title: Long-term safety and tolerability of saxagliptin add-on therapy in older patients (aged ≥ 65 years) with type 2 diabetes.
abstract: BACKGROUND
  Treatment decisions for older patients with type 2 diabetes mellitus must balance glycemic control and adverse event risk. The objective of this study was to evaluate the long-term safety and tolerability of saxagliptin 5 mg as add-on therapy to common antihyperglycemic drugs in patients aged ≥ 65 years and <65 years.
  
  
  METHODS
  Pooled adverse event data from three placebo-controlled trials of 76-206 weeks' duration in older (≥ 65 years) and younger (<65 years) patients receiving saxagliptin 5 mg or matching placebo added to metformin, glyburide, or a thiazolidinedione were analyzed. Measurements were calculated from day of first dose to specified event or last dose and included time at risk for adverse events, treatment-related adverse events, serious adverse events, adverse events leading to discontinuation, and events of special interest. Weighted incidence rates (number of events/total time) and incidence rate ratios (saxagliptin/placebo) with 95% confidence intervals were calculated (Mantel-Haenszel test).
  
  
  RESULTS
  A total of 205 older (mean age 69 years; saxagliptin, n=99; placebo, n=106) and 1,055 younger (mean age 52 years; saxagliptin, n=531; placebo, n=524) patients were assessed. Regardless of age category, the adverse event incidence rates were generally similar between treatments, with confidence intervals for incidence rate ratios bridging 1. Treatment-related adverse events occurred in 36 older patients receiving saxagliptin versus 32 receiving placebo (incidence rate 34.1 versus 27.1 per 100 person-years) and in 150 younger patients in both treatment groups (incidence rate 24.0 versus 27.8 per 100 person-years). With saxagliptin versus placebo, serious adverse events occurred in eight versus 14 older (incidence rate 5.7 versus 9.9 per 100 person-years) and 49 versus 44 younger patients (incidence rate 6.5 versus 6.6 per 100 person-years). There were two deaths (one patient ≥ 65 years) with saxagliptin and six (none aged ≥ 65 years) with placebo. Older patients rarely experienced symptomatic confirmed hypoglycemia (fingerstick glucose ≤ 50 mg/dL; saxagliptin, n=1; placebo, n=2).
  
  
  CONCLUSIONS
  Saxagliptin add-on therapy was generally well tolerated in older patients aged ≥ 65 years with type 2 diabetes mellitus, with a long-term safety profile similar to that of placebo.
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Nayyar
authors.initials: N
authors.lastname: Iqbal
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Elsie
authors.initials: E
authors.lastname: Allen
authors.affiliation: AstraZeneca, Wilmington, DE, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Öhman
mesh_terms: D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives*; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004151:Dipeptides / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D054795:Incretins / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D004151:Dipeptides; D054795:Incretins; D010919:Placebos; C502994:saxagliptin; D000218:Adamantane
keywords: glyburide; metformin; older patients; saxagliptin; thiazolidinedione