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      Comparative effect of dipeptidyl-peptidase 4 inhibitors on laboratory parameters in patients with diabetes mellitus

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          Abstract

          Background

          The purpose of this study was to evaluate and compare the effects on laboratory parameters among monotherapy with five DPP-4 inhibitors in patients with type 2 diabetes mellitus (DM).

          Methods

          We identified cohorts of new sitagliptin users ( n = 879), vildagliptin users ( n = 253), teneligliptin users ( n = 260), alogliptin users ( n = 237), and linagliptin users ( n = 180) in patients with type 2 DM. We used a multivariate regression model to evaluate and compare the effects of the drugs on laboratory parameters including HbA1c concentration and serum concentrations of creatinine, estimated glomerular filtration rate, high density lipoprotein, total cholesterol, triglyceride, aspartate aminotransferase, and alanine aminotransferase among the five DPP-4 inhibitors up to 12 months.

          Results

          Our study showed a favorable effect on HbA1c concentration and a slightly unfavorable effect on serum creatinine concentration in users of the five DPP-4 inhibitors, a favorable effect on lipid metabolism in sitagliptin, vildagliptin, and alogliptin users, and a favorable effect on hepatic parameters in sitagliptin, alogliptin, and linagliptin users, in comparison of the baseline and exposure periods. However, there was no significant difference in mean change in the concentration of any laboratory parameter among the five groups of DPP-4 inhibitor users.

          Conclusions

          In this study, we showed the effect of five DPP-4 inhibitors on glycemic, renal, and lipid metabolism, and hepatic parameters. DPP-4 inhibitors are well-tolerated hypoglycemic drugs.

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          Most cited references21

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          K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease.

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            Glucagon-like peptide 1 induces natriuresis in healthy subjects and in insulin-resistant obese men.

            Glucagon-like peptide-1-(7-36)-amide (GLP-1) is involved in satiety control and glucose homeostasis. Animal studies suggest a physiological role for GLP-1 in water and salt homeostasis. This study's aim was to define the effects of GLP-1 on water and sodium excretion in both healthy and obese men. Fifteen healthy subjects and 16 obese men (mean body mass index, 36 kg/m2) were examined in a double-blind, placebo-controlled, crossover study to demonstrate the effects of a 3-h infusion of GLP-1 on urinary sodium excretion, urinary output, and the glomerular filtration rate after an i.v. 9.9-g salt load. Infusion of GLP-1 evoked a dose-dependent increase in urinary sodium excretion in healthy subjects (from 74 +/- 8 to 143 +/- 18 mmol/180 min, P = 0.0013). In obese men, there was a significant increase in urinary sodium excretion (from 59 to 96 mmol/180 min, P = 0.015), a decrease in urinary H+ secretion (from 1.1 to 0.3 pmol/180 min, P = 0.013), and a 6% decrease in the glomerular filtration rate (from 151 +/- 8 to 142 +/- 8 ml/min, P = 0.022). Intravenous infusions of GLP-1 enhance sodium excretion, reduce H+ secretion, and reduce glomerular hyperfiltration in obese men. These findings suggest an action at the proximal renal tubule and a potential renoprotective effect.
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              Dose-ranging efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes mellitus.

              Sitagliptin is an oral, potent, highly selective, once-daily DPP-4 inhibitor indicated for the treatment of type 2 diabetes mellitus (T2DM). To assess the dose-ranging efficacy and safety/tolerability profile of once-daily sitagliptin 25, 50, 100, and 200 mg in Japanese patients with T2DM. In this randomized, double-blind, placebo-controlled study, 363 Japanese patients with inadequate glycemic control (HbA(1c)=6.5-10%; FPG or =50 mg, differences in HbA(1c), FPG, and 2-hr PPG between the sitagliptin groups were not statistically significant. Sitagliptin was generally well tolerated with a low and similar incidence of hypoglycemia and minimal weight gain relative to placebo. Treatment with sitagliptin for 12 weeks provided significant and clinically meaningful reductions in HbA(1c), FPG, and 2-hr PPG across the dose range studied and was generally well tolerated in Japanese patients with T2DM.
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                Author and article information

                Contributors
                nishida.yayoi@nihon-u.ac.jp
                takahashi.yasuo@nihon-u.ac.jp
                teduka.kotoe@nihon-u.ac.jp
                akimoto.hayato@nihon-u.ac.jp
                nakayama.tomohiro@nihon-u.ac.jp
                asai.satoshi@nihon-u.ac.jp
                Journal
                BMC Pharmacol Toxicol
                BMC Pharmacol Toxicol
                BMC Pharmacology & Toxicology
                BioMed Central (London )
                2050-6511
                21 April 2020
                21 April 2020
                2020
                : 21
                : 28
                Affiliations
                [1 ]GRID grid.260969.2, ISNI 0000 0001 2149 8846, Division of Pharmacology, Department of Biomedical Sciences, , Nihon University School of Medicine, ; 30-1 Oyaguchi-Kamimachi, Itabashi-ku, Tokyo, 173-8610 Japan
                [2 ]GRID grid.260969.2, ISNI 0000 0001 2149 8846, Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, , Nihon University School of Medicine, ; 30-1 Oyaguchi-Kamimachi, Itabashi-ku, Tokyo, 173-8610 Japan
                [3 ]GRID grid.260969.2, ISNI 0000 0001 2149 8846, Division of Laboratory Medicine, Department of Pathology and Microbiology, , Nihon University School of Medicine, ; 30-1 Oyaguchi-Kamimachi, Itabashi-ku, Tokyo, 173-8610 Japan
                Article
                407
                10.1186/s40360-020-00407-4
                7171729
                32317005
                c9fb493e-b45f-4adb-af09-24e1e735a5b1
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 5 September 2019
                : 27 March 2020
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Toxicology
                diabetes mellitus,dipeptidyl-peptidase 4 inhibitor,sitagliptin,vildagliptin,teneligliptin,alogliptin,linagliptin

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