Efficacy and safety of canagliflozin compared with placebo in older patients with type 2 diabetes mellitus: a pooled analysis of clinical studies

Abstract

BackgroundCanagliflozin is a sodium glucose co-transporter 2 inhibitor developed for the treatment of patients with type 2 diabetes mellitus (T2DM). The efficacy and safety of canagliflozin were evaluated in patients with T2DM <65 and ≥65 years of age.MethodsPooled data from 4 randomised, placebo-controlled, 26-week, Phase 3 studies (N = 2,313) evaluating canagliflozin 100 and 300 mg were analysed by age: <65 years (n = 1,868; mean age, 52.8 years) or ≥65 years (n = 445; mean age, 69.3 years). Efficacy evaluations included change from baseline in glycaemic parameters and systolic blood pressure (BP), and percent change from baseline in body weight. Assessment of safety/tolerability included adverse event (AE) reports, incidence of documented hypoglycaemia, and percent change from baseline in fasting plasma lipids.ResultsCanagliflozin 100 and 300 mg reduced HbA1c and fasting plasma glucose relative to placebo in patients <65 and ≥65 years of age. Both canagliflozin doses reduced body weight and systolic BP relative to placebo in patients <65 and ≥65 years of age. Incidence of overall AEs was similar across all treatment groups in patients <65 and ≥65 years of age. Incidences of serious AEs and AE-related discontinuations were similar across all treatment groups in patients <65 years of age and higher with canagliflozin 100 mg than other groups in patients ≥65 years of age. As in patients <65 years of age, incidences of genital mycotic infections and osmotic diuresis-related AEs were higher with canagliflozin relative to placebo in those ≥65 years of age. Incidences of urinary tract infections (UTIs), renal-related AEs, AEs related to volume depletion, and documented hypoglycaemia episodes were similar across all treatment groups in patients ≥65 years of age; no notable trends were observed with canagliflozin 100 and 300 mg relative to placebo in these AEs among patients <65 years of age. Changes in lipid parameters with canagliflozin were similar in both age subsets.ConclusionsCanagliflozin improved glycaemic control, body weight, and systolic BP, and was generally well tolerated in older patients with T2DM.Trial registrationClinicalTrials.gov, NCT01081834; NCT01106677; NCT01106625; NCT01106690.

Real-world evidence for the safety of ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus (STELLA-ELDER): final results of a post-marketing surveillance study

“…These findings are consistent with those of a pooled analysis of patients treated with 100 mg canagliflozin, 300 mg canagliflozin, or placebo/active comparators [22], where volume depletion-related AEs occurred in 4.9%, 8.7%, and 2.6% of 8949 patients aged ≥75 years, respectively, compared with 2.2%, 3.1%, and 1.4% of 490 patients aged <75 years. The risk of volume depletion-related AEs in canagliflozin-treated patients was higher in patients aged ≥65 years than in younger patients [23].…”

Canagliflozin: A Review in Type 2 Diabetes

“…However, glycaemic improvements were slightly more pronounced in the younger patient groups [50,51].…”

“…In older patients (n = 714) aged 55-80 years with T2D inadequately controlled by oral/injectable AHA regimens, adding canagliflozin 100 or 300 mg/day significantly (p < 0.001) improved glycaemic control over 26 Notably, canagliflozin (as monotherapy or combination therapy) improved glycaemic control versus placebo regardless of whether patients were aged ≥65 or <65 years (n = 445 and 1868) [50] or ≥75 or <75 years (n = 183 and 3975) [51] in pooled analyses of four [50] or six [51] phase 3 trials (plus CANVAS substudies [51]) of 18-26 weeks' duration. However, glycaemic improvements were slightly more pronounced in the younger patient groups [50,51].…”

Comparative analysis of quality of life in patients treated with canagliflozine or DPP-IV inhibitor

“…Его эффективность и безопасность были продемонстрированы в серии контролируемых клинических исследований в составе моно-, двойной и тройной терапии, а также в комбина-ции с инсулином [10][11][12][13][14][15][16][17][18][19][20][21] у пациентов с СД2 при разной длительности заболевания [17] и в целом -различных возрастных групп, в том числе и у лиц пожилого и стар-ческого возраста [13,16]. Однако, касательно послед-него, необходимо отметить, что в работе Bode B.…”

“…[16] вероятность развития различных нежелательных явле-ний у пациентов 55-80 лет была немного выше в группах канаглифлозина 300 и 100 мг/сут в сравнении с плацебо, а в исследовании Sinclair A. и соавт. [13] -сопоставима с плацебо, но несколько чаще становилась причиной вы-бытия из исследования в группе канаглифлозина. В этой связи инструкция к применению препарата указывает на необходимость более осторожного применения ка-наглифлозина у пациентов старших возрастных групп для снижения риска развития нежелательных явлений, одним из наиболее значимых среди которых является де-гидратация.…”