Efficacy and safety of saxagliptin, a dipeptidyl peptidase-4 inhibitor, in hemodialysis patients with diabetic nephropathy: A randomized open-label prospective trial.
OBJECTIVE
Saxagliptin is a dipeptidyl peptidase-4 inhibitor that was approved in Japan for the treatment of type 2 diabetes in 2013. We examined its efficacy and safety in Japanese hemodialysis patients with diabetic nephropathy.


METHODS
In this prospective, open-label, parallel-group study, Japanese hemodialysis patients were randomized to receive either oral saxagliptin (2.5mg/day) or usual care (control group) for 24weeks. Before randomization, patients received fixed doses of conventional antidiabetic drugs (oral drugs and/or insulin) for 8weeks; these drugs were continued during the study. Endpoints included changes in glycated albumin (GA), hemoglobin A1c (HbA1c), postprandial plasma glucose (PPG), and adverse events.


RESULTS
Both groups included 41 patients. Mean GA, HbA1c, and PPG decreased significantly in the saxagliptin group (-3.4%, -0.6% [-7mmol/mol], and -38.3mg/dL, respectively; all P<0.0001) but not in the control group (0%, -0.1% [-1mmol/mol], and -3.7mg/dL, respectively) (P<0.0001, P<0.001, and P<0.0001, respectively). In saxagliptin-treated patients, the reduction in GA was significantly greater when saxagliptin was administered as monotherapy than in combination therapy (-4.2% vs. -3.0%, P=0.012) despite similar baseline values (24.5% vs. 23.3%). Reductions in GA, HbA1c, and PPG were greater in patients whose baseline values exceeded the median (23.8% for GA, 6.6% for HbA1c, and 180mg/dL for PPG). There were no adverse events associated with saxagliptin.


CONCLUSIONS
Saxagliptin (2.5mg/day) was effective and well tolerated when used as monotherapy or combined with other antidiabetic drugs in Japanese hemodialysis patients with type 2 diabetes.


BACKGROUND
UMIN000018445.
Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. Electronic address: abe.masanori@nihon-u.ac.jp.
Masanori
M
Abe
Department of Nephrology, Keiai Hospital, Tokyo, Japan. Electronic address: thiguchi@keiai-hospital.jp.
Terumi
T
Higuchi
Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. Electronic address: mi.piace.hayden.v@gmail.com.
Masari
M
Moriuchi
Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. Electronic address: patrickemboma@yahoo.co.jp.
Masahiro
M
Okamura
Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. Electronic address: haru_li_huang@yahoo.co.jp.
Ritsukou
R
Tei
Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. Electronic address: nagura.chinami@nihon-u.ac.jp.
Chinami
C
Nagura
Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. Electronic address: craftsmanship.t.h@gmail.com.
Hiroyuki
H
Takashima
Department of Nephrology, Meirikai Chuo General Hospital, Tokyo, Japan. Electronic address: kikuchi5308@air.ocn.ne.jp.
Fumito
F
Kikuchi
Department of Nephrology, Yujin Clinic, Tokyo, Japan. Electronic address: yjntomita@gmail.com.
Hyoe
H
Tomita
Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan. Electronic address: okada.kazuyoshi@nihon-u.ac.jp.
Kazuyoshi
K
Okada
D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004151:Dipeptides / Q000009:adverse effects / Q000627:therapeutic use*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D017127:Glycation End Products, Advanced; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D006435:Renal Dialysis; D012709:Serum Albumin / Q000187:drug effects / Q000378:metabolism; D000093423:Glycated Serum Albumin
D000218:Adamantane; D001786:Blood Glucose; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D012709:Serum Albumin; D000093423:Glycated Serum Albumin; C502994:saxagliptin
Glycated albumin; Hemodialysis; Saxagliptin; Type 2 diabetes