Pharmacokinetics and Pharmacodynamics of Henagliflozin, a Sodium Glucose Co-Transporter 2 Inhibitor, in Chinese Patients with Type 2 Diabetes Mellitus

Xiaolan, Yong; Wen, Aidong; Liu, Xiangyang; Liu, Haiyan; Liu, Yan-Ping; Li, Nan; Hu, Tingting; Chen, Ying; Wang, Minquan; Wang, Lantian; Dai, Xiaojiao; Huang, Juan; Li, Jia; Shen, Hua-Qiong

doi:10.1007/s40261-015-0366-7

Cited by 17 publications

(11 citation statements)

References 11 publications

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“…Henagliflozin (SHR3824) is a novel, highly selective, oral inhibitor of SGLT2 12,13 . Our previous phase 2 trial (NCT02366351) showed that 12‐week treatment of henagliflozin monotherapy provided efficacious glycaemic control, reduced body weight and blood pressure, and was generally well tolerated in Chinese patients with T2D and inadequate glycaemic control with diet and exercise (data submitted for publication).…”

Section: Introductionmentioning

confidence: 99%

“…3,11 Henagliflozin (SHR3824) is a novel, highly selective, oral inhibitor of SGLT2. 12,13 Our previous phase 2 trial (NCT02366351) showed that 12-week treatment of henagliflozin monotherapy provided efficacious glycaemic control, reduced body weight and blood pressure, and was generally well tolerated in Chinese patients with T2D and inadequate glycaemic control with diet and exercise (data submitted for publication). Herein, we conducted a phase 3 trial to further evaluate the efficacy and safety of henagliflozin monotherapy in this population, with results from the 24-week placebo-controlled period and additional 28-week extension period reported.…”

Section: Introductionmentioning

confidence: 99%

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Henagliflozin monotherapy in patients with type 2 diabetes inadequately controlled on diet and exercise: A randomized, double‐blind, placebo‐controlled, phase 3 trial

Li³

et al. 2021

Diabetes Obesity Metabolism

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Aim: To evaluate henagliflozin, a novel sodium-glucose co-transporter-2 inhibitor, as monotherapy in patients with type 2 diabetes and inadequate glycaemic control with diet and exercise.Materials and Methods: This multicentre trial included a 24-week, randomized, double-blind, placebo-controlled period, followed by a 28-week extension period.Four hundred and sixty-eight patients with an HbA1c of 7.0%-10.5% were randomly assigned (1:1:1) to receive once-daily placebo, or 5 or 10 mg henagliflozin. After 24 weeks, patients on placebo were switched to 5 or 10 mg henagliflozin, and patients on henagliflozin maintained the initial therapy. The primary endpoint was the change in HbA1c from baseline after 24 weeks.Results: At Week 24, the placebo-adjusted least squares (LS) mean changes from baseline in HbA1c were −0.91% (95% CI: −1.11% to −0.72%; P < .001) and −0.94% (−1.13% to −0.75%; P < .001) with henagliflozin 5 and 10 mg, respectively; the placebo-adjusted LS mean changes were −1.3 (−1.8 to −0.9) and −1.5 (−2.0 to −1.1) kg in body weight, and −5.1 (−7.2 to −3.0) and −4.4 (−6.5 to −2.3) mmHg in systolic blood pressure (all P < .05). The trends of these improvements were sustained for an additional 28 weeks. Adverse events occurred in 81.0%, 78.9% and 78.9% of patients in the placebo, henagliflozin 5 and 10 mg groups, respectively. No diabetic ketoacidosis or major episodes of hypoglycaemia occurred.Conclusions: Henagliflozin 5 mg and 10 mg as monotherapy provided effective glycaemic control, reduced body weight and blood pressure, and was generally well tolerated.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Henagliflozin monotherapy in patients with type 2 diabetes inadequately controlled on diet and exercise: A randomized, double‐blind, placebo‐controlled, phase 3 trial

Li³

et al. 2021

Diabetes Obesity Metabolism

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“…inhibitor reduced plasma glucose level in a dose-dependent manner. No severe side effects were reported for this small group of T2DM patients with doses ranging from 5 -20 mg per day [67].…”

Section: Henagliflozinmentioning

confidence: 72%

“…The authors suggested that henagliflozin is suitable for, once daily, regimen [67]. 12 weeks, lowers postprandial glucose spike, and weight.…”

Section: Henagliflozinmentioning

confidence: 99%

An update of SGLT1 and SGLT2 inhibitors in early phase diabetes-type 2 clinical trials

Adeghate

Mohsin

Adi

et al. 2019

Expert Opinion on Investigational Drugs

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Introduction: More than 424 million adults have diabetes mellitus (DM). This number is expected to increase to 626 million by 2045. The majority (90-95%) of people with DM has type 2-diabetes (T2DM). The continued prevalence of DM and associated complications has prompted investigators to find new therapies. One of the most recent additions to the antidiabetic armamentarium are inhibitors of sodium-glucose co-transporters 1 and 2 (SGLT1, SGLT2). Areas covered: The authors review the status of SGLT2 inhibitors for the treatment of T2DM and place an emphasis on those agents in early phase clinical trials. Data and information were retrieved from American Diabetes Association, Diabetes UK, ClinicalTrials.gov, PubMed, and Scopus websites. The keywords used in the search were T2DM, SGLT1, SGLT2 and clinical trials. Expert opinion: The benefits of SGLT inhibitors include reductions in serum glycated haemoglobin (HbA1c), body weight, blood pressure and cardiovascular and renal events. However, SGLT inhibitors increase the risk of genitourinary tract infections, diabetic ketoacidosis and bone fractures. The development of SGLT inhibitors with fewer side effects and as combination therapies are the key to maximizing the therapeutic effects of this important class of anti-diabetic drug.

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“…Henagliflozin exhibited dose-proportional PK properties in both T2DM patients and healthy volunteers. 7 It can be rapidly absorbed after single-dose oral administration, with a T max of 1.5-3 h and a half-life ranging from 11 to 15 h. 8 Glimepiride, with a better safety profile than the firstgeneration sulfonylureas and prolonged action duration, is one of the most widely used sulfonylureas in the treatment of T2DM. 9 It is used as a second-line drug in conjunction with metformin or insulin 10,11 or as monotherapy used in patients who are intolerable to metformin.…”

Section: What Is K Nown and Objec Tivementioning

confidence: 99%

No apparent pharmacokinetic interactions were found between henagliflozin: A novel sodium‐glucose co‐transporter 2 inhibitor and glimepiride in healthy Chinese male subjects

Que

Huang

Xiang

et al. 2022

Clinical Pharmacy Therapeu

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What is known and objective Henagliflozin is a novel selective sodium‐glucose co‐transporter 2 (SGLT2) inhibitor with similar inhibitory effect to ertugliflozin. Glimepiride is widely used to treat type 2 diabetes mellitus (T2DM) with few cardiovascular side effects. In the present study, we aimed at evaluating the pharmacokinetic (PK) interactions between henagliflozin and glimepiride. Methods An open‐label, single‐centre, single‐arm, 3‐period, 3‐treatment, self‐control study was conducted in twelve healthy Chinese male subjects. During each study period, subjects received a single oral dose of glimepiride 2 mg, multiple oral doses of henagliflozin 10 mg or a combination of the two drugs. Serial blood samples were collected 24 h post‐dosing for PK analyses. Finger‐tip blood glucose was also tested for safety evaluation. Results and discussion Co‐administration of henagliflozin with glimepiride did not affect their plasma PK profiles. For henagliflozin, the 90% confidence intervals for the geometric mean ratio (GMR) for the maximum plasma concentrations at steady‐state (Cmax ss) and the area under the plasma concentration–time curve during a dosing interval at steady‐state (AUCτ, ss) of combination therapy to henagliflozin alone were 1.00 (0.93–1.08) and 1.00 (0.98–1.02), respectively. For glimepiride, the corresponding values of combination therapy to glimepiride alone were 1.00 (0.88–1.13) for maximum plasma concentrations (Cmax), 0.91 (0.84–0.99) for the area under the plasma concentration–time curve from 0–24 h (AUC0‐24h) and 0.91 (0.83–1.00) for the plasma concentration–time curve from 0 h to infinite (AUC0‐inf), respectively. All values fell within the equivalence range of 0.8–1.25. All monotherapies and combination therapy led to no serious adverse events and were well tolerated. What is new and conclusion Multiple doses of henagliflozin did not exert a significant change on glimepiride PK profiles and a single dose of glimepiride had little effect on henagliflozin blood concentration. Thus, henagliflozin can be co‐administered with glimepiride without dose adjustment of either drug.

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Pharmacokinetics and Pharmacodynamics of Henagliflozin, a Sodium Glucose Co-Transporter 2 Inhibitor, in Chinese Patients with Type 2 Diabetes Mellitus

Abstract: The observed pharmacokinetic and pharmacodynamic profiles of henagliflozin support a once-daily dosing regimen in Chinese T2DM patients.

Cited by 17 publications

References 11 publications

Henagliflozin monotherapy in patients with type 2 diabetes inadequately controlled on diet and exercise: A randomized, double‐blind, placebo‐controlled, phase 3 trial

Henagliflozin monotherapy in patients with type 2 diabetes inadequately controlled on diet and exercise: A randomized, double‐blind, placebo‐controlled, phase 3 trial

An update of SGLT1 and SGLT2 inhibitors in early phase diabetes-type 2 clinical trials

No apparent pharmacokinetic interactions were found between henagliflozin: A novel sodium‐glucose co‐transporter 2 inhibitor and glimepiride in healthy Chinese male subjects

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