Tolerability and efficacy of glycemic control with saxagliptin in older patients (aged ≥ 65 years) with inadequately controlled type 2 diabetes mellitus

Abstract

PurposeTo assess safety and efficacy of saxagliptin in older patients with type 2 diabetes mellitus (T2DM).Patients and methodsThis was a post hoc analysis of pooled data from older patients (≥65 years of age) from five 24-week phase III trials: three studies of saxagliptin versus placebo as an add-on therapy to metformin, glyburide, or a thiazolidinedione; and two studies of saxagliptin versus placebo as monotherapy in drug-naïve patients. Separate analyses were conducted on one study of initial combination therapy with saxagliptin plus metformin versus metformin monotherapy in drug-naïve patients. The safety analysis population for the five-study pool included 428 patients ≥ 65 years of age with baseline glycated hemoglobin (HbA1c) 7.0% to 10.5% who received saxagliptin 2.5 or 5 mg or placebo, and for the study of initial combination therapy included 69 patients ≥ 65 years of age with baseline HbA1c 8.0% to 12.0% who received saxagliptin 5 mg in combination with metformin or metformin monotherapy. The primary efficacy endpoint was change from baseline HbA1c.ResultsIn the five-study pool, the differences in the adjusted mean change from baseline HbA1c among older patients receiving saxagliptin versus placebo were −0.60% (95% confidence interval [CI], −0.99% to −0.21%) for saxagliptin 2.5 mg and −0.55% (−0.97% to −0.14%) for saxagliptin 5 mg; in the initial combination study, the difference was −1.22% (−2.27% to −0.17%) among older patients receiving saxagliptin 5 mg plus metformin versus metformin monotherapy. The results were generally similar in older and younger patients. Saxagliptin was well tolerated; the incidence and types of adverse events were similar for saxagliptin and comparators. Hypoglycemia was reported in 3.0% to 9.4% of patients receiving saxagliptin (0%–8.0% for comparators) and was confirmed (finger stick glucose ≤ 50 mg/dL, with associated symptoms) in 0% to 0.7% (0%–0.7% for comparators); hypoglycemic episodes did not vary by age category and did not require medical intervention.ConclusionSaxagliptin was effective and well tolerated, with a low risk of hypoglycemia, when used as monotherapy, add-on therapy, or initial combination therapy with metformin in older patients with T2DM.

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.…”

Dipeptidyl peptidase‐4 inhibitors can minimize the hypoglycaemic burden and enhance safety in elderly people with diabetes

“…Karyekar et al [59] performed a pooled analysis of studies involving saxagliptin in monotherapy as well as in combination with other oral hypoglycaemic agents in people with T2DM aged ≥65 years. The overall HbA1c reduction was −0.60% (95% CI −0.99 to −0.21%) for saxagliptin 2.5 mg and −0.55% (95% CI −0.97 to −0.14%) for saxagliptin 5 mg.…”

Emerging use of combination therapies for the management of type 2 diabetes – focus on saxagliptin and dapagliflozin

“…Safety in patients aged ≥65 years was assessed in a pooled analysis of five phase III trials, totaling 428 individuals 57. Incidence of adverse events, including hypoglycemia, was similar between treatment and placebo, and unchanged compared to younger subgroups 57.…”