Possibility of pharmacokinetic drug interaction between a DPP-4 inhibitor and a SGLT2 inhibitor

Gu, Namyi; Park, Sang‐In; Chung, Hyewon; Jin, Xuanyou; Lee, Seung Hwan; Kim, Tae Eun

doi:10.12793/tcp.2020.28.e4

Cited by 18 publications

(26 citation statements)

References 63 publications

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“…The combination treatment using dapagliflozin and linagliptin is reasonable considering their complementary effects due to the different mechanisms of action, different metabolism, and relatively fewer adverse events, including hypoglycemia [ 14 , 25 , 26 ]. Although dapagliflozin and linagliptin are substrates of P-gp transporter, several clinical studies have already demonstrated that a combination of SGLT-2 inhibitors and DPP-4 inhibitors did not show any significant drug–drug interactions (DDI) [ 17 , 27 , 28 ]. Assuming that linagliptin and dapagliflozin have similar chemical structures, the possibility of DDI via P-gp may not be significant.…”

Section: Discussionmentioning

confidence: 99%

“…The combined use of dapagliflozin and linagliptin for managing T2DM is reasonable and attractive because of their different but complementary mechanisms of action and separate paths of degradation (i.e., metabolism), thereby avoiding possible drug interactions, which is important for harnessing drug pharmacodynamics and reducing the risk of unexpected adverse events [ 14 , 15 , 16 , 17 ]. Compared with a DPP-4 inhibitor, the combined use of SGLT-2 inhibitor and DPP-4 inhibitor is significantly associated with a decrease in glycemic control, body weight, and systolic blood pressure, and their advantages have already been proven for both initial combination and stepwise approaches [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of a Fixed-Dose Combination Product of Dapagliflozin and Linagliptin and Its Comparison with Co-Administration of Individual Tablets in Healthy Humans

et al. 2022

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Dapagliflozin, a selective sodium–glucose co-transporter-2 inhibitor, and linagliptin, a competitive, reversible dipeptidyl peptidase-4 inhibitor, are commonly prescribed antidiabetic medications in general clinics. Since there are several merits to combining them in a fixed-dose combination product, this study investigated the pharmacokinetic equivalence between the individual component (IC) and fixed-combination drug product (FCDP) forms of dapagliflozin and linagliptin. A randomized, open-label, single-dose crossover study was conducted. All participants (n = 48) were randomly allocated to group A (period 1: ICs, period 2: FCDP) or group B (period 1: FCDP, period 2: ICs), and each group received either a single dose of IN-C009 (FCDP) or single doses of both dapagliflozin and linagliptin. There was no statistically significant difference found between the pharmacokinetic variables of FCDP and IC. The values of estimated geometric mean ratios and the 90% confidence interval for both maximum concentration and area under the plasma drug concentration–time curve were within the range of 0.8–1.25 for both dapagliflozin and linagliptin. The results of the clinical study demonstrated comparable pharmacokinetic characteristics between IC and FCDP forms of dapagliflozin and linagliptin. The combined use of dapagliflozin and linagliptin was safe and tolerable in both formulations.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of a Fixed-Dose Combination Product of Dapagliflozin and Linagliptin and Its Comparison with Co-Administration of Individual Tablets in Healthy Humans

et al. 2022

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“…The excretion rate of unmetabolized tofogliflozin was 18.1%, whereas that of ipragliflozin was only 1%. The half-life of tofogliflozin is 5.4 h, whereas that of ipragliflozin is 15 h [ 38 – 40 ]. In the blood, these drugs are bound to plasma proteins such as albumin.…”

Section: Discussionmentioning

confidence: 99%

“…This discrepancy can be attributed to the difference between these two drugs in terms of half-life. The half-life of tofogliflozin is 5.4 h, whereas that of ipragliflozin is 15–16 h [ 38 – 40 ]. Therefore, when tofogliflozin is administered in the morning, it induces a stronger diurnal UGE effect than ipragliflozin, and this response decreases at night.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Tofogliflozin and Ipragliflozin for Patients with Type-2 Diabetes: A Randomized Crossover Study by Flash Glucose Monitoring

2020

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Introduction: Sodium-glucose cotransporter 2 (SGLT2) inhibitors promote urinary glucose excretion. However, the differences in the effects of various SGLT2 inhibitors are unknown. We used flash glucose monitoring (FGM) to identify the differences between tofogliflozin and ipragliflozin in terms of efficacy in reducing glycemic variability and mitigate hypoglycemia risk. Methods: In this crossover study, 24 patients with type-2 diabetes mellitus (T2DM) receiving insulin glargine U300 therapy were randomly allocated to tofogliflozin and ipragliflozin or ipragliflozin and tofogliflozin group. Glycemic variability and hypoglycemia were compared using to the 3-day FGM data per treatment period. Results: Glucose level 2 h after each meal was significantly lower with tofogliflozin administration than with ipragliflozin administration. Time below the target glucose range after tofogliflozin administration was significantly lower than that after ipragliflozin administration (2.1% ± 4.4% vs. 8.7% ± 11.7%). The 24-h standard deviation of glucose level, mean amplitude of glycemic excursion, and mean percent time with nocturnal hypoglycemia after tofogliflozin administration were significantly lower than those after ipragliflozin administration. Conclusions: Tofogliflozin was more effective and safer than ipragliflozin in reducing glycemic variability and mitigating hypoglycemia risk in patients with T2DM treated with insulin glargine U300.

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“…3 After a single oral administration, linagliptin reaches the maximum plasma concentration (C max ) after approximately 1.5 h and has an elimination half-life of < 24 h and < 30% bioavailability. 4 Metformin, called 'Glucophage ® XR' (RLD), is a drug that improves blood sugar regulation in adult type 2 diabetics. 5 In the case of medical treatment, a minimum effective dose should be administered for this drug which is similar to sulfonylurea and insulin.…”

Section: Introductionmentioning

confidence: 99%

Design of Experiments for Critical Material Attributes Assessment of Linagliptin and Metformin Fixed-dose Combination Tablets

Kim¹

2021

IJPER

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Aim of work:This study aimed to determine the amount of excipients in the critical material attributes of linagliptin and metformin sustained release (SR) fixed-dose combination (FDC) tablets using design of experiments (DoE). Methods: A 2 3 full factorial design with three center points was performed. For the screening of excipients, 3-factor responses (mannitol, sodium starch glycolate and pregelatinized starch for linagliptin; hydroxypropyl methylcellulose, sodium carboxymethyl cellulose (CMC) and hydroxypropyl cellulose for metformin), 2-levels and 1-center (n=3) point with three responses (friability, assay and dissolution) were applied to the DoE batch using Design-Expert. Results: Most excipients were an important factor in the friability, assay and dissolution results (P<0.05). In the screening of excipients, mannitol (40-60 mg) and pregelatinized starch (40-60 mg) with sodium starch glycolate (5 mg) for linagliptin and hydroxypropyl cellulose (15-23 mg) and CMC (40-55 mg) with hydroxypropyl methylcellulose (260 mg) for metformin were optimal. Conclusion: In summary, selection for the amount of excipients can be defined through levels of risk based on three responses. It can be concluded that the ranges of excipients leading to high quality (low friability and optimal ranges of assay and dissolution) for the screening of excipients were successfully observed by the DoE approach.

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Possibility of pharmacokinetic drug interaction between a DPP-4 inhibitor and a SGLT2 inhibitor

Cited by 18 publications

References 63 publications

Pharmacokinetics of a Fixed-Dose Combination Product of Dapagliflozin and Linagliptin and Its Comparison with Co-Administration of Individual Tablets in Healthy Humans

Pharmacokinetics of a Fixed-Dose Combination Product of Dapagliflozin and Linagliptin and Its Comparison with Co-Administration of Individual Tablets in Healthy Humans

Efficacy and Safety of Tofogliflozin and Ipragliflozin for Patients with Type-2 Diabetes: A Randomized Crossover Study by Flash Glucose Monitoring

Design of Experiments for Critical Material Attributes Assessment of Linagliptin and Metformin Fixed-dose Combination Tablets

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