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 11, Number 5, May 2019, pages 311-320


Efficacy and Safety of Adding Sitagliptin in Type 2 Diabetes Patients on Insulin: Age-Stratified Comparison at One Year in the ASSIST-K Study

Figures

Figure 1.
Figure 1. Changes of HbA1c. SD: standard deviation.
Figure 2.
Figure 2. Changes of body weight. SD: standard deviation.
Figure 3.
Figure 3. Changes of eGFR. SD: standard deviation.

Tables

Table 1. Baseline Demographic Factors: All Patients on Insulin Receiving Add-on Sitagliptin Versus Patients With Sufficient HbA1c Data
 
All patients on insulinPatients with HbA1c data
Men: eGFR = 194 × serum creatinine-1.094 × age at enrollment-0.287; Women: eGFR = 194 × serum creatinine-1.094 × age at enrollment-0.287 × 0.739. Data are shown as the mean ± standard deviation unless otherwise noted. BMI: body mass index; eGFR; estimated glomerular filtration rate; HbA1c: hemoglobin A1c; NGSP: National Glycohemoglobin Standardization Program.
No. of patients937 (100.0%)821 (100.0%)
Sex
  Male508 (54.2%)440 (53.6%)
  Female429 (45.8%)381 (46.4%)
Age at enrollment63.9 ± 12.364.2 ± 11.9
Diabetic complications
  Retinopathy315 (33.6%)285 (34.7%)
  Neuropathy324 (34.6%)296 (36.1%)
  Nephropathy367 (39.2%)336 (40.9%)
Arteriosclerotic diseases
  Cerebrovascular disease72 (7.7%)65 (7.9%)
  Myocardial infarction/angina pectoris162 (17.3%)142 (17.3%)
  Arteriosclerosis obliterans87 (9.3%)81 (9.9%)
Other complications
  Hypertension531 (56.7%)478 (58.2%)
  Dyslipidemia588 (62.8%)523 (63.7%)
  Fatty liver308 (32.9%)272 (33.1%)
History of smoking238 (25.4%)207 (25.2%)
History of alcohol intake231 (24.7%)192 (23.4%)
Duration of diabetes (years)17.0 ± 9.217.2 ± 9.1
Weight (baseline)66.23 ± 15.5166.15 ± 14.99
BMI (baseline)25.38 ± 4.6125.38 ± 4.48
HbA1c (baseline) (NGSP, %)8.50 ± 1.358.49 ± 1.34
eGFR (baseline) (mL/min/1.73 m2)75.851 ± 22.90575.588 ± 22.502

 

Table 2. Demographic Factors of Each Age Group
 
Age at enrollmentIntergroup comparison: P value
A) ≤ 64 yearsB) 65 - 74 yearsC) ≥ 75 yearsA vs. BA vs. CB vs. C
*P < 0.050, **P < 0.010, and ***P < 0.001. Data are shown as the mean ± standard deviation unless otherwise noted. BMI: body mass index; eGFR; estimated glomerular filtration rate; HbA1c: hemoglobin A1c; NGSP: National Glycohemoglobin Standardization Program.
No. of patients analyzed389 (100.0%)267 (100.0%)165 (100.0%)
Sex
  Male237 (60.9%)126 (47.2%)77 (46.7%)Fisher’s exact test
  Female152 (39.1%)141 (52.8%)88 (53.3%)< 0.001***0.003**0.921
Age at enrollment54.0 ± 8.369.6 ± 2.979.2 ± 3.4t-test
  N389267165< 0.001***< 0.001***< 0.001***
Diabetic complications
  Retinopathy
    No222 (57.1%)131 (49.1%)84 (50.9%)Fisher’s exact test
    Yes124 (31.9%)102 (38.2%)59 (35.8%)0.0570.2610.668
  Neuropathy
    No223 (57.3%)128 (47.9%)68 (41.2%)Fisher’s exact test
    Yes114 (29.3%)108 (40.4%)74 (44.8%)0.004**< 0.001***0.244
  Nephropathy
    No194 (49.9%)124 (46.4%)69 (41.8%)Fisher’s exact test
    Yes146 (37.5%)113 (42.3%)77 (46.7%)0.270.048*0.346
Arteriosclerotic diseases
  Cerebrovascular disease
    No311 (79.9%)199 (74.5%)121 (73.3%)Fisher’s exact test
    Yes16 (4.1%)32 (12.0%)17 (10.3%)< 0.001***0.009**0.752
  Myocardial infarction
    No287 (73.8%)176 (65.9%)96 (58.2%)Fisher’s exact test
  Angina pectoris
    Yes40 (10.3%)60 (22.5%)42 (25.5%)< 0.001***< 0.001***0.336
  Arteriosclerosis
    No285 (73.3%)199 (74.5%)118 (71.5%)Fisher’s exact test
  Obliterans
    Yes33 (8.5%)29 (10.9%)19 (11.5%)0.4140.3350.752
Other complications
  Hypertension
    No157 (40.4%)80 (30.0%)35 (21.2%)Fisher’s exact test
    Yes192 (49.4%)167 (62.5%)119 (72.1%)0.002**< 0.001***0.041*
  Dyslipidemia
    No106 (27.2%)68 (25.5%)57 (34.5%)Fisher’s exact test
    Yes252 (64.8%)178 (66.7%)93 (56.4%)0.6480.0760.035*
  Fatty liver
    No152 (39.1%)129 (48.3%)83 (50.3%)Fisher’s exact test
    Yes146 (37.5%)82 (30.7%)44 (26.7%)0.024*0.008**0.486
History of smoking
  No167 (42.9%)125 (46.8%)84 (50.9%)Fisher’s exact test
  Yes120 (30.8%)59 (22.1%)28 (17.0%)0.041*0.002**0.237
History of alcohol intake
  No165 (42.4%)113 (42.3%)90 (54.5%)Fisher’s exact test
  Yes114 (29.3%)58 (21.7%)20 (12.1%)0.162< 0.001***0.004**
Duration of diabetes (years)13.6 ± 7.219.8 ± 8.621.3 ± 10.5t-test
  N331227141< 0.001***< 0.001***0.123
Body weight (baseline)72.06 ± 16.1462.40 ± 11.3058.23 ± 11.48t-test
  N389267164< 0.001***< 0.001***< 0.001*
BMI (baseline)26.58 ± 4.8124.55 ± 3.7423.89 ± 4.03t-test
  N376256159< 0.001***< 0.001***0.089
HbA1c (baseline) (NGSP, %)8.80 ± 1.508.24 ± 1.098.19 ± 1.13t-test
  N389267165< 0.001***< 0.001***0.644
eGFR (baseline) (mL/min/1.73 m2)85.1 ± 21.770.0 ± 19.763.2 ± 18.8t-test
  N285176140< 0.001***< 0.001***0.002**

 

Table 3. Antidiabetic Agents
 
Age at enrollmentIntergroup comparison: P value
A) ≤ 64 yearsB) 65 - 74 yearsC) ≥ 75 yearsA vs. BA vs. CB vs. C
*P < 0.050, **P < 0.010, and ***P < 0.001. Data are shown as the mean ± standard deviation unless otherwise noted. NA: not applicable; OHA: oral hypoglycemic agent.
No. of patients analyzed389 (100.0%)267 (100.0%)165 (100.0%)
Before sitagliptin therapy
  Daily no. of insulin doses
    00 (0.0%)0 (0.0%)0 (0.0%)Wilcoxon test
    171 (18.3%)53 (19.9%)39 (23.6%)0.2660.002**0.031*
    281 (20.8%)55 (20.6%)53 (32.1%)
    3103 (26.5%)83 (31.1%)33 (20.0%)
    4134 (34.4%)76 (28.5%)40 (24.2%)
    Mean2.82.72.4
  OHAsFisher’s exact test
    Sulfonylureas76 (19.5%)60 (22.5%)34 (20.6%)0.3790.8160.719
    Biguanides200 (51.4%)98 (36.7%)39 (23.6%)< 0.001***< 0.001***0.006**
    Thiazolidinediones54 (13.9%)24 (9.0%)12 (7.3%)0.0650.031*0.594
    Alpha-glucosidase inhibitors102 (26.2%)71 (26.6%)43 (26.1%)0.92811
    Glinides6 (1.5%)4 (1.5%)5 (3.0%)10.3170.312
  Number of OHAs
    0122 (31.4%)107 (40.1%)69 (41.8%)Wilcoxon test
    1138 (35.5%)80 (30.0%)66 (40.0%)0.036*< 0.001***0.127
    290 (23.1%)65 (24.3%)24 (14.5%)
    339 (10.0%)15 (5.6%)6 (3.6%)
    Mean1.110.8
At the start of sitagliptin therapy
  Sitagliptin dose47.1 ± 9.745.1 ± 11.345.0 ± 10.0Wilcoxon test
    N3882671650.009**0.027*0.927
  Daily no. of insulin doses
    01 (0.3%)1 (0.4%)0 (0.0%)Wilcoxon test
    171 (18.3%)56 (21.0%)41 (24.8%)0.190.003**0.064
    285 (21.9%)56 (21.0%)50 (30.3%)
    3100 (25.7%)80 (30.0%)35 (21.2%)
    4132 (33.9%)74 (27.7%)39 (23.6%)
    Mean2.72.62.4
  OHAsFisher’s exact test
    Sulfonylureas74 (19.0%)60 (22.5%)31 (18.8%)0.32410.397
    Biguanides196 (50.4%)94 (35.2%)31 (18.8%)< 0.001***< 0.001***< 0.001***
    Thiazolidinediones33 (8.5%)13 (4.9%)9 (5.5%)0.0870.2920.824
    Alpha-glucosidase inhibitors74 (19.0%)57 (21.3%)30 (18.2%)0.4870.9050.46
    Glinides1 (0.3%)0 (0.0%)0 (0.0%)NANANA
  No. of concomitant OHAs
    0137 (35.2%)122 (45.7%)90 (54.5%)Wilcoxon test
    1145 (37.3%)76 (28.5%)54 (32.7%)0.040*< 0.001***0.010*
    288 (22.6%)59 (22.1%)17 (10.3%)
    319 (4.9%)10 (3.7%)4 (2.4%)
    Mean10.80.6
After 12 months of sitagliptin therapy
  Sitagliptin dose52.8 ± 15.651.7 ± 17.250.3 ± 11.8Wilcoxon test
    N3842641620.1480.1210.898
  Daily no. of insulin doses
    07 (1.8%)3 (1.1%)3 (1.8%)Wilcoxon test
    170 (18.0%)60 (22.5%)43 (26.1%)0.039*0.007**0.287
    277 (19.8%)55 (20.6%)45 (27.3%)
    3102 (26.2%)83 (31.1%)28 (17.0%)
    4133 (34.2%)66 (24.7%)46 (27.9%)
    Mean2.72.62.4
  OHAsFisher’s exact test
    Sulfonylureas66 (17.0%)47 (17.6%)36 (21.8%)0.8340.1880.315
    Biguanides172 (44.2%)74 (27.7%)25 (15.2%)< 0.001***< 0.001***0.003**
    Thiazolidinediones35 (9.0%)15 (5.6%)8 (4.8%)0.1340.1180.828
    Alpha-glucosidase inhibitors75 (19.3%)51 (19.1%)34 (20.6%)10.7270.71
    Glinides0 (0.0%)0 (0.0%)0 (0.0%)NANANA
  Number of concomitant OHAs
    0160 (41.1%)137 (51.3%)90 (54.5%)Wilcoxon test
    1125 (32.1%)79 (29.6%)51 (30.9%)0.005**< 0.001***0.366
    289 (22.9%)45 (16.9%)20 (12.1%)
    315 (3.9%)6 (2.2%)4 (2.4%)
    Mean0.90.70.6

 

Table 4. Adverse Events
 
All patientsAge at enrollmentIntergroup comparison: P value
A) ≤ 64 yearsB) 65 - 74 yearsC) ≥ 75 yearsA vs. BA vs. CB vs. C
No. of patients analyzed821 (100.0%)389 (100.0%)267 (100.0%)165 (100.0%)Fisher’s exact test
Severe hypoglycemia24 (2.9%)12 (3.1%)8 (3.0%)4 (2.4%)1.0000.7871.000
Gastrointestinal symptoms9 (1.1%)5 (1.3%)3 (1.1%)1 (0.6%)1.0000.6751.000
Constipation20 (2.4%)9 (2.3%)4 (1.5%)7 (4.2%)0.5750.2660.114
Others20 (2.4%)5 (1.3%)9 (3.4%)6 (3.6%)0.0970.0931.000