Long-term safety and tolerability of saxagliptin add-on therapy in older patients (aged ≥65 years) with type 2 diabetes

Abstract

BackgroundTreatment 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.MethodsPooled 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).ResultsA 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).ConclusionSaxagliptin 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.

Efficacy and safety of saxagliptin monotherapy or added to metformin in Chinese patients with type 2 diabetes mellitus: results from the 24‐week, post‐marketing SUNSHINE study

“…Results from global Phase III clinical studies have demonstrated that a dosage of 5 mg once daily can significantly decrease HbA1c and FPG and PPG concentrations in patients with T2DM . Moreover, saxagliptin has proved to be well tolerated in patients with T2DM, including those with renal impairment and elderly patients (≥65 years of age) …”

“…5,[8][9][10][11] Moreover, saxagliptin has proved to be well tolerated in patients with T2DM, including those with renal impairment 12,13 and elderly patients (≥65 years of age). 14,15 Saxagliptin was approved in China in May 2011 for the treatment of T2DM, either as monotherapy or added to metformin. Although several studies of saxagliptin have been undertaken in China, [16][17][18] there is still a lack of data supporting its efficacy and safety from large-scale clinical trials in Chinese patients.…”

Clinical Pharmacokinetics and Pharmacodynamics of Saxagliptin, a Dipeptidyl Peptidase-4 Inhibitor

“…Neither age nor sex was identified as a significant covariate in the apparent clearance of saxagliptin or 5-hydroxy saxagliptin in population pharmacokinetic analyses [7,33]. The \2-fold difference in saxagliptin systemic exposure between older and young individuals and the favourable safety and tolerability profile observed in people C65 years old when saxagliptin was used as monotherapy or add-on therapy [34][35][36][37] suggest that age alone does not warrant dose adjustment. The small difference in 5-hydroxy saxagliptin exposure in female subjects compared with male subjects does not warrant dose adjustment.…”

Características diferenciales de la diabetes mellitus tipo 2 en el paciente anciano. Papel de los inhibidores de la dipeptidil peptidasa 4

“…Disponemos ya de estudios en personas mayores de todos ellos que apoyan su eficacia hipoglicemiante y seguridad [67][68][69][70][71][72][73] . Tres de estos estudios se realizaron en pacientes con 70 o más años de edad 67,68,73 .…”