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

Que, Linling; Huang, Kai; Xiang, Xuemei; Ding, Ying; Chu, Nan-Nan; Qing, HE

doi:10.1111/jcpt.13659

Cited by 4 publications

(3 citation statements)

References 21 publications

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“…Other new similar compounds (Ipragliflozin, Luseogliflozin, Tofogliflozin, and Remogliflozin) are investigated in clinical studies. The most recent SGLT inhibitors are investigated using pharmacokinetic and pharmacodynamic analyses (Remoglicoflozin [36][37][38][39], Henaglicoflozin [40][41][42][43], and Licoglicoflozin [44][45][46][47]).…”

Section: Sglt-2 Inhibitors In Dm Therapymentioning

confidence: 99%

Risks and Benefits of SGLT-2 Inhibitors for Type 1 Diabetes Patients Using Automated Insulin Delivery Systems—A Literature Review

Elian,

Popovici,

Karampelas

et al. 2024

IJMS

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The primary treatment for autoimmune Diabetes Mellitus (Type 1 Diabetes Mellitus-T1DM) is insulin therapy. Unfortunately, a multitude of clinical cases has demonstrated that the use of insulin as a sole therapeutic intervention fails to address all issues comprehensively. Therefore, non-insulin adjunct treatment has been investigated and shown successful results in clinical trials. Various hypoglycemia-inducing drugs such as Metformin, glucagon-like peptide 1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, amylin analogs, and Sodium-Glucose Cotransporters 2 (SGLT-2) inhibitors, developed good outcomes in patients with T1DM. Currently, SGLT-2 inhibitors have remarkably improved the treatment of patients with diabetes by preventing cardiovascular events, heart failure hospitalization, and progression of renal disease. However, their pharmacological potential has not been explored enough. Thus, the substantial interest in SGLT-2 inhibitors (SGLT-2is) underlines the present review. It begins with an overview of carrier-mediated cellular glucose uptake, evidencing the insulin-independent transport system contribution to glucose homeostasis and the essential roles of Sodium-Glucose Cotransporters 1 and 2. Then, the pharmacological properties of SGLT-2is are detailed, leading to potential applications in treating T1DM patients with automated insulin delivery (AID) systems. Results from several studies demonstrated improvements in glycemic control, an increase in Time in Range (TIR), a decrease in glycemic variability, reduced daily insulin requirements without increasing hyperglycemic events, and benefits in weight management. However, these advantages are counterbalanced by increased risks, particularly concerning Diabetic Ketoacidosis (DKA). Several clinical trials reported a higher incidence of DKA when patients with T1DM received SGLT-2 inhibitors such as Sotagliflozin and Empagliflozin. On the other hand, patients with T1DM and a body mass index (BMI) of ≥27 kg/m2 treated with Dapagliflozin showed similar reduction in hyperglycemia and body weight and insignificantly increased DKA incidence compared to the overall trial population. Additional multicenter and randomized studies are required to establish safer and more effective long-term strategies based on patient selection, education, and continuous ketone body monitoring for optimal integration of SGLT-2 inhibitors into T1DM therapeutic protocol.

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Section: Sglt-2 Inhibitors In Dm Therapymentioning

confidence: 99%

Risks and Benefits of SGLT-2 Inhibitors for Type 1 Diabetes Patients Using Automated Insulin Delivery Systems—A Literature Review

Elian,

Popovici,

Karampelas

et al. 2024

IJMS

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“…In terms of increasing the risk of urinary tract infection,henagli ozin has a better safety pro le than dapagli ozin, empagli ozin and canagli ozin.Hengagli ozin is mainly metabolized by UGT2B4/7, UGT1A9, UGT1A3, and UGT1A6, and is a substrate for BCRP and P-gp transporters. There were no drug interactions between hengagli ozin and metformin, glibenclamide, valsartan and warfarin that affected clinical application [34,[38][39][40] . Exposure to hengagli ozin was reduced when hengagli ozin was combined with rifampin.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic interactions between donafenib and empagliflozin or henagliflozin , lenvatinib and empagliflozin or henagliflozin in rats

Liu,

Du,

Wang

et al. 2024

Preprint

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Donafenib(DONA) and lenvatinib(LEN) are small-molecule tyrosine kinase inhibitors(TKI) that are used to treat advanced hepatocellular carcinoma(HCC).Empagliflozin and henagliflozin are sodium-glucose cotransporter 2(T2DM) inhibitors that are used to treat type 2 diabetes(T2DM).Empagliflozin and henaglifiozin are uridine diphosphate glucuronosyltransferase(UGT)1A9, Substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP)Donafenib is metabolized by UGT1A9 and is an inhibitor of UGT1A9 and lenvatinib is a substrate for P-gp and BCRP.T2DM is one of the risk factors for HCC progression, so the two drugs may be used in combination in clinical practice, but there is a lack of clear information about drug interactions. Therefore, the present study aimed to reveal the extent of drug interactions between donafenib, lenvatinib and empagliflozin and henagliflozin in rats and explore the possible mechanisms.Rats were divided into fourteen groups (n = 6) that received empaglifiozin(1,2),henagliflozin(3,4,)donafenib(5), lenvatinib(6), empaglifiozin and donafenib (7), hennagliflozin and donafenib (8), empaglifiozin and lenvatinib(9) ,henagliflozin and lenvatinib (10),donafenib and empaglifiozin (11), donafenib and henagliflozin (12),lenvatinib and empaglifiozin(13),lenvatinib and henagliflozin(14). The concentrations of drugs were determined by an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. The messenger RNA (mRNA) expressions were measured by quantitative RT-PCR. Multiple administration of empagliflozin reduced the area under the concentration-time curve (AUC0 − t and AUC0−∞) of donafenib by 33.46% and 32.7% respectively. The apparent clearance rate (CLz/F) and apparent volume of distribution (Vd/F) were reduced by 66.7% and 95.2%, respectively. The half-life (T1/2) was prolonged by 17.6%.Henagliflozin modest decreased donafenib AUC0 − t and AUC0−∞ by 27.8% and 26.9%. The CLz/F of donafenib was 2.6-fold compared to the control group.Multiple doses of donafenib caused empagliflozin to AUC0 − t and AUC0−∞ increased by 57.5%and58.5%. CLz/F were significantly decreased by 39.9% .The combination of multiple doses of donafenib increased the maximum plasma concentration (Cmax) of henagliflozin by 65.5%, AUC0 − t and AUC0−∞ by 177.0% and178.0%, respectively. CLz/F and Vz/F of hanagliflozin were decreased by 64.1% and 45.1%.Multiple administration of empagliflozin decreased the AUC0 − t and AUC0−∞ of lenvatinib by 18.7% and21.4%, respectively. CLz/F was accelerated by 30.0%. After multiple administration of constant gliflozin, the AUC0 − t and AUC0−∞ of lenvatinib decreased by 20.3% and 20.9%, respectively, and CLz/F increased by 1.30-flod.Multiple doses of lenvatinib had no significant effect on the pharmacokinetics of empagliflozin and henagliflozin.The pharmacokinetic results suggest that it is important to take special care of the interactions of these drugs in clinical applications.

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“…7 Clinical data have shown that no dose adjustment is required when henagliflozin is combined with metformin, glimepiride, or valsartan. [8][9][10] A phase III trial showed that henagliflozin (5 and 10 mg) monotherapy effectively controlled blood glucose levels, reducing body weight and blood pressure. 11 The data for the marketed drug metformin showed that after oral administration of metformin hydrochloride tablets, blood concentration peaked after about 2.5 hours, with a terminal plasma clearance half-life of about 6.5 hours.…”

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confidence: 99%

Effects of Food and Multiple‐dose Administration on the Pharmacokinetic Properties of HR20033, a Sustained‐release Formulation of Henagliflozin and Metformin for the Treatment of Diabetes, in Healthy Chinese Volunteers

Liu

Huyan

Zhang

et al. 2022

Clinical Pharm in Drug Dev

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Henagliflozin proline and metformin hydrochloride sustained‐release tablets (HR20033) are a fixed‐dose combination of the novel, highly selective, and effective sodium‐glucose cotransporter‐2 inhibitor henagliflozin, with a metformin sustained‐release layer for the treatment of type 2 diabetes mellitus in conjunction with dietary control and exercise. The aims of this study were to investigate the effect of a high‐fat diet on the pharmacokinetics of henagliflozin and metformin after a single administration of HR20033 and the effect of repeated oral administration of HR20033 on their pharmacokinetics in healthy volunteers. The food‐effect clinical study involved 18 healthy subjects randomized to receive either HR20033 in the fasted condition followed by HR20033 in the fed condition or the reverse schedule, with the two doses separated by a washout period of at least 7 days. The multiple‐dose clinical study was conducted on 10 healthy subjects. In the food‐effect study, compared with those in the fasted condition, the area under the blood concentration curve (AUC) and peak concentration (Cmax) of henagliflozin decreased by 12.64% and 40.89%, respectively, while the AUC of metformin increased by 31.13% and Cmax decreased by 7.09% in the fed state. There was no significant accumulation of HR20033 in the body after multiple oral doses. No serious adverse event was observed in either of the two clinical studies. Food did not have a clinically meaningful effect on the absorption of HR20033.

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

Cited by 4 publications

References 21 publications

Risks and Benefits of SGLT-2 Inhibitors for Type 1 Diabetes Patients Using Automated Insulin Delivery Systems—A Literature Review

Risks and Benefits of SGLT-2 Inhibitors for Type 1 Diabetes Patients Using Automated Insulin Delivery Systems—A Literature Review

Pharmacokinetic interactions between donafenib and empagliflozin or henagliflozin , lenvatinib and empagliflozin or henagliflozin in rats

Effects of Food and Multiple‐dose Administration on the Pharmacokinetic Properties of HR20033, a Sustained‐release Formulation of Henagliflozin and Metformin for the Treatment of Diabetes, in Healthy Chinese Volunteers

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