mg (n = 2026) vs. placebo (n = 1956) (nine-study pool); or dapagliflozin (2.5-50 mg; n = 5936) vs. control (placebo/comparator) (n = 3403) (21-study pool).
  
  
  
  Adverse events (AEs) and discontinuations owing to AEs were more common in older vs. younger patients, and were more frequent with dapagliflozin than placebo (AEs: <65 years: 73.1 vs. 70.7 %; ≥65 years: 77.4 vs. 73.1 %; ≥75 years: 80.4 vs. 75.3 %, respectively; discontinuations: <65 years: 5.9 vs. 5.0 %; ≥65 years: 14.4 vs. 12.2 %; ≥75 years: 26.8 vs. 22.1 %, respectively); serious AE (SAE) frequency was similar (<65 years: 11.0 vs. 11.8 %; ≥65 years: 20.0 vs. 20.2 %; ≥75 years: 19.6 vs. 18.2 %, respectively). Hypoglycaemia frequency was similar across age groups and was higher with dapagliflozin than placebo (<65 years: 18.0 vs. 13.4 %; ≥65 years: 20.2 vs. 17.7 %; ≥75 years: 17.5 vs. 16.9 %, respectively); major episodes were rare. Urinary tract infection frequency was similar between treatment groups in older patients, with no increase vs. younger patients (<65 years: 8.8 vs. 5.5 %; ≥65 years: 8.1 vs. 7.6 %; ≥75 years: 8.2 vs. 9.1 %, respectively); urinary tract infection SAEs were rare. Genital infection AEs were more common with dapagliflozin, with no increase in older patients (<65 years: 8.2 vs. 1.0 %; ≥65 years: 6.6 vs. 0.9 %; ≥75 years: 7.2 vs. 0.0 %, respectively) and no SAEs. Volume reduction AEs were uncommon, with a higher frequency with dapagliflozin vs. placebo and in patients ≥75 years (<65 years: 1.7 vs. 1.2 %; ≥65 years: 2.3 vs. 1.7 %; ≥75 years: 3.1 vs. 2.6 %, respectively). Dapagliflozin did not increase the risk of fractures (<65 years: 1.1 vs. 1.1 %; ≥65 years: 1.1 vs. 2.7 %; ≥75 years: 1.0 vs. 2.6 %, respectively) or falls (<65 years: 0.7 vs. 0.7 %; ≥65 years: 0.6 vs. 2.1 %; ≥75 years: 0.0 vs. 1.3 %, respectively), regardless of age. AEs of renal function were more common with dapagliflozin than placebo and increased with age (<65 years: 3.5 vs. 2.3 %; ≥65 years: 14.0 vs. 7.9 %; ≥75 years: 29.9 vs. 20.8 %, respectively). Most were non-serious small transient increases in serum creatinine. Dapagliflozin did not increase cardiovascular risk regardless of age [hazard ratio (95 % confidence interval) vs.
  
  
  
  <65 years: 0.726 (0.473, 1.114); ≥65 years: 0.879 (0.565, 1.366); ≥75 years: 0.950 (0.345, 2.617), respectively].
  
  
  
  Dapagliflozin treatment up to 104 weeks was well tolerated in older patients. Older dapagliflozin-treated patients had more renal AEs than placebo-treated patients; the majority of which were non-serious small transient changes in serum creatinine.
authors.affiliation: Department of Medicine, University of Padova, Via Giustiniani 2, Padua, 35128, Italy. paola.fioretto@unipd.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Fioretto
authors.affiliation: AstraZeneca, Fort Washington, PA, USA.
authors.forename: Traci A
authors.initials: TA
authors.lastname: Mansfield
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Agata
authors.initials: A
authors.lastname: Ptaszynska
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.|Johnson & Johnson, Raritan, NJ, USA.
authors.forename: Yshai
authors.initials: Y
authors.lastname: Yavin
authors.affiliation: AstraZeneca, Gothenburg, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Johnsson
authors.affiliation: AstraZeneca, Gaithersburg, MD, USA.
authors.forename: Shamik
authors.initials: S
authors.lastname: Parikh
mesh_terms: D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D050723:Fractures, Bone / Q000139:chemically induced / Q000453:epidemiology; D005960:Glucosides / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012449:Safety; D014552:Urinary Tract Infections / Q000139:chemically induced / Q000453:epidemiology
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; C529054:dapagliflozin