Efficacy and safety of ipragliflozin as an add‐on therapy to sitagliptin and metformin in Korean patients with inadequately controlled type 2 diabetes mellitus: A randomized controlled trial

Abstract

AimTo evaluate the efficacy and safety of ipragliflozin vs placebo as add‐on therapy to metformin and sitagliptin in Korean patients with type 2 diabetes mellitus (T2DM).MethodsThis double‐blind, placebo‐controlled, multi‐centre, phase III study was conducted in Korea in 2015 to 2017. Patients were randomized to receive either ipragliflozin 50 mg/day or placebo once daily for 24 weeks in addition to metformin and sitagliptin. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to end of treatment (EOT).ResultsIn total, 143 patients were randomized and 139 were included in efficacy analyses (ipragliflozin: 73, placebo: 66). Baseline mean (SD) HbA1c levels were 7.90 (0.69)% for ipragliflozin add‐on and 7.92 (0.79)% for placebo. The corresponding mean (SD) changes from baseline to EOT were −0.79 (0.59)% and 0.03 (0.84)%, respectively, in favour of ipragliflozin (adjusted mean difference −0.83% [95% CI −1.07 to −0.59]; P < .0001). More ipragliflozin‐treated patients than placebo‐treated patients achieved HbA1c target levels of <7.0% (44.4% vs 12.1%) and < 6.5% (12.5% vs 1.5%) at EOT (P < .05 for both). Fasting plasma glucose, fasting serum insulin, body weight and homeostatic model assessment of insulin resistance decreased significantly at EOT, in favour of ipragliflozin (adjusted mean difference −1.64 mmol/L, −1.50 μU/mL, −1.72 kg, and −0.99, respectively; P < .05 for all). Adverse event rates were similar between groups (ipragliflozin: 51.4%; placebo: 50.0%). No previously unreported safety concerns were noted.ConclusionsIpragliflozin as add‐on to metformin and sitagliptin significantly improved glycaemic variables and demonstrated a good safety profile in Korean patients with inadequately controlled T2DM.

Risk of any hypoglycaemia with newer antihyperglycaemic agents in patients with type 2 diabetes: A systematic review and meta‐analysis

“…Of the 22 089 hits retrieved from our search, 144 studies met our inclusion criteria (Figure ). An agreement value ( κ ) of 80% was achieved for studies requiring detailed analysis and extraction.…”

“…Almost all (140/144) studies reported on drop‐out rates between treatment arms. Of these, one third of studies (42/140 or 30%) were considered high risk of attrition bias, either due to a higher drop‐out rates in the treatment compared to placebo arms or specific mention of participant study withdrawal due to hypoglycaemia . Six studies were found to have a high risk of bias for selective reporting, either for providing only a range of hypoglycaemia outcomes or reporting hypoglycaemia data only for the extension phase or insufficient details on the severity of episodes …”

Efficacy of Modern Diabetes Treatments DPP-4i, SGLT-2i, and GLP-1RA in White and Asian Patients With Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials

“… Forest plot for white- and Asian-dominant groups for SGLT-2i. See references 50 – 65 for complete citations. …”

Inclusion of Ipragliflozin into the Vital and Essential Drugs List: Budget Impact Analysis

“…Также не учитывалась возможность повышения дозы ипраглифлозина с 50 мг до 100 мг в день. Это допущение было основано на том, что в РКИ, в которых изучалась эффективность и безопасность ипраглифлозина при СД 2 типа, титрация ипраглифлозина до 100 мг у пациентов, которым она была необходима, изучалась в основном во второй части исследования, которая проводилась как открытое исследование [13,14]. В единственном РКИ, где титрация дозы до 100 мг проводилась во втором периоде исследования при сохранении дизайна РКИ (пациентам, не достигшим уровня HbA1c < 7%, был добавлен ипраглифлозин 50 мг без ослепления, при этом была продолжена терапия, которую они получали исходно, с сохранением ослепления), статистически значимых изменений по среднему уровню HbA1c в группе, получавшей в результате ипраглифлозин в дозе 100 мг, выявлено не было, хотя еще 12% пациентов (9 из 69 в данной группе) достигли уровня HbA1c < 7% 9 .…”

“…В 2019 году был зарегистрирован новый препарат, относящийся к иНГЛТ-2 -ипраглифлозин. Его эффективность и безопасность в монотерапии и в комбинации с другими сахароснижающими препаратами была продемонстрирована в ряде исследований [5][6][7][8][9][10][11][12][13][14]. Включение данного препарата в перечень жизненно необходимых и важнейших лекарственных препаратов (ЖНВЛП) потенциально может расширить возможности доступа пациентов с СД 2 типа к данной группе препаратов.…”