Diabetes therapies in hemodialysis patients: Dipeptidase-4 inhibitors

Table 1 Seven dipeptidase-4 inhibitors

Dose and pharmacokinetics	Sitagliptin	Vildagliptin	Alogliptin	Linagliptin	Teneligliptin	Anagliptin	Saxagliptin
Daily dose (mg)	25	50	6.25	5	20	100	2.5
Molecular weight (Da)	523.32	303.4	461.51	472.54	628.86	383.45	333.43
Bioavailability	87%	85%	100%	30%	Unknown	73.2%	Unknown
Protein binding	38.0%	9.3%	28.2%-38.4%	> 80%	77.6%-82.2%	37.1%-48.2%	Negligible
Cmax (vs healthy volunteer)	1.4 fold	1.4 fold	3.2 fold	1.5 fold	1.0 fold	1.4 fold	Unknown
AUC (vs healthy volunteer)	4.5 fold	2.0 fold	3.8 fold	1.5 fold	1.5 fold	3.2 fold	2.1 fold
t1/2 (h) (vs healthy volunteer)	2.2	2	Unknown	Unknown	1.0 fold	0.9 fold	Unknown
Dialyzability	13.50%	3.00%	7.20%	Unknown	15.60%	Unknown	4.00%

Cmax, AUC and t_1/2 were measured under different dose conditions. AUC: Area under the curve.

Table 2 Combinations of oral antidiabetic drugs with dipeptidase-4 inhibitors

Class	Action mechanism	Glucose target	Drug	Daily dose (mg)
Sulfonylurea	Increases insulin secretion	Fasting and postprandial	Glipizide	2.5-10
			Gliclazide	40-240
			Gliquidone	45-60
Meglitinide	Increases insulin secretion	Postprandial	Repaglinide	0.5-12
			Mitiglinide	7.5-15
Thiazolidinediones	Insulin sensitizer	Fasting and postprandial	Rosiglitazone	4-8
			Pioglitazone	15-45
Alpha-glucosidase inhibitor	Delays carbohydrate absorption	Postprandial	Voglibose	0.6-0.9
			Acarbose	75-300
			Miglitol	150-225

Table 3 Efficacies of dipeptidase-4 inhibitor monotherapies

Ref.	Studyduration (mo)	n	DPP-4 inhibitor	Treatment dose (mg)	Parameter(%)	Pre-treatment	Post-treatment	Efficacy
Arjona Ferreira et al[9]	12	64	Sitagliptin	25	HbA1c	7.9	7.2	-0.7
					GA	Unknown	Unknown	Unknown
Ito et al[10]	6	5	Vildagliptin	50	HbA1c	6.0	5.5	-0.5
					GA	21.8	19.7	-2.1
Kume et al[11]	6	26	Vildagliptin	50	HbA1c	Unknown	Unknown	Unknown
					GA	23.8	21.2	-2.6
Ito et al[12]	6	9	Vildagliptin	50 or 100	HbA1c	6.7	6.0	-0.7
					GA	24.7	20.1	-4.6
Nakamura et al[13]	24	16	Alogliptin	6.25	HbA1c	7.1	5.8	-1.3
					GA	22.5	19.6	-2.9
Nakamura et al[14]	6	21	Linagliptin	5	HbA1c	Unknown	Unknown	Unknown
					GA	21.3	18.0	-2.3
Otsuki et al[15]	6	14	Teneligliptin	20	HbA1c	6.4	Unknown	-0.3 to -0.8
	7				GA	21.1	Unknown	-1.7 to -2.3

HbA1c: Hemoglobin A1c; GA: Glycated albumin.

Table 4 Efficacies of both monotherapies and combination therapies with dipeptidase-4 inhibitors

Ref.	Study duration (mo)	n	DPP-4 inhibitor	Treatment dose (mg)	Combination therapy	Parameter (%)	Pre-treatment	Post-treatment	Efficacy
Ito et al[12]	6	30	Vildagliptin	50 or 100	Mitiglinide and/or voglibose	HbA1c	6.7	6.1	-0.6
						GA	24.5	20.5	-4.0
Fujii et al[16]	12	30	Alogliptin	6.25	Mitiglinide and/or voglibose	HbA1c	7.2	6.3	-0.9
						GA	25.6	20.7	-4.9
Nowicki et al[17]	12	19	Saxagliptin	2.5	Unknown	HbA1c	8.7	7.5	-1.2
						GA	Unknown	Unknown	Unknown

HbA1c: Hemoglobin A1c; GA: Glycated albumin.