Fimasartan increases glucose‐stimulated insulin secretion in patients with type 2 diabetes and hypertension compared with amlodipine

Yang, Ye; Lim, Min Hyuk; Lee, Seong Ok; Roh, Eun; Ahn, Chang Ho; Kwak, Soo Heon; Cho, Young Min; Kim, Sungwan; Mari, Andrea; Park, Kyong Soo; Jung, Hye Seung

doi:10.1111/dom.13282

Cited by 6 publications

(4 citation statements)

References 35 publications

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“…Although a recent clinical study reported an effect of increased insulin secretion for fimasartan in type 2 diabetic patients, 23 relatively few studies have described the effects or mechanism of fimasartan-mediated improvements in glucose metabolism.…”

Section: Discussionmentioning

confidence: 99%

Fimasartan Ameliorates Deteriorations in Glucose Metabolism in a High Glucose State by Regulating Skeletal Muscle and Liver Cells

et al. 2022

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Purpose Since diabetes and hypertension frequently occur together, it is thought that these conditions may have a common pathogenesis. This study was designed to evaluate the anti-diabetic function of the anti-hypertensive drug fimasartan on C2C12 mouse skeletal muscle and HepG2 human liver cells in a high glucose state. Materials and Methods The anti-diabetic effects and mechanism of fimasartan were identified using Western blot, glucose uptake tests, oxygen consumption rate (OCR) analysis, adenosine 5′-triphosphate (ATP) enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining for diabetic biomarkers in C2C12 cells. Protein biomarkers for glycogenolysis and glycogenesis were evaluated by Western blotting and ELISA in HepG2 cells. Results The protein levels of phosphorylated 5′ adenosine monophosphate-activated protein kinase (p-AMPK), p-AKT, insulin receptor substrate-1 (IRS-1), and glucose transporter type 4 (Glut4) were elevated in C2C12 cells treated with fimasartan. These increases were reversed by peroxisome proliferator-activated receptor delta (PPARδ) antagonist. ATP, OCR, and glucose uptake were increased in cells treated with 200 µM fimasartan. Protein levels of glycogen phosphorylase, glucose synthase, phosphorylated glycogen synthase, and glycogen synthase kinase-3 (GSK-3) were decreased in HepG2 cells treated with fimasartan. However, these effects were reversed following the addition of the PPARδ antagonist GSK0660. Conclusion In conclusion, fimasartan ameliorates deteriorations in glucose metabolism as a result of a high glucose state by regulating PPARδ in skeletal muscle and liver cells.

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Section: Discussionmentioning

confidence: 99%

Fimasartan Ameliorates Deteriorations in Glucose Metabolism in a High Glucose State by Regulating Skeletal Muscle and Liver Cells

et al. 2022

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“…An open‐label, active comparator‐controlled, crossover study also demonstrated that when compared with other antihypertensive agents, ARBs treatment are more beneficial in subjects with T2DM through increasing late‐phase glucose‐stimulated insulin secretion . 30 To the best of our knowledge, few studies examined the relationship between ARBs treatment and insulin secretion in patients with T2DM, though some studies were conducted in patients with prediabetes 31 . Preserving β ‐cell function is vital to patients with T2DM.…”

Section: Discussionmentioning

confidence: 99%

Annual decline in β‐cell function in patients with type 2 diabetes in China

Gao

Yan

Fang

et al. 2020

Diabetes Metabolism Res

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Background The aim of this study was to investigate the annual decline of β‐cell function correlated with disease duration in patients with type 2 diabetes in China. Methods This cross‐sectional study included 4792 adults with type 2 diabetes who were recruited from four university hospital diabetes clinics between April 2018 and November 2018. Baseline data were collected from electric medical records. Participants were divided into 21 groups with 1‐year diabetes duration interval to assess the decline rate of β‐cell function. Homeostatic model assessment model (HOMA 2) model was applied to assess β‐cell function. Multiple linear regression model was used to evaluate the association between biochemical and clinical variables and β‐cell function. Results In Chinese patients with type 2 diabetes, β‐cell function declined by 2% annually. Using angiotensin receptor blockade (ARB) (β = .048; P = .011), metformin (β = .138; P = .021), or insulin (β = .142; P = .018) was associated with increased β‐cell function. However, increased BMI (β = −.215; P = .022), alcohol consumption (β = −.331; P < .001), haemoglobin A1c (β = −.104; P = .027), or increased diabetes duration (β = −.183; P = .003) was significantly and negatively associated with β‐cell function. Conclusions We determined that the annual rate of the β‐cell function decline was 2% in patients with type 2 diabetes in China. Moreover, we confirmed a positive relationship between ARB treatment and β‐cell function, while BMI and alcohol consumption were significantly and negatively associated with the β‐cell function.

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“…14 According to the report by Yang et al, insulin secretion is increased by fimasartan treatment in patients with type 2 diabetes and hypertension, compared with amlodipine. 15 These findings suggest that fimasartan combined with linagliptin would be more beneficial in such patients. However, to our knowledge, there are no reports of studies on the interaction between fimasartan and linagliptin.…”

Section: Introductionmentioning

confidence: 95%

<p>A Pharmacokinetic Drug Interaction Between Fimasartan and Linagliptin in Healthy Volunteers</p>

Kang

Lee

Gwon

et al. 2020

DDDT

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Objective: Fimasartan, an angiotensin II type 1 receptor blocker, and linagliptin, a dipeptidyl-peptidase-4 inhibitor, are frequently coadministered to treat patients with hypertension and diabetes, respectively. This study sought to evaluate the pharmacokinetic interactions between fimasartan and linagliptin after co-administration in healthy Korean subjects. Methods: The overall study was divided into two separate parts, with each part designed as an open-label, multiple-dose, two-period, and single-sequence study. In Part A, to investigate the effect of linagliptin on fimasartan, 25 subjects received 120 mg fimasartan alone once daily for seven days during Period I, and 120 mg fimasartan with 20 mg linagliptin for seven days during Period II. In Part B, to examine the effect of fimasartan on linagliptin, 12 subjects received only linagliptin once daily for seven days during Period I, followed by concomitant administration of fimasartan for seven days during Period II, at the same doses used in Part A. Serial blood samples were collected at scheduled intervals for up to 24 h after the last dose to determine the steady-state pharmacokinetics of both drugs. Results: Thirty-six subjects completed the study. The geometric mean ratio and 90% confidence intervals for maximum plasma concentration at steady state (C max,ss ) and area under the concentration-time curve at steady state (AUC τ,ss ) of fimasartan with or without linagliptin were 1.2633 (0.9175-1.7396) and 1.1740 (1.0499-1.3126), respectively. The corresponding values for C max,ss and AUC τ,ss of linagliptin with or without fimasartan were 0.9804 (0.8480-1.1336) and 0.9950 (0.9322-1.0619), respectively. A total of eight adverse events (AEs) were reported and the incidence of AEs did not increase significantly with co-administration of the drugs. Conclusion: Our results suggest that there are no clinically significant pharmacokinetic interactions between fimasartan and linagliptin when co-administered. Treatments were well tolerated during the study, with no serious adverse effects.

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Fimasartan increases glucose‐stimulated insulin secretion in patients with type 2 diabetes and hypertension compared with amlodipine

Abstract: Compared with amlodipine, fimasartan increased late-phase glucose-stimulated insulin secretion in patients with type 2 diabetes and hypertension. This finding suggests that ARBs would be more beneficial in such patients compared with other classes of anti-hypertensives.

Cited by 6 publications

References 35 publications

Fimasartan Ameliorates Deteriorations in Glucose Metabolism in a High Glucose State by Regulating Skeletal Muscle and Liver Cells

Fimasartan Ameliorates Deteriorations in Glucose Metabolism in a High Glucose State by Regulating Skeletal Muscle and Liver Cells

Annual decline in β‐cell function in patients with type 2 diabetes in China

<p>A Pharmacokinetic Drug Interaction Between Fimasartan and Linagliptin in Healthy Volunteers</p>

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