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 8, August 2015, pages 607-612

Factors Predicting Therapeutic Efficacy of Combination Treatment With Sitagliptin and Insulin in Type 2 Diabetic Patients: The ASSIST-K Study

Figure 1. Changes in hemoglobin A_1c, body weight, and insulin dose (n = 1,004). Data are the mean ± standard deviation. Analysis of variance vs. baseline. *P < 0.05. M: months.

**Table 1.** Characteristics of the Subjects
Data are mean ± standard deviation unless otherwise indicated.
Age, years	63.9 ± 12.1
Sex, male/female	521/483
Body mass index	25.5 ± 4.6
Hemoglobin A_1c, % (mmol/mol)	8.69 ± 1.31 (72 ± 12)
Fasting blood glucose, mg/dL (mmol/L)	184.3 ± 70.5 (10.23 ± 3.91)
Serum C-peptide, ng/mL (nmol/L)	1.47 ± 1.03 (0.49 ± 0.34)
Duration of diabetes, years	17.1 ± 9.0
Duration of insulin treatment, years	6.3 ± 5.6
Smoking, %	23.1
Alcohol consumption, %	22.7
Complications, %
Diabetic neuropathy	33.6
Diabetic retinopathy	33.4
Diabetic nephropathy	38.5
Cerebrovascular disease	7.6
Myocardial infarction/angina pectoris	17.3
Arteriosclerosis obliterans	8.8
Hypertension	57.7
Dyslipidemia	61.4
Hepatic steatosis	30.0
Insulin regimen, n
Long-acting insulin, once daily	215
Mixed insulin, twice daily	162
Three times daily, no long-acting insulin	209
Basal-bolus insulin	334
Concomitant oral medications, n
Sulfonylureas	222
Biguanides	397
Thiazolidinediones	64
Alpha-glucosidase inhibitors	184
None	418
Dose of sitagliptin, n
25 mg throughout	65
Up-titration from 25 mg to 50 mg	83
50 mg throughout	809
Up-titration from 50 mg to 100 mg	47

Table 1. Characteristics of the Subjects

Data are mean ± standard deviation unless otherwise indicated.

Age, years

63.9 ± 12.1

Sex, male/female

521/483

Body mass index

25.5 ± 4.6

Hemoglobin A_1c, % (mmol/mol)

8.69 ± 1.31 (72 ± 12)

Fasting blood glucose, mg/dL (mmol/L)

184.3 ± 70.5 (10.23 ± 3.91)

Serum C-peptide, ng/mL (nmol/L)

1.47 ± 1.03 (0.49 ± 0.34)

Duration of diabetes, years

17.1 ± 9.0

Duration of insulin treatment, years

6.3 ± 5.6

Smoking, %

23.1

Alcohol consumption, %

22.7

Complications, %

Diabetic neuropathy

33.6

Diabetic retinopathy

33.4

Diabetic nephropathy

38.5

Cerebrovascular disease

7.6

Myocardial infarction/angina pectoris

17.3

Arteriosclerosis obliterans

8.8

Hypertension

57.7

Dyslipidemia

61.4

Hepatic steatosis

30.0

Insulin regimen, n

Long-acting insulin, once daily

215

Mixed insulin, twice daily

162

Three times daily, no long-acting insulin

209

Basal-bolus insulin

334

Concomitant oral medications, n

Sulfonylureas

222

Biguanides

397

Thiazolidinediones

Alpha-glucosidase inhibitors

184

None

418

Dose of sitagliptin, n

25 mg throughout

Up-titration from 25 mg to 50 mg

50 mg throughout

809

Up-titration from 50 mg to 100 mg

**Table 2.** Changes in Laboratory Values
Clinical parameter	n	Baseline	1 month	3 months	6 months	Difference between baseline and 6 months
^aP < 0.05 (analysis of variance vs. baseline). BP: blood pressure; HDL: high-density lipoprotein; LDL: low-density lipoprotein.
Systolic BP, mm Hg	923	130.82	130.85	130.38	130.28
Diastolic BP, mm Hg	923	74.97	74.66^a	74.03^a	74.22^a	-0.75
Fasting blood glucose, mg/dL (mmol/L)	199	181.35 (10.06)	160.62 (8.91)^a	164.81 (9.15)^a	160.9 (8.93)^a	-20.45 (-1.13)
Serum C-peptide, ng/dL (nmol/L)	53	0.91 (0.30)	0.98 (0.32)	1 (0.33)	0.96 (0.32)
Glycated albumin, %	53	23.2	21.61^a	21.05^a	21.03^a	-2.17
Aspartate aminotransferase, IU/L (µkat/L)	773	27.62 (0.46)	26.41 (0.44)	27.02 (0.45)	27.56 (0.46)
Alanine aminotransferase, IU/L (µkat/L)	770	24.66 (0.41)	24.11 (0.40)	24.79 (0.41)	24.22 (0.40)
Gamma-glutamyl transpeptidase, IU/L	703	44.12	42.22	42.12	43.47
Alkaline phosphatase, mg/dL	175	260.05	254.16^a	241.82^a	241.83^a	-18.22
Total cholesterol, mg/dL (mmol/L)	453	194.72 (5.04)	191.56 (4.96)^a	190.26 (4.93)^a	191.39 (4.96)^a	-3.33 (-0.08)
LDL cholesterol, mg/dL (mmol/L)	733	109.66 (2.84)	109.02 (2.82)	108.67 (2.81)	109.08 (2.83)
HDL cholesterol, mg/dL (mmol/L)	794	55.62 (1.44)	55.05 (1.43)^a	54.8 (1.42)^a	54.72 (1.42)^a	-0.90 (-0.02)
Triglycerides, mg/dL (mmol/L)	805	164.12 (1.85)	153.61 (1.74)^a	153.3 (1.73)^a	155.33 (1.76)^a	-8.79 (-0.09)
Uric acid, mg/dL (µmol/L)	331	5.05 (300.40)	5.18 (308.13)^a	5.32 (316.46)^a	5.27 (313.49)^a	+0.25 (+13.09)
Creatinine, mg/dL (µmol/L)	674	0.76 (67.18)	0.77 (68.07)^a	0.78 (68.95)^a	0.79 (69.84)^a	+0.03 (+2.66)

Table 2. Changes in Laboratory Values

Clinical parameter

Baseline

1 month

3 months

6 months

Difference between baseline and 6 months

^aP < 0.05 (analysis of variance vs. baseline). BP: blood pressure; HDL: high-density lipoprotein; LDL: low-density lipoprotein.

Systolic BP, mm Hg

923

130.82

130.85

130.38

130.28

Diastolic BP, mm Hg

923

74.97

74.66^a

74.03^a

74.22^a

-0.75

Fasting blood glucose, mg/dL (mmol/L)

199

181.35 (10.06)

160.62 (8.91)^a

164.81 (9.15)^a

160.9 (8.93)^a

-20.45 (-1.13)

Serum C-peptide, ng/dL (nmol/L)

0.91 (0.30)

0.98 (0.32)

1 (0.33)

0.96 (0.32)

Glycated albumin, %

23.2

21.61^a

21.05^a

21.03^a

-2.17

Aspartate aminotransferase, IU/L (µkat/L)

773

27.62 (0.46)

26.41 (0.44)

27.02 (0.45)

27.56 (0.46)

Alanine aminotransferase, IU/L (µkat/L)

770

24.66 (0.41)

24.11 (0.40)

24.79 (0.41)

24.22 (0.40)

Gamma-glutamyl transpeptidase, IU/L

703

44.12

42.22

42.12

43.47

Alkaline phosphatase, mg/dL

175

260.05

254.16^a

241.82^a

241.83^a

-18.22

Total cholesterol, mg/dL (mmol/L)

453

194.72 (5.04)

191.56 (4.96)^a

190.26 (4.93)^a

191.39 (4.96)^a

-3.33 (-0.08)

LDL cholesterol, mg/dL (mmol/L)

733

109.66 (2.84)

109.02 (2.82)

108.67 (2.81)

109.08 (2.83)

HDL cholesterol, mg/dL (mmol/L)

794

55.62 (1.44)

55.05 (1.43)^a

54.8 (1.42)^a

54.72 (1.42)^a

-0.90 (-0.02)

Triglycerides, mg/dL (mmol/L)

805

164.12 (1.85)

153.61 (1.74)^a

153.3 (1.73)^a

155.33 (1.76)^a

-8.79 (-0.09)

Uric acid, mg/dL (µmol/L)

331

5.05 (300.40)

5.18 (308.13)^a

5.32 (316.46)^a

5.27 (313.49)^a

+0.25 (+13.09)

Creatinine, mg/dL (µmol/L)

674

0.76 (67.18)

0.77 (68.07)^a

0.78 (68.95)^a

0.79 (69.84)^a

+0.03 (+2.66)

**Table 3.** Multiple Regression Analysis of Delta Hemoglobin A_1c After 6 Months of Insulin-Sitagliptin Combination Therapy in 495 Patients With Complete Data
Factor	Beta value	P value	Standardized beta value
Age	-0.010	0.0088	-0.124
Female sex	0.164	0.0802	0.080
Baseline body mass index	0.030	0.0048	0.136
Duration of insulin treatment, years	0.013	0.1383	0.065
Baseline hemoglobin A_1c	-0.400	< 0.0001	-0.502
Baseline daily insulin dose	0.002	0.2401	0.057
Presence of diabetic neuropathy	0.051	0.5512	0.025
Smoking, yes	0.004	0.9694	0.002
Alcohol consumption, yes	-0.004	0.9683	-0.002
Sulfonylureas	0.191	0.0939	0.074
Biguanides	-0.162	0.0720	-0.078
Thiazolidinediones	-0.300	0.0800	-0.072
Alpha-glucosidase inhibitors	-0.096	0.3606	-0.037

Table 3. Multiple Regression Analysis of Delta Hemoglobin A_1c After 6 Months of Insulin-Sitagliptin Combination Therapy in 495 Patients With Complete Data

Factor

Beta value

P value

Standardized beta value

Age

-0.010

0.0088

-0.124

Female sex

0.164

0.0802

0.080

Baseline body mass index

0.030

0.0048

0.136

Duration of insulin treatment, years

0.013

0.1383

0.065

Baseline hemoglobin A_1c

-0.400

< 0.0001

-0.502

Baseline daily insulin dose

0.002

0.2401

0.057

Presence of diabetic neuropathy

0.051

0.5512

0.025

Smoking, yes

0.004

0.9694

0.002

Alcohol consumption, yes

-0.004

0.9683

-0.002

Sulfonylureas

0.191

0.0939

0.074

Biguanides

-0.162

0.0720

-0.078

Thiazolidinediones

-0.300

0.0800

-0.072

Alpha-glucosidase inhibitors

-0.096

0.3606

-0.037