Safety and tolerability of empagliflozin in East Asian patients with type 2 diabetes: Pooled analysis of phase I–<scp>III</scp> clinical trials

Yabe, Daisuke; Yasui, Atsutaka; Ji, Linong; Lee, Moon‐Kyu; Ma, Rong; Chang, Tien-Jyun; Okamura, Tomoo; Zeller, Cordula; Kaspers, Stefan; Lee, Sang Hoon; Köhler, Sven; Seino, Yutaka

doi:10.1111/jdi.12910

Cited by 30 publications

(34 citation statements)

References 52 publications

(74 reference statements)

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“…Previous reports have noted that Asian populations have a lower BMI compared with Western populations, but the increased risk of T2DM starts at a lower BMI in Asian compared with Western patients . The baseline BMI in the E/SE Asian population in this current analysis is similar to studies of other SGLT2 inhibitors in Asian and E/SE Asian populations (25.5 to 26.0 kg/m 2 ) …”

Section: Discussionsupporting

confidence: 72%

“…The safety and tolerability of another SGLT2 inhibitor, empagliflozin, in East Asian patients with T2DM are reported in a pooled analysis based on >2100 patient-years' exposure. 19 Empagliflozin was generally well tolerated in this population with a similar safety profile in terms of general AEs and prespecifed AEs to those described here with ertugliflozin. Incidences of hypoglycaemia differed according to baseline antihyperglycaemic medication, with a higher risk in patients on background sulphonylurea therapy as expected because of the associated stimulation of insulin secretion.…”

Section: Safetysupporting

confidence: 59%

“…The safety and tolerability of another SGLT2 inhibitor, empagliflozin, in East Asian patients with T2DM are reported in a pooled analysis based on >2100 patient‐years’ exposure . Empagliflozin was generally well tolerated in this population with a similar safety profile in terms of general AEs and prespecifed AEs to those described here with ertugliflozin.…”

Section: Discussionmentioning

confidence: 75%

“…9,[11][12][13][14][15]25 East/SE Asian patients included in the current analysis of ertugliflozin efficacy had normal baseline renal function with a baseline eGFR similar to studies of other SGLT2 inhibitors in Asian and E/SE Asian populations (85.9 to 95.3 mL/min/m 2 ). 19,20 A small initial decrease from baseline in eGFR was observed with ertugliflozin in the E/SE Asian population in the placebo pool and active-comparator study that returned to baseline over time. These results are consistent with findings from other studies in the VERTIS phase 3 programme and this pattern of eGFR change from baseline is common among SGLT2 inhibitors.…”

Section: Safetymentioning

confidence: 98%

“…In the placebo pool, few patients in the E/SE Asian population had documented hypoglycaemia and the incidence with ertugliflozin 19,20 T A B L E 2 Summary of overall safety and prespecified adverse events (AEs) in the East and Southeast (E/SE) Asian and non-E/SE Asian populations: broad pool (all subjects as treated population, including rescue approach a ) A greater reduction from baseline in SBP was observed with ertugliflozin treatment compared with placebo and glimepiride in the E/SE Asian population. The SBP lowering may be of particular relevance in East Asia, given the high burden of stroke in this region.…”

Section: Safetymentioning

confidence: 99%

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Efficacy and safety of ertugliflozin in East/Southeast Asian patients with type 2 diabetes mellitus

Liu

Patel

Cater

et al. 2020

Diabetes Obesity Metabolism

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Aim Post‐hoc analysis of the efficacy and safety of ertugliflozin in East/Southeast (E/SE) Asian patients with type 2 diabetes mellitus (T2DM). Materials and Methods Efficacy evaluations used data from randomized, double‐blind, phase 3 studies: a pool of two 26‐week placebo‐controlled studies and one 52‐week active‐comparator (glimepiride) study. Least squares mean change from baseline was calculated for HbA1c, fasting plasma glucose (FPG), body weight (BW) and systolic blood pressure (SBP). Safety evaluation included overall and prespecified adverse events based on pooled data (broad pool) from seven phase 3 studies (including studies in the efficacy analysis). Results Among 161 E/SE Asian patients in the placebo pool (ertugliflozin, n = 106), ertugliflozin reduced HbA1c, FPG, BW and SBP from baseline at week 26. The placebo‐adjusted changes from baseline for ertugliflozin 5 and 15 mg were: HbA1c, −0.9% and −1.0%; BW, −2.1 and −1.9 kg; and SBP, –3.3 and −3.5 mmHg, respectively. Among 174 E/SE Asian patients in the active‐comparator study (ertugliflozin, n = 118), HbA1c changes from baseline at week 52 were −0.6%, −0.6% and −0.7% for ertugliflozin 5 mg, 15 mg and glimepiride, respectively. Ertugliflozin 5 and 15 mg reduced BW from baseline by −4.3 and −4.1 kg, respectively, and SBP by −7.4 and −9.3 mmHg, respectively, compared with glimepiride. Safety findings were generally consistent with overall ertugliflozin safety data published to date. Conclusions Treatment with ertugliflozin was associated with reductions in HbA1c, FPG, BW and SBP, and was generally well tolerated in E/SE Asian patients with T2DM. https://ClinicalTrials.gov identifier: NCT01986855, NCT01999218, NCT01958671, NCT02099110, NCT02036515, NCT02033889, NCT02226003.

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Section: Discussionsupporting

confidence: 72%

Section: Safetysupporting

confidence: 59%

Section: Discussionmentioning

confidence: 75%

Section: Safetymentioning

confidence: 98%

Section: Safetymentioning

confidence: 99%

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Efficacy and safety of ertugliflozin in East/Southeast Asian patients with type 2 diabetes mellitus

Liu

Patel

Cater

et al. 2020

Diabetes Obesity Metabolism

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Population Pharmacokinetic Analyses of Ertugliflozin in Select Ethnic Populations

Fediuk

Sahasrabudhe

Dawra

et al. 2021

Clinical Pharm in Drug Dev

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Ertugliflozin, a sodium‐glucose cotransporter 2 inhibitor, is approved for treatment of type 2 diabetes. Two population pharmacokinetic (PK) analyses were conducted, using data from up to 17 phase 1 to 3 studies, to characterize ertugliflozin PK parameters in select ethnic subgroups: (1) East/Southeast (E/SE) Asian vs non‐E/SE Asian subjects; (2) Asian subjects from mainland China vs Asian subjects from the rest of the world and non‐Asian subjects. A 2‐compartment model with first‐order absorption, lag time, and first‐order elimination was fitted to the observed data. For the E/SE Asian vs non‐E/SE Asian analysis (13 692 PK observations from 2276 subjects), E/SE Asian subjects exhibited a 17% increase in apparent clearance (CL/F) and 148% increase in apparent central volume of distribution (Vc/F) vs non‐E/SE Asian subjects. However, individual post hoc CL/F values were similar between groups when body weight differences were considered. For the second analysis (16 018 PK observations from 2620 subjects), compared with non‐Asian subjects, CL/F was similar while Vc/F increased by 44% in Asian subjects from mainland China and both CL/F and Vc/F increased in Asian subjects from the rest of the world (8% and 115%, respectively) vs non‐Asian subjects. Increases in Vc/F would decrease the ertugliflozin maximum concentration but would not impact area under the concentration‐time curve. Therefore, the differences in CL/F (area under the concentration‐time curve) and Vc/F were not considered clinically relevant or likely to result in meaningful ethnic differences in the PK of ertugliflozin.

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Cardiovascular and renal effectiveness of empagliflozin in routine care in East Asia: Results from the EMPRISE East Asia study

Seino

Kim

Yabe

et al. 2020

Endocrino Diabet & Metabol

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Aim To evaluate the effectiveness of empagliflozin in clinical practice in East Asia in the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) East Asia study. Materials and methods Data were obtained from the Medical Data Vision database (Japan), National Health Insurance Service database (South Korea) and National Health Insurance database (Taiwan). Patients aged ≥ 18 years with type 2 diabetes initiating empagliflozin or a dipeptidyl peptidase‐4 (DPP‐4) inhibitor were 1:1 propensity score (PS) matched into sequentially built cohorts of new users naïve to both drug classes. This design reduces confounding due to switching treatments, time lag and immortal time biases. Outcomes included hospitalization for heart failure (HHF), end‐stage renal disease (ESRD) and all‐cause mortality. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional models, controlling for > 130 baseline characteristics in each data source and pooled by random‐effects meta‐analysis. Results Overall, 28 712 pairs of PS‐matched patients were identified with mean follow‐up of 5.7‐6.8 months. Compared with DPP‐4 inhibitors, the risk of HHF was reduced by 18% and all‐cause mortality was reduced by 36% with empagliflozin (HR 0.82; 95% CI 0.71‐0.94, and HR 0.64; 95% CI 0.50‐0.81, respectively). Reductions were consistent across countries, and in patients with and without baseline cardiovascular disease. ESRD was also significantly reduced with empagliflozin versus DPP‐4 inhibitors (HR 0.37; 95% CI 0.24‐0.58). Conclusions Empagliflozin treatment was associated with reduced risk for HHF, all‐cause mortality and ESRD compared with DPP‐4 inhibitors in routine clinical practice in Japan, South Korea and Taiwan.

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Safety and tolerability of empagliflozin in East Asian patients with type 2 diabetes: Pooled analysis of phase I–III clinical trials

Abstract: In the present pooled analysis, EMPA was well tolerated in East Asian type 2 diabetes patients based on >2,100 patient-years' exposure, consistent with results from the overall analysis population.

Cited by 30 publications

References 52 publications

Efficacy and safety of ertugliflozin in East/Southeast Asian patients with type 2 diabetes mellitus

Efficacy and safety of ertugliflozin in East/Southeast Asian patients with type 2 diabetes mellitus

Population Pharmacokinetic Analyses of Ertugliflozin in Select Ethnic Populations

Cardiovascular and renal effectiveness of empagliflozin in routine care in East Asia: Results from the EMPRISE East Asia study

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