Efficacy and safety of ipragliflozin in Japanese patients with type 2 diabetes stratified by body mass index: A subgroup analysis of five randomized clinical trials

Abstract

Aims/IntroductionThe influence of overweight/obesity on the clinical efficacy and safety of sodium‐glucose co‐transporter 2 inhibitors is unclear. We carried out a pooled analysis to examine the impact of body mass index on the efficacy and safety of ipragliflozin.Materials and MethodsPatient‐level data were pooled for five Japanese double‐blind trials (NCT00621868, NCT01057628, NCT01135433, NCT01225081 and NCT01242215) in which patients were randomized to ipragliflozin or a placebo as monotherapy, or in combination with metformin, pioglitazone or a sulfonylurea. Outcomes included the changes in hemoglobin A1c, fasting plasma glucose, bodyweight and treatment‐emergent adverse events. Patients were divided into four body mass index categories.ResultsHemoglobin A1c, fasting plasma glucose and bodyweight decreased significantly in the ipragliflozin group compared with the placebo group in all body mass index categories, and in the total cohort (all P < 0.001). Hemoglobin A1c did not improve in 11.2 and 69.2% of patients in the ipragliflozin and placebo groups, respectively. The change in hemoglobin A1c was weakly correlated with the change in bodyweight in all patients (r = 0.136, P = 0.002). Regarding laboratory variables, the placebo‐subtracted difference tended to be greater in patients with higher body mass index for aspartate aminotransferase, alanine aminotransferase, γ‐glutamyl transpeptidase and uric acid. The incidences of treatment‐emergent adverse events were similar between the ipragliflozin and placebo groups in all patients combined and in the four body mass index categories.ConclusionsThese results show that the efficacy and safety of ipragliflozin are not influenced by obesity/overweight in Japanese patients.

Amelioration of fatty liver index in patients with type 2 diabetes on ipragliflozin: an association with glucose-lowering effects

“…The following indicates the strengths of this study. First, we showed that ipragliflozin ameliorated the index of hepatic steatosis in humans, although it has been reported that ipragliflozin improves the serum alanine aminotransferase levels in patients with type 2 diabetes [10][11][12]. Second, we investigated whether improvement of obesity or glucose intolerance could influence the FLI changes observed with ipragliflozin treatment.…”

Metabolic and hemodynamic effects of sodium‐dependent glucose cotransporter 2 inhibitors on cardio‐renal protection in the treatment of patients with type 2 diabetes mellitus

“…Genital infections were confirmed to have a higher incidence in an empagliflozin‐treated group (men 5.0%, women 10.0%) compared with a placebo group (men 1.5%, women 2.6%), respectively, and a canagliflozin‐treated group (men 3.8%, women 10.7%) compared with a placebo group. Pooled analysis of the incidence of genital infection in Japanese female patients showed a higher incidence in an ipragliflozin‐treated group (5.3%) compared with a placebo group (1.9%). It is generally accepted that genital infections are seen at higher frequencies in female than male diabetes patients (Table ).…”

Efficacy of ipragliflozin as monotherapy or as add‐on therapy with other oral antidiabetic medications for treating type 2 diabetes in Japanese patients with inadequate glycemic control: A subgroup analysis based on patient characteristics

“…Ipragliflozin is the first SGLT2 inhibitor to be approved for the treatment of patients with type 2 diabetes mellitus in Japan, as monotherapy or in combination with other OAM. Previous randomized placebo‐controlled studies have shown that administration of ipragliflozin to patients with type 2 diabetes mellitus improved glycemic control and had low rates of adverse events. Although treatment with SGLT2 inhibitors has been recommended for patients with type 2 diabetes mellitus who are relatively young and obese in daily clinical practice in Japan, the efficacy and safety of ipragliflozin for elderly or non‐obese patients are less clear, and there is a need to evaluate the drug based on patient background in a clinical setting.…”