Safety and efficacy of ertugliflozin in Asian patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy: VERTIS Asia

Ji, Linong; Liu, Yanmei; Miao, Heng; Xie, Yonghui; Yang, Ming; Wang, Wei; Mu, Yuting; Yan, Ping; Pan, Sharon; Lauring, Brett; Liu, Shu; Huyck, Susan; Qiu, Yanping; Terra, Steven G.

doi:10.1111/dom.13681

Cited by 40 publications

(58 citation statements)

References 24 publications

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“…There were no reports of severe hypoglycaemia in the E/SE Asian population. The observed safety profile is consistent with the overall safety data that have been published for ertugliflozin to date …”

Section: Discussionsupporting

confidence: 89%

“…The efficacy findings are also consistent with those reported in a meta- profile is consistent with the overall safety data that have been published for ertugliflozin to date. 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.…”

Section: Safetymentioning

confidence: 83%

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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: 89%

Section: Safetymentioning

confidence: 83%

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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“…The PK findings reported here in Chinese subjects residing in China are comparable with those observed in other populations and are supported by results from a recently conducted phase 3 study exploring the efficacy and safety of ertugliflozin in Asian patients with T2DM . This longer‐term study (with the same ertugliflozin doses of 5 mg and 15 mg assessed in the current phase 1 study) demonstrated that ertugliflozin improved glycemic control and reduced body weight and systolic blood pressure in Asian patients with T2DM inadequately controlled on metformin monotherapy, including Chinese patients from mainland China . Taken together, the comparable efficacy and safety across the ertugliflozin phase 3 studies in varied populations including Chinese patients and the PK findings from the phase 1 studies suggest no clinically meaningful PK differences, and no dose modification of ertugliflozin is required based on race or body weight.…”

Section: Discussionsupporting

confidence: 86%

Pharmacokinetic Properties of Single and Multiple Doses of Ertugliflozin, a Selective Inhibitor of SGLT2, in Healthy Chinese Subjects

Shi

et al. 2019

Clinical Pharm in Drug Dev

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Ertugliflozin, a sodium-glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus, prevents renal glucose reabsorption resulting in urinary glucose excretion. This open-label, parallel cohort, randomized study conducted in healthy Chinese adults residing in China assessed the pharmacokinetics, tolerability, and safety of 5 mg and 15 mg of ertugliflozin following single (fasted condition) and multiple-dose (fed condition) administration. Sixteen subjects were randomized and completed the study. Ertugliflozin absorption was rapid, with maximum plasma concentrations observed 1 hour after dosing under fasted conditions and 2 to 4 hours after dosing under fed conditions. Following single-and multiple-dose administration, ertugliflozin exhibited dose-proportional exposures with an apparent mean terminal halflife of approximately 9.5 to 11.9 hours. Steady state was reached after 4 once-daily doses. The accumulation ratio based on the area under the plasma concentration-time curve after multiple-dose administration was approximately 1.3 and 1.2 for ertugliflozin 5 mg and 15 mg, respectively. Ertugliflozin was generally well tolerated following administration of single and multiple oral doses of 5 mg and 15 mg in healthy Chinese subjects. Pharmacokinetic comparison with non-Asian subjects indicated that there are no clinically meaningful racial differences and no dose modification of ertugliflozin is required based on race or body weight.

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“…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.…”

Section: Resultsmentioning

confidence: 99%

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

Kamalinia

Josse

Donio

et al. 2019

Endocrino Diabet & Metabol

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Objectives: For patients with type 2 diabetes, newer antihyperglycaemic agents (AHA), including the dipeptidyl peptidase IV inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium glucose co-transporter 2 inhibitors (SGLT2i) offer a lower risk of hypoglycaemia relative to sulfonylurea or insulin.However, it is not clear how AHA compare to placebo on risk of any hypoglycaemia.This study evaluates the risk of any and severe hypoglycaemia with AHA and metformin relative to placebo. Design: A systematic review and meta-analysis was conducted of randomized, placebo-controlled trials ≥12 weeks in duration. MEDLINE, Embase and the Cochrane Library were searched up to April 16, 2019. Studies allowing use of other diabetes medications were excluded. Mantel-Haenszel risk ratio with 95% confidence intervals were used to pool estimates based on class of AHA and number of concomitant therapies used.Patients: Eligible studies enrolled patients with type 2 diabetes ≥18 years of age.Results: 144 studies met our inclusion criteria. Any hypoglycaemia was not increased with AHA when used as monotherapy (DPP4i (RR 1.12; 95% CI 0.81-1.56), GLP1RA (1.77; 0.91-3.46), SGLT2i (1.34; 0.83-2.15)), or as add-on to metformin (DPP4i (0.95; 0.67-1.35), GLP1RA (1.24; 0.80-1.91), SGLT2i (1.29; 0.91-1.83)) or as triple therapy (1.13; 0.67-1.91). However, metformin monotherapy (1.73; 1.02-2.94) and dual therapy initiation (3.56; 1.79-7.10) was associated with an increased risk of any hypoglycaemia. Severe hypoglycaemia was rare not increased for any comparisons. Conclusions:Metformin and the simultaneous initiation of dual therapy, but not AHA used alone or as single add-on combination therapy, was associated with an increased risk of any hypoglycaemia relative to placebo. K E Y W O R D S diabetes mellitus, type 2, dipeptidyl peptidase IV inhibitor, glucagon-like peptide-1 receptor agonist, hypoglycaemia, sodium glucose co-transporter 2 inhibitor S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Kamalinia S, Josse RG, Donio PJ, Leduc L, Shah BR, Tobe SW. Risk of any hypoglycaemia with newer antihyperglycaemic agents in patients with type 2 diabetes: A systematic review and meta-analysis. Endocrinol Diab Metab. 2020;3:e00100. https ://doi.

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Safety and efficacy of ertugliflozin in Asian patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy: VERTIS Asia

Cited by 40 publications

References 24 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

Pharmacokinetic Properties of Single and Multiple Doses of Ertugliflozin, a Selective Inhibitor of SGLT2, in Healthy Chinese Subjects

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

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