J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 7, Number 4, April 2015, pages 211-219

Efficacy and Safety of Sitagliptin in Japanese Patients With Type 2 Diabetes

**Table 1.** Baseline Characteristics of Study Subjects (n = 3,201)
Baseline parameters
Data are mean ± SD or number or % of subjects.
Age (years) (n = 3,201)	65.0 ± 11.4
Gender (male/female) (n = 3,198)	1,911/1,287
Body mass index (kg/m²) (n = 2,845)	25.1 ± 4.3
Estimated duration of diabetes (years) (n = 2,914)	9.56 ± 7.58
HbA1c (NGSP) (%) (n = 3,132)	7.44 ± 1.20
Estimated glomerular filtration rate (mL/min/1.73 m²) (n = 2,702)	69.2 ± 47.6
Glucose lowering agents (%)
Sulfonylurea	59.40%
Glinide	2.20%
α-glucosidase inhibitor	13.80%
Thiazolidinedione	23.40%
Metformin	45.50%
Insulin therapy	8.80%

Table 1. Baseline Characteristics of Study Subjects (n = 3,201)

Baseline parameters

Data are mean ± SD or number or % of subjects.

Age (years) (n = 3,201)

65.0 ± 11.4

Gender (male/female) (n = 3,198)

1,911/1,287

Body mass index (kg/m²) (n = 2,845)

25.1 ± 4.3

Estimated duration of diabetes (years) (n = 2,914)

9.56 ± 7.58

HbA1c (NGSP) (%) (n = 3,132)

7.44 ± 1.20

Estimated glomerular filtration rate (mL/min/1.73 m²) (n = 2,702)

69.2 ± 47.6

Glucose lowering agents (%)

Sulfonylurea

59.40%

Glinide

2.20%

α-glucosidase inhibitor

13.80%

Thiazolidinedione

23.40%

Metformin

45.50%

Insulin therapy

8.80%

**Table 2.** Changes in Clinical Parameters After Sitagliptin Treatment (n = 3,201)
	Baseline	At 1 month	At 3 months	At 6 months	P value*
Data are mean ± SD or number of subjects. Changes in clinical parameters after sitagliptin treatment were evaluated by analysis of variance using mixed effects model. *Comparison between baseline value and each value at 1, 3 and 6 months, by Student’s t-test. P < 0.05. NGSP: National Glycohemoglobin Standardization Program.
Body mass index (kg/m²)	25.1 ± 4.3	25.2 ± 4.3	25.2 ± 4.3	25.6 ± 4.3	NS
n	2,845	1,937	2,026	1,512
HbA1c (NGSP) (%)	7.44 ± 1.20	7.07 ± 1.03**	6.75 ± 0.92**	6.73 ± 0.99**	< 0.0001
n	3,132	2,848	2,959	2,946
Random blood glucose level (mmo/L)	9.69 ± 3.56	8.42 ± 2.88**	8.32 ± 2.78**	8.47 ± 2.91**	< 0.0001
n	3,102	2,858	2,946	2,923

Table 2. Changes in Clinical Parameters After Sitagliptin Treatment (n = 3,201)

Baseline

At 1 month

At 3 months

At 6 months

P value*

Data are mean ± SD or number of subjects. *Changes in clinical parameters after sitagliptin treatment were evaluated by analysis of variance using mixed effects model. **Comparison between baseline value and each value at 1, 3 and 6 months, by Student’s t-test. P < 0.05. NGSP: National Glycohemoglobin Standardization Program.

Body mass index (kg/m²)

25.1 ± 4.3

25.2 ± 4.3

25.6 ± 4.3

2,845

1,937

2,026

1,512

HbA1c (NGSP) (%)

7.44 ± 1.20

7.07 ± 1.03**

6.75 ± 0.92**

6.73 ± 0.99**

< 0.0001

3,132

2,848

2,959

2,946

Random blood glucose level (mmo/L)

9.69 ± 3.56

8.42 ± 2.88**

8.32 ± 2.78**

8.47 ± 2.91**

< 0.0001

3,102

2,858

2,946

2,923

**Table 3.** Predictive Value of Baseline Clinical Parameters for HbA1c Reduction by Sitagliptin Using Linear Mixed Effect Model (Type III Tests of Fixed Effects) (n = 3,201)
Effect	Numerator of degree of freedom	Denominator of degree of freedom	F value	Pr > F
Age (< 65 vs. ≥ 65), gender (male vs. female), duration of type 2 diabetes (< 10 years vs. ≥ 10 years), BMI (< 25 vs. ≥ 25), HbA1c levels (6, vs. 6 - 6.9 vs. 7.0 - 7.9 vs. ≥ 8), eGFR (60, vs. ≥ 60) and type of anti-diabetes drugs (sitagliptin monotherapy vs. sitagliptin plus SU vs. sitagliptin plus OHA and/or insulin without SU) were entered as covariate. eGFR: estimated glomerular filtration rate; NGSP: National Glycohemoglobin Standardization Program.
Treatment period	3	8,076	839.64	< 0.001
Treatment period × body mass index (kg/m²)	3	8,076	0.91	0.4330
Age (years)	1	3,071	9.29	0.0023
Gender (female/male)	1	3,071	0.07	0.7871
Body mass index (kg/m²)	1	3,071	4.44	0.0353
Estimated duration of diabetes (years)	1	3,071	2.42	0.1202
Baseline HbA1c levels (%) (NGSP)	3	3,071	1,512.15	< 0.001
eGFR (mL/min/1.73 m²)	1	3,071	1.94	0.1640
Type of diabetes drugs	2	3,071	7.90	0.0004

Table 3. Predictive Value of Baseline Clinical Parameters for HbA1c Reduction by Sitagliptin Using Linear Mixed Effect Model (Type III Tests of Fixed Effects) (n = 3,201)

Effect

Numerator of degree of freedom

Denominator of degree of freedom

F value

Pr > F

Age (< 65 vs. ≥ 65), gender (male vs. female), duration of type 2 diabetes (< 10 years vs. ≥ 10 years), BMI (< 25 vs. ≥ 25), HbA1c levels (6, vs. 6 - 6.9 vs. 7.0 - 7.9 vs. ≥ 8), eGFR (60, vs. ≥ 60) and type of anti-diabetes drugs (sitagliptin monotherapy vs. sitagliptin plus SU vs. sitagliptin plus OHA and/or insulin without SU) were entered as covariate. eGFR: estimated glomerular filtration rate; NGSP: National Glycohemoglobin Standardization Program.

Treatment period

8,076

839.64

< 0.001

Treatment period × body mass index (kg/m²)

8,076

0.91

0.4330

Age (years)

3,071

9.29

0.0023

Gender (female/male)

3,071

0.07

0.7871

Body mass index (kg/m²)

3,071

4.44

0.0353

Estimated duration of diabetes (years)

3,071

2.42

0.1202

Baseline HbA1c levels (%) (NGSP)

3,071

1,512.15

< 0.001

eGFR (mL/min/1.73 m²)

3,071

1.94

0.1640

Type of diabetes drugs

3,071

7.90

0.0004

**Table 4.** Clinical and Laboratory Safety and Tolerability Results (n = 3,201)
	Number of patients with clinical adverse effects	Number of patients who discontinued due to adverse effects
*Data are number of subjects (%).
Hypoglycemia	82 (2.5%)	4
Constipation	29 (0.90%)	7
Dizziness	25 (0.77%)	4
Eruption	24 (0.74%)	10
Edema	20 (0.62%)	1
Liver dysfunction	19 (0.59%)	5
Abdominal distension	18 (0.56%)	4
Diarrhea	10 (0.31%)	2
Abdominal pain	8 (0.25%)	1
Nausea and vomiting	7 (0.22%)	1
Appetite loss	3 (0.09%)	0
Others	78 (2.4%)	14
Total	323 (10.1%)	53

Table 4. Clinical and Laboratory Safety and Tolerability Results (n = 3,201)

Number of patients with clinical adverse effects

Number of patients who discontinued due to adverse effects

*Data are number of subjects (%).

Hypoglycemia

82 (2.5%)

Constipation

29 (0.90%)

Dizziness

25 (0.77%)

Eruption

24 (0.74%)

Edema

20 (0.62%)

Liver dysfunction

19 (0.59%)

Abdominal distension

18 (0.56%)

Diarrhea

10 (0.31%)

Abdominal pain

8 (0.25%)

Nausea and vomiting

7 (0.22%)

Appetite loss

3 (0.09%)

Others

78 (2.4%)

Total

323 (10.1%)

**Table 5.** Predictors of Hypoglycemia by Multiple Logistic Regression (n = 3,201)
Variables at baseline	Odds ratio (Wald 95% confidence interval)
NGSP: National Glycohemoglobin Standardization Program.
Type of anti-diabetes drugs
Sitagliptin plus SU vs. sitagliptin monotherapy	16.25 (7.633 - 34.61)
Sitagliptin plus OHA and/or insulin without SU vs. sitagliptin monotherapy	6.23 (2.75 - 14.36)
Female vs. male	1.47 (1.17 - 1.85)
Body mass index (< 25 vs. ≥ 25)	1.95 (1.52 - 2.50)
Estimated duration of diabetes (years) (≥ 10 vs. < 10)	1.28 (1.02 - 1.62)
Baseline HbA1c level (%) (NGSP)
< 6 vs. ≥ 8	0.35 (0.13 - 0.96)
6.0 - 6.9 vs. ≥ 8	1.17 (0.87 - 1.58)
7.0 - 7.9 vs. ≥ 8	1.14 (0.85 - 1.52)

Table 5. Predictors of Hypoglycemia by Multiple Logistic Regression (n = 3,201)

Variables at baseline

Odds ratio (Wald 95% confidence interval)

NGSP: National Glycohemoglobin Standardization Program.

Type of anti-diabetes drugs

Sitagliptin plus SU vs. sitagliptin monotherapy

16.25 (7.633 - 34.61)

Sitagliptin plus OHA and/or insulin without SU vs. sitagliptin monotherapy

6.23 (2.75 - 14.36)

Female vs. male

1.47 (1.17 - 1.85)

Body mass index (< 25 vs. ≥ 25)

1.95 (1.52 - 2.50)

Estimated duration of diabetes (years) (≥ 10 vs. < 10)

1.28 (1.02 - 1.62)

Baseline HbA1c level (%) (NGSP)

< 6 vs. ≥ 8

0.35 (0.13 - 0.96)

6.0 - 6.9 vs. ≥ 8

1.17 (0.87 - 1.58)

7.0 - 7.9 vs. ≥ 8

1.14 (0.85 - 1.52)