Anagliptin in the treatment of type 2 diabetes: safety, efficacy, and patient acceptability

Figures & data

Table 1 Pharmacological characteristics and use in the clinical setting in Japan and efficacy of DPP-4 inhibitors in patients with type 2 diabetes based on the data for Phase III clinical trials

	Sitagliptin	Vildagliptin	Alogliptin	Linagliptin	Teneligliptin	Saxagliptin	Anagliptin
IC50 (nmol/L)	17.9	9.7	10	1–3.6	0.9	1.3	3.3
T max (h)	2–5	1.3–2.8	1.0–1.4	6	1.0–1.8	0.8	0.9–1.8
T 1/2 (h)	9.6–12.3	1.5–5.3	14.3–21.8	97–105	2,124	6.0–6.8	5.8–6.2
Inhibition of plasma DPP-4 activity (%)	≥80	≥80	≥80	≥80	≥70	≥80	≥80
Increase in active GLP-1 levels	≥2-fold	1.8-fold	2-fold	Increase	≥2-fold	≥2-fold	≥2-fold
Dosing
Frequency	QD	BID	QD	QD	QD	QD	BID
Usual dose (daily)
Normal kidney function	50 mg	100 mg	25 mg	5 mg	20 mg	5 mg	200 mg
Ccr 30–50 mL/min	25 mg	50 mg	12.5 mg	5 mg	20 mg	2.5 mg	200 mg
Ccr <30 mL/min	12.5 mg	50 mg	6.25 mg	5 mg	20 mg	2.5 mg	100 mg
Efficacy as monotherapy
Study duration (weeks)	24	24	26	24	12	24	52
Baseline mean HbA1c (%)	8.01	8.4	7.9	8.0	7.8	7.9	8.22
Change in HbA1c (%)	−0.79*	−0.7	−0.59	−0.69	−0.8	−0.46	−0.63
Reference number	11	12	13	14	15	16	17

Notes: IC₅₀, T _max, T _1/2, the inhibition of plasma DPP-4 activity, and the increase in active GLP-1 levels were based on the drug information of the corresponding agent published by the pharmaceutical company.

* The dose of sitagliptin was 100 mg daily (QD).

Abbreviations: DPP-4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide-1; IC₅₀, half-maximal inhibitory concentration; T _max, maximum drug concentration time; T _1/2, half-life period; Ccr, creatinine clearance rate.

Figure 1 Prescription rates of antidiabetic agents.

Notes: The data were obtained from the database of Edogawa Hospital over three months. The prescription rate was calculated as the number of patients prescribed each class of antidiabetic agent divided by the total number of patients prescribed any type of antidiabetic agent. The number of patients prescribed α-glucosidase inhibitors, sulfonylureas, thiazolidinediones, and glinides has declined continuously since the release of dipeptidyl peptidase-4 (DPP-4) inhibitors. The rate of prescription of dipeptidyl peptidase-4 inhibitors increased steadily to more than 50% in 2013. In contrast, the use of insulin and biguanides has remained relatively stable at approximately 30%. Copyright ©2013. Journal of Japan Diabetes Society. Adapted from Ando S, Tsugami E, Suzuki S, et al. Recent trend in the prescription rates of antidiabetic agents in our facility. Journal of Japan Diabetes Society. 2013; 56 Suppl 1: S164.⁴⁵
Abbreviations: DPP-4, dipeptidyl peptidase-4; GLP-1, glucagon-like peptide-1.

Figure 2 Data for (A) patient age, (B) estimated glomerular filtration rate (eGFR), (C) urinary C-peptide, and (D) therapeutic methods for type 2 diabetes among the groups divided according to the duration of illness.

Notes: A population of 1,436 patients diagnosed with type 2 diabetes mellitus whose duration of illness was described in their medical records and who were treated for more than 6 months at the Department of Diabetes, Metabolism and Kidney Disease of Edogawa Hospital between 2008 and 2011 was examined. While the patient ages significantly increased in association with a longer duration of illness (P<0.0001, analysis of variance), both the estimated glomerular filtration rate (n=1436) and urinary C-peptide (n=424) values were significantly reduced (P<0.0001, analysis of variance). The proportion of patients receiving insulin treatment increased in association with a longer duration of illness (P<0.0001, χ² test). The data are shown as the means ± standard deviation. Filled, hatched, and open bars indicate insulin (including the combination of insulin and oral antidiabetic agents), oral antidiabetic agents, and nonpharmacological therapies, respectively.

Table 2 Changes in the levels of HbA_1c, fasting blood glucose, and postprandial blood glucose in the groups treated with combination therapy with anagliptin and other oral antidiabetic agents in a Phase III clinical trial

	Parameters	Treatment group	12 weeks (n)	52 weeks (n)
α-gucosidase inhibitors	HbA1c (%)	Placebo/anagliptin	0.12±0.58 (32)	−0.87±0.81 (94)###
		Anagliptin/anagliptin	−0.83±0.56 (62)***
	Fasting blood glucose (mg/dL)	Placebo/anagliptin	5.9±39.5 (32)	−15.6±29.3 (94)###
		Anagliptin/anagliptin	−18.5±25.7 (62)***
	Postprandial blood glucose (mg/dL)	Placebo/anagliptin	5.9±47.5 (32)	−38.5±48.9 (92)###
		Anagliptin/anagliptin	−43.1±38.3 (62)***
Biguanides	HbA1c (%)	Placebo/anagliptin	0.45±0.91 (36)	−0.67±1.15 (104)###
		Anagliptin/anagliptin	−0.62±0.67 (69)***
	Fasting blood glucose (mg/dL)	Placebo/anagliptin	10.9±35.2 (36)	−15.0±37.5 (104)###
		Anagliptin/anagliptin	−13.6±26.8 (69)***
	Postprandial blood glucose (mg/dL)	Placebo/anagliptin	15.6±43.5 (36)	−24.9±56.7 (100)###
		Anagliptin/anagliptin	−30.4±45.1 (67)***
Sulfonylureas	HbA1c (%)	Placebo/anagliptin	0.24±0.59 (45)	−0.36±0.84 (135)###
		Anagliptin/anagliptin	−0.53±0.48 (90)***
	Fasting blood glucose (mg/dL)	Placebo/anagliptin	2.0±27.8 (45)	−6.7±27.0 (135)##
		Anagliptin/anagliptin	−10.3±29.2 (90)*
	Postprandial blood glucose (mg/dL)	Placebo/anagliptin	1.9±40.6 (45)	−8.7±43.5 (134)#
		Anagliptin/anagliptin	−25.1±40.1 (90)***
Thiazolidinediones	HbA1c (%)	Placebo/anagliptin	0.32±0.67 (31)	−0.88±0.89 (102)###
		Anagliptin/anagliptin	−0.52±0.68 (71)***
	Fasting blood glucose (mg/dL)	Placebo/anagliptin	6.3±21.3 (31)	−19.8±26.9 (102)###
		Anagliptin/anagliptin	−15.9±34.9 (71)**
	Postprandial blood glucose (mg/dL)	Placebo/anagliptin	10.5±38.1 (31)	−42.4±50.3 (100)###
		Anagliptin/anagliptin	−34.4±52.7 (69)***

Notes: Mean ± standard deviation.

* P<0.05,

** P<0.01,

*** P<0.001 vs placebo group.

# P<0.05,

## P<0.01,

### P<0.001 vs baseline value. Copyright © 2012. Japanese Pharmacology and Therapeutics. Adapted from Kaku K. Efficacy and safety of anagliptin add-on therapy in Japanese patients with type 2 diabetes. Jpn Pharmacol Ther. 2012;40(9):745–770.²²

Table 3 Changes in the serum lipid concentrations in a Phase III trial

	Baseline	12 weeks	52 weeks	P
LDL-cholesterol
n	577	556	388
Measured value (mg/dL)	121.1±1.2	117.0±1.2	111.9±1.3	<0.001
Amount of change (mg/dL)	–	−3.6±0.9	−9.7±1.1
Rate of change (%)	–	−1.8±0.7	−6.5±0.9
Triglycerides
n	585	571	399
Measured value (mg/dL)	119.0	115.0	107	0.005
Amount of change (mg/dL)	–	−5.0	−5.0
Rate of change (%)	–	−4.7	−5.4
Total cholesterol
n	585	571	399
Measured value (mg/dL)	204.8±1.4	200.5±1.4	195.1±1.6	<0.001
Amount of change (mg/dL)	–	−4.2±1.0	−10.1±1.3
Rate of change (%)	–	−1.5±0.5	−4.1±0.6
HDL-cholesterol
n	585	571	399
Measured value (mg/dL)	56.2±0.6	55.9±0.6	55.9±0.7	<0.001
Amount of change (mg/dL)	–	−0.4±7.7	−0.1±0.4
Rate of change (%)	–	0.2±0.6	0.6±0.6
HDL-cholesterol (in subgroup with baseline value <40 mg/dL)
n	63	61	43
Measured value (mg/dL)	34.5±0.5	36.1±0.7	37.6±0.8	<0.001
Amount of change (mg/dL)	–	1.6±0.6	2.3±0.6
Rate of change (%)	–	5.4±2.0	6.9±1.9
Non HDL-cholesterol
n	585	571	399
Measured value (mg/dL)	148.6±1.4	144.5±1.5	139.2±1.5	<0.001
Amount of change (mg/dL)	–	−3.9±0.9	−10.0±1.3
Rate of change (%)	–	−1.7±0.7	−5.2±0.8

Notes: Mean ± SE. The P-value was measured according to a repeated-measures analysis of variance. Copyright © 2012. Japanese Pharmacology and Therapeutics. Adapted from Kaku K. Effects of anagliptin on serum lipids in Japanese patients with type 2 diabetes – a pooled analysis of long-term therapy with anagliptin. Jpn Pharmacol Ther. 2012;40(9):771–784.³¹

Abbreviations: LDL, low-density lipoprotein; HDL, high-density lipoprotein.

Table 4 Side effects observed in more than 2% of subjects treated with anagliptin and other oral antidiabetic agents in a Phase III trial in Japan

	Biguanides	α-Glucosidase inhibitors	Sulfonylureas	Thiazolidinediones
n	104	94	135	102
Total number	25 (24.0%)	22 (23.4%)	43 (31.9%)	23 (22.5%)
Abdominal fullness				2 (2.0%)
Constipation	3 (2.9%)	2 (2.1%)	7 (5.2%)	2 (2.0%)
Nasopharyngitis		2 (2.1%)
ALT elevation	7 (3.8%)		6 (4.4%)
AST elevation	3 (2.9%)
Serum amylase elevation	3 (2.9%)
γGTP elevation			3 (2.2%)
Hematocrit reduction		3 (4.2%)
Hemoglobin reduction		4 (4.3%)
Red blood cell count reduction		2 (2.1%)
Occult blood in stool	5 (4.8%)		5 (3.7%)
Hypoglycemia			10 (7.4%)	3 (2.9%)

Note: Copyright © 2012. Japanese Pharmacology and Therapeutics. Adapted from Kaku K. Efficacy and safety of anagliptin add-on therapy in Japanese patients with type 2 diabetes. Jpn Pharmacol Ther. 2012;40(9):745–770.²²

Abbreviations: ALT, aspartate aminotransferase; AST, alanine transaminase; γGTP, γ-glutamyltransferase.

AndoSTsugamiESuzukiSRecent trend in the prescription rates of antidiabetic agents in our facilityJournal of Japan Diabetes Society201356Suppl 1S164

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KakuKEfficacy and safety of anagliptin add-on therapy in Japanese patients with type 2 diabetesJpn Pharmacol Ther2012409745 770 Japanese [Abstract in English]

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KakuKEffects of anagliptin on serum lipids in Japanese patients with type 2 diabetes – a pooled analysis of long-term therapy with anagliptinJpn Pharmacol Ther2012409771 784 Japanese [Abstract in English]

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