Su1926 Long-Term Treatment With a Dipeptidyl Peptidase-4 Inhibitor, Sitagliptin, Suppresses Intestinal Tumors in Models of Diabetes and Obesity

2016 ◽  
Vol 150 (4) ◽  
pp. S591
Author(s):  
Kaori Fujiwara ◽  
Naoki Yorifuji ◽  
Sadaharu Nouda ◽  
Kazuki Kakimoto ◽  
Toshihiko Okada ◽  
...  
Keyword(s):  
Dipeptidyl Peptidase ◽  
Term Treatment ◽  
Intestinal Tumors ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
Long Term Treatment ◽  
Diabetes And Obesity

scholarly journals A Novel Dipeptidyl Peptidase-4 Inhibitor DA-1229 Ameliorates Tubulointerstitial Fibrosis in Cyclosporine Nephrotoxicity in Mice

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 251
Author(s):  
Hye Sook Min ◽  
Ji Eun Lee ◽  
Jung Yeon Ghee ◽  
Young Sun Kang ◽  
Jin Joo Cha ◽  
...  
Keyword(s):  
Renal Disease ◽  
Structural Changes ◽  
Immunosuppressive Agent ◽  
Term Treatment ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
Long Term Treatment ◽  
Cyclosporine Nephrotoxicity ◽  
Progression Of Renal Disease

Cyclosporine A (CyA) is an immunosuppressive agent that induces nephrotoxicity with long-term treatment. The roles of DPP-4 and its inhibitors in cyclosporine nephrotoxicity are not fully understood. Therefore, we investigated the effects of a novel DPP-4 inhibitor, DA-1229, on the progression of renal disease in an experimental cyclosporine nephrotoxicity model. Chronic cyclosporine nephrotoxicity was induced in six-week-old male ICR mice by subcutaneous injections of CyA at a dose of 30 mg/kg for four weeks. Animals were treated with DA-1229 at a dose of 300 mg/kg per day in food for four weeks. Although DPP-4 activity did not increase in the kidneys of mice with induced cyclosporine nephrotoxicity, DA-1229 treatment significantly suppressed DPP-4 activity in both plasma and renal tissues. DPP-4 inhibition by DA-1229 led to significantly decreased albuminuria and urinary excretion of 8-isoprosatane. DPP-4 inhibition also substantially suppressed pro-inflammatory effects, profibrotic molecules, and macrophage infiltration, and led to the improvement in renal structural changes. Our results suggest that DPP-4 inhibition by DA-1229 provides renoprotective effects in an animal model of cyclosporine nephrotoxicity via antioxidant, anti-inflammatory, and anti-fibrotic mechanisms. DPP-4 inhibition may be a useful new therapeutic approach for the management of progressive renal disease in cyclosporine nephrotoxicity.

Abstract 15107: Long-Term Treatment With Sitagliptin Provides Multiple Ultrasonic-Evaluated Antiatherosclerotic Effects Independent of Diabetic Improvement for Type-2 Diabetics

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Tatsuaki Murakami ◽  
Sumio Mizuno
Keyword(s):  
Intima Media Thickness ◽  
Term Treatment ◽  
Dipeptidyl Peptidase 4 ◽  
Type 2 Dm ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
Type 2 Diabetics ◽  
Long Term Treatment ◽  
High Resolution Ultrasonography

Introduction: Diabetes mellitus (DM) is thought to be highly involved in complex atherothrombogenic processes, but the long-term antiatherosclerotic therapies in patients with type-2 DM have not been established. Hypothesis: Therefore we assessed hypothesis long-term treatment sitagliptin, a dipeptidyl peptidase-4 inhibitor recently developed antidiabetic agent, chronically inhibits atherosclerotic progression in patients with type-2 DM. Methods: Thirty-two type-2 diabetic patients with stable coronary artery disease were randomized to group-S where they received sitagliptin (50mg/day), or to group-C where they received enhanced antidiabetic therapy without a dipeptidyl peptidase-4 inhibitor for 2 years. We quantified flow-mediated endothelium-dependent dilation of right brachial artery after 5 minutes forearm occlusion (BFMD), and intima-media thickness of brachial artery (BIMT) using high-resolution ultrasonography. We also quantified intima-media thickness of common carotid artery (CIMT) using high-resolution ultrasonography. Changes in BFMD, BIMT, and CIMT were compared between the two study groups. Results: Group-S (n=16) manifested good compliance to the long-term treatment and improvements in diabetic and lipid variables represented by HbA1c and LDL after long-term medication of sitagliptin, while there were no improvements in group-C. BFMD (%) improved after medication in group-S (from 3.9±1.8 to 6.4±2.6, p<0.01) and BIMT (mm) decreased in group-SG (from 0.35±0.10 to 0.32±0.11, p=0.03), while both remained unchanged in group-C (BFMD; from 4.1±2.0 to 4.1±1.9, p=0.88, BIMT; from 0.34±0.13 to 0.35±0.12, p=0.54). CIMT (mm) did not increase in group-S (from 1.10±0.35 to 1.08±0.39, p=0.16) but increased in group-C (from 1.09±0.46mm to 1.16±0.47mm, p<0.01). Changes of BFMD or BIMT in group-S did not correlate to those of HbA1c (BFMD: r=0.17, p=0.79, BIMT: r=0.11, p=0.85). Conclusions: This study suggests that long-term treatment of sitagliptin safely improves arterial function and inhibits progression of wall thickness independent of reversal for diabetic status, which may have beneficial potentials for long-term management of atherosclerosis in type-2 diabetics.

scholarly journals Combination of Linagliptin and Metformin for the Treatment of Patients with Type 2 Diabetes

2015 ◽  
Vol 8 ◽  
pp. CMED.S10360 ◽  
Author(s):  
Thomas Haak
Keyword(s):  
Type 2 Diabetes ◽  
The United States ◽  
Term Treatment ◽  
Dipeptidyl Peptidase 4 ◽  
Treatment Regimens ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
Long Term Treatment ◽  
Proven Efficacy ◽  
Single Pill

Type 2 diabetes mellitus (T2DM) is a progressive condition requiring long-term treatment. Most patients with T2DM are unable to maintain normoglycemia using metformin alone; thus, combination therapy is a pivotal part of disease management. Addition of the dipeptidyl peptidase-4 inhibitor linagliptin, with its proven efficacy, low propensity for hypoglycemia, and weight neutrality, has been shown to improve glycemic control for patients who are not well controlled with metformin. As patients often have other comorbidities requiring pharmacotherapy, an increase in pill number, different prescribing frequencies, and timing of medications may adversely impact patients' adherence. Studies have shown that treatment nonadherence contributes to increased morbidity, mortality, and healthcare cost. In the United States, the single-pill combination (SPC) of linagliptin/metformin is available |in three strengths approved for twice-daily administration: 2.5/500 mg, 2.5/850 mg, and 2.5/1000 mg. The SPC has the potential to reduce pill burden and simplify patients' treatment regimens, thereby promoting improved adherence and efficacy.

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