Imeglimin: A New Promising and Effective Weapon in the Treatment of Type 2 Diabetes

Doupis, John; Baris, Neoklis; Avramidis, Konstantinos A.

doi:10.17925/ee.2021.17.2.88

Cited by 10 publications

(7 citation statements)

References 14 publications

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“…Imeglimin belongs to the class of dihydro-1, 3, 5-triazine derivatives. As a first-in-class treatment for type-2 diabetes (T2D), O n l i n e F i r s t imeglimin is a novel oral agent that is currently being studied T2D (Doupis et al, 2021). At the results of a number pivotal phase III trials, there were no reports of severe hypoglycemia, statistically significant glucose reductions, and favorable safety and tolerability profiles.…”

Section: Introductionmentioning

confidence: 99%

“…Imeglimin's mechanism of action consists of two effects: (a) increased insulin activity, which may have the ability to lower hepatic glucose output, and (b) increased insulin signaling in the liver and skeletal muscle. Imeglimin also maintains beta cell mass while increasing glucose-stimulated insulin secretion (Hallakou-Bozec et al, 2021). Based on literature survey, it was observed that there are some methods used for the estimation of imeglimin in biological matrices (Tomita et al, 2022), chiral resolution in crystallization method applying by magnetic substrates (Bhowmick et al, 2021), and methanol solvent (Wacharine-Antar et al, 2010) for imeglimin drug, but no analytical chiral method has been developed for the determination of imeglimin in its formulation.…”

Section: Introductionmentioning

confidence: 99%

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A sensitive direct chiral liquid chromatography tandem mass spectrometry method for the enantio—Selective analysis of imeglimin in formulation

Ramalingam¹,

Subramania²,

Basuvan³

et al. 2023

J Appl Pharm Sci

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The purpose of this study was to separate and develop a sensitive chiral liquid chromatography tandem mass spectrometry (LC-MS/MS) technique to estimate the (+) and (−) enantiomers of imeglimin in its formulation and validate individual enantiomer of the drug. Imeglimin is used to treat type-2 diabetes (T2D). The chiral stationary phase was reverse phase Chiralpak IG-3 (100 × 4.6 mm, 3 µm), whereas the isocratic mobile phase was methanol and 10 mM ammonium acetate (95:5 v/v ratio) and the flow rate was 0.5 ml/minutes. The resolution of the (+) and (−) enantiomers was monitored using LC-ESI-MS/MS in positive transition at 155.0 m/z (M+H) for imeglimin. The (+) and (−) linearity ranges from 10 to 100 ng/ml. The correlation co-efficient (R 2 ) of the (+) and (−) imeglimin enantiomers was found to be linear. The retention time of the (+) and (−) enantiomers of the drug was 2.876 and 4.325 minutes and the total run time of the chromatographic resolution was 5 minutes. As a result, our goal is to separate the enantiomers and develop a fast, sensitive, and cost-effective method for estimating (+) and (−) enantiomers in its formulation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A sensitive direct chiral liquid chromatography tandem mass spectrometry method for the enantio—Selective analysis of imeglimin in formulation

Ramalingam¹,

Subramania²,

Basuvan³

et al. 2023

J Appl Pharm Sci

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“…Dapagliflozin) [6]. Even after the availability of several anti-diabetic agents none of them targets all three components of diabetes pathophysiology such as excessive glucose production due gluconeogenesis, increased insulin resistance and lack of insulin production due to pancreatic β-cell dysfunction [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of Stability Indicating Rp-Uhplc Method for the Estimation of Imeglimin Hydrochloride Used for the Treatment of Metabolic Disorder Diabetes Mellitus

JAIN,

SONI,

SHARMA

2023

Int J App Pharm

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Objective: The present work was aimed to develop and validate a novel, simple, rapid, consistent, and sensitive stability indicating reverse phase ultra-high-performance liquid chromatographic (RP-UHPLC) method for the determination of oral anti-diabetic drug Imeglimin Hydrochloride in bulk and pharmaceuticals dosage form as per the technical recommendations of International Council for Harmonization guidelines for human use pharmaceutical (ICH-Q2(R1)). Methods: A novel simple, selective, stable and sensitive stability indicating method which used isocratic RP-UHPLC methodology for the quantitative measurement of Imeglimin Hydrochloride was developed. The chromatographic separation of Imeglimin Hydrochloride was achieved on RP-UHPLC equipped with Hypersil gold ODS endcapped column of dimensions (150x4.6 mm, 3micron) using isocratic elution with a mobile phase consisting of water: acetonitrile in a ratio of (15:85% v/v) at a flow rate of 1 ml/min with an injection volume of 20 µl. All measurements are done on 240 nm using eight channels Dionex Ultimate 3000 PDA detector equipped with chromeleon data acquisition system for data integration. Validation of the proposed method was carried out according to the (ICH-Q2 (R1)) guidelines. Results: The retention time of the Imeglimin Hydrochloride was found to be 3.831 with excellent absorbance sensitivity at 240 nm wavelength. The linear regression equation was found to be y = 3199x+1605.5 with a correlation coefficient (R2)>0.999 which shows excellent linear correlation. Specificity, linearity, precision, accuracy robustness, LOD and LOQ were determined for method validation and results were found to be well within recommended limits as per ICH guidelines. Conclusion: The proposed stability indicating reverse phase ultra-high-performance liquid chromatographic (RP-UHPLC) method was found to be fast, affordable, robust, precise and specific for estimation of Imeglimin Hydrochloride in pharmaceutical dosage form.

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“…The main target of imeglimin is correction of mitochondrial dysfunction by modulating respiratory chain complex activities while decreasing reactive oxygen species production [ 2 ]. Imeglimin has been shown to amplify glucose-stimulated insulin secretion by improving the β-cell glucose response and to ameliorate insulin sensitivity in T2D patients [ 3 ]. A clinical trial showed that imeglimin treatment for 7 days clearly increased glucose-stimulated insulin secretion during hyperglycemic clamps in T2D patients [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

The Effects of Imeglimin on the Daily Glycemic Profile Evaluated by Intermittently Scanned Continuous Glucose Monitoring: Retrospective, Single-Center, Observational Study

et al. 2022

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Introduction Imeglimin is a novel antidiabetic drug that amplifies glucose-stimulated insulin secretion (GSIS) and improves insulin sensitivity. Several randomized clinical studies have shown the efficacy of imeglimin for glycemic control in patients with type 2 diabetes (T2D). We aimed to evaluate the short-term effects and safety of imeglimin in terms of glycemic control, as assessed by intermittently scanned continuous glucose monitoring (isCGM). Methods This retrospective and observational study of 32 patients who were administered imeglimin in addition to existing treatment regimens was designed to evaluate glycemic profiles. The patients were monitored for more than 4 weeks, including the day of starting imeglimin. The changes in glycemic indices, including mean glucose level, coefficient of variation (CV), time in range (TIR) and time above range (TAR), before and after imeglimin administration were analyzed, and data on adverse effects were collected by interview. Results Imeglimin administration significantly improved the mean values of glucose (from 159.0 ± 27.5 mg/dL to 141.7 ± 22.1 mg/dL; p < 0.001), TIR (from 67.9 ± 17.0% to 79.5 ± 13.3%; p < 0.001) and TAR (from 29.4 ± 17.5% to 17.9 ± 13.7%; p < 0.001) and tended to improve CV (from 29.0 ± 6.1 to 27.4 ± 5.58; p = 0.058). The curves of 24-h mean glucose level for all 32 subjects were shifted downward from the baseline after imeglimin administration. The high mean glucose level, high TAR, low TIR, low body mass index and low C-peptide were related to the efficacy of imeglimin for glycemic control. The main adverse effects were gastrointestinal disorders, and the incidence of hypoglycemia was increased in cases receiving a combination of imeglimin plus insulin or a glinide agent. Conclusion Imeglimin clearly shifted the daily glucose profile into an appropriate range in Japanese T2D patients, indicating improvement of short-term glycemic control. Imeglimin is thought to be a promising therapeutic agent for T2D patients, especially those with a low insulin secretory capacity, which is a common phenotype in East-Asian subjects with glucose intolerance.

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Imeglimin: A New Promising and Effective Weapon in the Treatment of Type 2 Diabetes

Cited by 10 publications

References 14 publications

A sensitive direct chiral liquid chromatography tandem mass spectrometry method for the enantio—Selective analysis of imeglimin in formulation

A sensitive direct chiral liquid chromatography tandem mass spectrometry method for the enantio—Selective analysis of imeglimin in formulation

Development and Validation of Stability Indicating Rp-Uhplc Method for the Estimation of Imeglimin Hydrochloride Used for the Treatment of Metabolic Disorder Diabetes Mellitus

The Effects of Imeglimin on the Daily Glycemic Profile Evaluated by Intermittently Scanned Continuous Glucose Monitoring: Retrospective, Single-Center, Observational Study

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