Regulation of Free Fatty Acid by Sitagliptin Monotherapy in DRUG-NAÏVE Subjects with Type 2 Diabetes

Kutoh, Eiji; Wada, Asuka; Hayashi, Jyunka

doi:10.4158/ep-2018-0287

Cited by 9 publications

(12 citation statements)

References 31 publications

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“…Measurements of HbA1c and FBG were performed once a month. TC, TG, HDL‐C, non‐HDL‐C, LDL‐C and insulin were measured using standard techniques 9,10 at the start (baseline) and at the end (3 months) of the study. FFA concentrations were determined by colorimetry with enzymatic reactions as described previously (Mitsubishi LSI or BML) 10 .…”

Section: Methodsmentioning

confidence: 99%

“…Inclusion criteria: the subjects were either newly diagnosed T2DM or were previously diagnosed but untreated. The diagnosis of T2DM was made according to the criteria of The Japan Diabetes Society as previously described 9,10 . The subjects did not receive any regularly prescribed drugs in the past 6 months prior to the study.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, this was an observational study including two prospective, non‐randomized groups. The subjects were encouraged to follow exercise and diet regimens as previously described 9,10 . Informed consent was obtained from the patients, and the study protocol was approved by the Ethics Committee/Institutional Review Board of Gyoda General Hospital.…”

Section: Methodsmentioning

confidence: 99%

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Complementary effects on glycaemic and non‐glycaemic parameters between responders and non‐responders treated with pioglitazone and canagliflozin in drug‐naive subjects with type 2 diabetes

Kutoh¹,

Kuto²,

Wada³

et al. 2021

Int J Clinical Practice

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Objectives The aim of this study was to investigate the differential regulation of metabolic parameters between pioglitazone and canagliflozin in relation to their glycaemic efficacies. Methods Drug‐naive subjects with T2DM received pioglitazone 15‐30 mg/day or canagliflozin 50‐100 mg/day monotherapy for 3 months. Those who had a ≥1% reduction in HbA1c were defined as responders and others who had a <1% reduction were defined as non‐responders. Results In the pioglitazone group, baseline BMI, FFA, HOMA‐R or adipo‐IR was significantly higher, and HDL‐C was significantly lower in responders vs non‐responders. In the canagliflozin group, baseline HbA1c or FBG was significantly higher, and HOMA‐B or age was significantly lower in responders vs non‐responders. In pioglitazone responders, significant decreases in HbA1c (from 10.75% to 8.31%), FBG (−29.7%), FFA (−37.7%), non‐HDL‐C (−13.4%), TG (−30.1%), HOMA‐R (−35.6%) or adipo‐IR (−38.7%), and increases in BMI (2.8%) or HDL‐C (14.2%) were observed. In pioglitazone non‐responders, none of the parameters were regulated. In canagliflozin responders, significant decreases in HbA1c (from 11.31% to 8.60%), FBG (32.1%), BMI (−2%) or HOMA‐R (−33.8%), and increases in HOMA‐B (50%) were observed. In canagliflozin non‐responders, significant decreases in BMI (−2.4%), insulin (−21.8%) or HOMA‐R (−33.6%) were observed. Conclusions (i) Glycaemic efficacy of pioglitazone is linked to body weight and atherogenic lipids while this is not the case with canagliflozin. (ii) Responders (or non‐responders) to pioglitazone have some distinct features from non‐responders (or responders) to canagliflozin. Collectively, a combination of pioglitazone and canagliflozin may compensate for each other's metabolic drawbacks or augment their advantages, thereby achieving overall improvements in the metabolic profiles and pathogenic defects of patients with T2DM.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Complementary effects on glycaemic and non‐glycaemic parameters between responders and non‐responders treated with pioglitazone and canagliflozin in drug‐naive subjects with type 2 diabetes

Kutoh¹,

Kuto²,

Wada³

et al. 2021

Int J Clinical Practice

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“…The LDL-C-lowering effect of anagliptin at 24 weeks was comparable to that of alogliptin, although the anagliptin-mediated reduction in LDL-C level was associated with suppression of apolipoprotein B-100 synthesis in patients with T2D [3]. On the other hand, sitagliptin is also known to decrease serum cholesterol levels in patients with T2D [17–19]. Masuda et al [18] found that 12 weeks of sitagliptin treatment improved lipid profiles accompanied by reductions in several atherogenic remnant lipoproteins.…”

Section: Discussionmentioning

confidence: 99%

“…Masuda et al [18] found that 12 weeks of sitagliptin treatment improved lipid profiles accompanied by reductions in several atherogenic remnant lipoproteins. Kutoh et al [19] also reported that sitagliptin down-regulated high free fatty acid (FFA) levels and reduced atherogenic cholesterol levels. Furthermore, in experimental T2D model rats sitagliptin ameliorated left ventricular diastolic dysfunction by shifting FFA towards glucose utilization in cardiomyocytes in conjunction with a reduction in lipolysis.…”

Section: Discussionmentioning

confidence: 99%

Differences in lipid metabolism between anagliptin and sitagliptin in patients with type 2 diabetes on statin therapy: a secondary analysis of the REASON trial

Chihara

Tanaka

Morimoto

et al. 2019

Cardiovasc Diabetol

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Background: Anagliptin, a dipeptidyl peptidase-4 inhibitor, is reported to reduce the level of low-density lipoprotein cholesterol (LDL-C). The underlying mechanism of this effect and effect on lipid metabolism however remains uncertain. Aim and methods:We therefore evaluate the effects of anagliptin on lipid metabolism-related markers compared with those of sitagliptin. The study was a secondary analysis using data obtained from the Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. This trial in patients with type 2 diabetes at a high risk of cardiovascular events and on statin therapy showed that anagliptin reduced LDL-C levels to a greater extent than sitagliptin. Cholesterol absorption (campesterol and sitosterol) and synthesis (lathosterol) markers were measured at baseline and 52 weeks in the study cohort (n = 353). Results:There was no significant difference in the changes of campesterol or sitosterol between the two treatment groups (p = 0.85 and 0.55, respectively). Lathosterol concentration was increased significantly at 52 weeks with sitagliptin treatment (baseline, 1.2 ± 0.7 μg/mL vs. 52 weeks, 1.4 ± 1.0 μg/mL, p = 0.02), whereas it did not change in the anagliptin group (baseline, 1.3 ± 0.8 μg/mL vs. 52 weeks, 1.3 ± 0.7 μg/mL, p = 0.99). The difference in absolute change between the two groups showed a borderline significance (p = 0.06). Conclusion:These findings suggest that anagliptin reduces LDL-C level by suppressing excess cholesterol synthesis, even in combination with statin therapy.Trial registration ClinicalTrials.gov number NCT02330406. https ://clini caltr ials.gov/ct2/show/NCT02 33040 6; registered January 5, 2015.

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Alogliptin: a DPP-4 inhibitor modulating adipose tissue insulin resistance and atherogenic lipid

Kutoh

Kuto²,

Akiyama³

et al. 2023

Eur J Clin Pharmacol

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Regulation of Free Fatty Acid by Sitagliptin Monotherapy in DRUG-NAÏVE Subjects with Type 2 Diabetes

Cited by 9 publications

References 31 publications

Complementary effects on glycaemic and non‐glycaemic parameters between responders and non‐responders treated with pioglitazone and canagliflozin in drug‐naive subjects with type 2 diabetes

Complementary effects on glycaemic and non‐glycaemic parameters between responders and non‐responders treated with pioglitazone and canagliflozin in drug‐naive subjects with type 2 diabetes

Differences in lipid metabolism between anagliptin and sitagliptin in patients with type 2 diabetes on statin therapy: a secondary analysis of the REASON trial

Alogliptin: a DPP-4 inhibitor modulating adipose tissue insulin resistance and atherogenic lipid

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