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 9, September 2019, pages 651-663


Efficacy and Safety of Alogliptin in Elderly Patients With Type 2 Diabetes Mellitus

Figures

Figure 1.
Figure 1. Participant flow.
Figure 2.
Figure 2. Changes in eGFR (all patients). *P < 0.05 versus 0 month, paired t-test; **P < 0.05, ANOVA. eGFR: estimated glomerular filtration rate; ANOVA: analysis of variance.
Figure 3.
Figure 3. Changes in eGFR (patients newly receiving alogliptin). *P < 0.05 versus 0 month, paired t-test; **P < 0.05, ANOVA. eGFR: estimated glomerular filtration rate; ANOVA: analysis of variance.

Tables

Table 1. Baseline Characteristics
 
Age < 65Age 65 - 74Age ≥ 75PUnknown
Age < 65Age 65 - 74Age ≥ 75
*P < 0.05, Chi-square test (excluding “Unknown” cases); **P < 0.05, ANOVA. ANOVA: analysis of variance.
Male/female75 (68.2%)/33 (30%)46 (52.9%)/41 (47.1%)42 (45.2%)/49 (52.7%)0.009*2 (1.8%)0 (0%)2 (2.2%)
Age54.8 ± 7.969.7 ± 2.979.8 ± 3.8< 0.001**0 (0%)0 (0%)0 (0%)
Disease duration7.5 ± 5.511.5 ± 7.913 ± 8.4< 0.001**44 (40%)32 (36.8%)40 (43%)
Diabetic retinopathy6 (5.5%)11 (12.6%)6 (6.5%)0.24918 (16.4%)14 (16.1%)21 (22.6%)
Diabetic neuropathy4 (3.6%)9 (10.3%)13 (14%)0.08918 (16.4%)18 (20.7%)17 (18.3%)
Diabetic nephropathy12 (10.9%)10 (11.5%)12 (12.9%)0.83715 (13.6%)16 (18.4%)17 (18.3%)
Cerebrovascular disorders5 (4.5%)8 (9.2%)8 (8.6%)0.50219 (17.3%)15 (17.2%)21 (22.6%)
Myocardial infarction2 (1.8%)7 (8%)6 (6.5%)0.22319 (17.3%)15 (17.2%)21 (22.6%)
Angina pectoris4 (3.6%)13 (14.9%)13 (14%)0.029*19 (17.3%)14 (16.1%)21 (22.6%)
Arteriosclerosis obliterans2 (1.8%)4 (4.6%)4 (4.3%)0.47722 (20%)20 (23%)26 (28%)
Hypertension54 (49.1%)54 (62.1%)60 (64.5%)0.08214 (12.7%)12 (13.8%)13 (14%)
Dyslipidemia64 (58.2%)54 (62.1%)44 (47.3%)0.32714 (12.7%)12 (13.8%)16 (17.2%)
Hepatic steatosis26 (23.6%)16 (18.4%)6 (6.5%)0.016*22 (20%)23 (26.4%)29 (31.2%)
Others20 (18.2%)27 (31%)28 (30.1%)0.19230 (27.3%)18 (20.7%)24 (25.8%)
Smoking history24 (21.8%)22 (25.3%)12 (12.9%)0.28342 (38.2%)32 (36.8%)43 (46.2%)
Drinking history43 (39.1%)29 (33.3%)14 (15.1%)0.005*35 (31.8%)30 (34.5%)43 (46.2%)
Family history29 (26.4%)11 (12.6%)9 (9.7%)< 0.001*51 (46.4%)37 (42.5%)61 (65.6%)
Compliance with exercise; good or fair47 (42.7%)48 (55.2%)36 (38.7%)0.23251 (46.4%)30 (34.5%)46 (49.5%)
Compliance with diet therapy; good or fair49 (44.5%)47 (54%)40 (43%)0.32549 (44.5%)30 (34.5%)46 (49.5%)

 

Table 2. Medications of the Full Analysis Set
 
TimeAge < 65Age 65 - 74Age ≥ 75P*
DPP-4: dipeptidyl peptidase-4; M: month; N/A: not applicable. *P < 0.05 Chi-square test.
Number of applicable patients0 M1108793
12 M1007984
DPP-4 inhibitorsBefore27 (24.5%)28 (32.2%)21 (22.6%)0.302
0 M110 (100%)87 (100%)93 (100%)N/A
12 M100 (100%)79 (100%)84 (100%)N/A
SulfonylureaBefore38 (34.5%)38 (43.7%)41 (44.1%)0.289
0 M36 (32.7%)38 (43.7%)35 (37.6%)0.289
12 M40 (40%)34 (43%)32 (38.1%)0.811
BiguanideBefore36 (32.7%)20 (23%)14 (15.1%)0.013*
0 M39 (35.5%)24 (27.6%)14 (15.1%)0.004*
12 M50 (50%)24 (30.4%)17 (20.2%)< 0.001*
ThiazolidineBefore28 (25.5%)12 (13.8%)18 (19.4%)0.125
0 M22 (20%)14 (16.1%)16 (17.2%)0.758
12M22 (22%)9 (11.4%)15 (17.9%)0.178
α-glucosidase inhibitorsBefore25 (22.7%)20 (23%)26 (28%)0.639
0 M19 (17.3%)11 (12.6%)15 (16.1%)0.659
12 M13 (13%)10 (12.7%)12 (14.3%)0.948
GlinideBefore5 (4.5%)4 (4.6%)7 (7.5%)0.588
0 M0 (0%)0 (0%)0 (0%)N/A
12 M0 (0%)0 (0%)0 (0%)N/A
InsulinBefore0 (0%)1 (1.1%)0 (0%)0.310
0 M0 (0%)0 (0%)0 (0%)N/A
12 M0 (0%)0 (0%)1 (1.2%)0.343

 

Table 3. Efficacy Endpoints in the Full Analysis Set
 
Age < 65Age 65 - 74Age ≥ 75P (ANOVA)
nMeanSDP*nMeanSDP*nMeanSDP*
SD: standard deviation; ANOVA: analysis of variance; HbA1c: hemoglobin A1c; M: month; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; TG: triglyceride; GOT: glutamate oxaloacetate transaminase; GPT: glutamate pyruvate transaminase; γ-GTP: γ-glutamyl transpeptidase; SBP: systolic blood pressure; DBP: diastolic blood pressure; BMI: body mass index. *P < 0.05 versus 0 month, paired t-test; **P < 0.05, ANOVA.
HbA1c (%)0 M1107.651.32877.391.15937.061.020.002**
3 M1056.940.86846.900.71826.840.860.722
6 M936.840.81816.820.61826.640.710.132
9 M926.920.98716.800.67796.680.770.186
12 M966.901.07766.820.68766.740.810.513
Δ3 M105-0.731.02< 0.001*84-0.500.95< 0.001*82-0.300.900.004*0.010**
Δ6 M93-0.821.18< 0.001*81-0.500.97< 0.001*82-0.491.05< 0.001*0.066
Δ9 M92-0.731.28< 0.001*71-0.490.86< 0.001*79-0.411.100.001*0.155
Δ12 M96-0.741.45< 0.001*76-0.471.02< 0.001*76-0.421.110.002*0.180
Blood glucose (fasting) (mg/dL)0 M37162.057.727140.135.929142.735.80.111
3 M32134.730.823151.048.920125.627.30.073
6 M26126.830.323130.126.821132.722.70.756
9 M29139.339.721138.139.721124.123.00.287
12 M30132.148.419129.834.017134.135.50.955
Δ3 M27-32.946.60.001*189.440.90.34118-15.930.10.039*0.005**
Δ6 M22-23.437.40.008*19-16.430.20.029*20-18.122.60.002*0.749
Δ9 M24-25.356.30.038*18-10.029.30.16618-26.936.80.006*0.437
Δ12 M25-39.666.80.007*17-17.723.90.008*17-13.738.00.1570.197
Blood glucose (postprandial) (mg/dL)0 M42189.463.838180.363.637188.978.20.810
3 M39162.355.033147.431.934165.245.20.233
6 M42162.571.332161.247.633162.055.90.996
9 M36161.958.729154.38.528176.761.90.282
12 M40182.875.537160.944.436168.956.50.278
Δ3 M35-20.750.40.021*30-29.263.20.017*33-7.551.90.4150.291
Δ6 M33-24.444.00.003*30-1.758.60.87231-15.661.20.1650.264
Δ9 M31-23.358.60.035*26-5.946.90.525259.674.70.5250.136
Δ12 M36-6.666.30.55233-18.169.60.14533-2.266.70.8520.614
TC (mg/dL)0 M74197.335.848193.634.241185.127.40.178
3 M64192.535.544187.725.035182.531.70.314
6 M54187.031.140185.830.533187.833.00.959
9 M50186.129.931182.831.627176.830.70.449
12 M57188.532.634189.332.628181.430.10.560
Δ3 M63-3.030.40.43243-5.823.20.111320.328.70.9610.654
Δ6 M54-11.438.40.033*39-9.426.10.031*321.731.20.7660.194
Δ9 M49-15.333.30.002*31-12.125.50.013*26-3.723.50.4260.258
Δ12 M55-12.732.20.005*34-8.221.50.032*27-1.024.70.8410.199
LDL-C (mg/dL)0 M76119.130.368109.930.566108.524.20.055
3 M65113.827.063107.228.246105.124.30.187
6 M60109.328.954108.129.350104.825.70.697
9 M50106.322.844103.624.741104.328.10.865
12 M59110.226.852106.424.347103.323.30.361
Δ3 M62-6.531.50.10962-3.221.60.251441.415.80.5700.270
Δ6 M57-11.633.40.012*53-3.120.30.26949-3.720.80.2220.164
Δ9 M47-15.931.40.001*42-7.927.00.06440-3.321.90.3430.097
Δ12 M56-12.727.3< 0.001*52-6.829.50.10544-4.121.50.2080.252
HDL-C (mg/dL)0 M9052.012.46956.713.37456.013.60.046**
3 M8052.412.26656.214.45355.014.20.207
6 M7351.711.85456.012.65557.815.00.025**
9 M6752.013.44655.915.74656.213.80.209
12 M7553.012.15155.011.95557.515.40.167
Δ3 M780.97.30.27864-0.45.70.615510.27.90.8600.561
Δ6 M701.87.60.05754-2.17.40.043*551.78.00.1270.011**
Δ9 M630.37.80.77245-1.68.60.208460.87.30.4720.298
Δ12 M711.68.30.11051-2.46.70.015*530.97.90.4270.017**
TG (mg/dL)0 M92195.2193.577165.5119.874128.270.20.012**
3 M82177.4247.674153.1101.455133.389.80.328
6 M74177.9136.163148.093.157123.377.40.017**
9 M68164.4100.255147.285.448122.164.90.038**
12 M76154.278.361149.591.556123.762.50.073
Δ3 M80-4.4209.10.85073-11.795.90.300530.779.20.9480.893
Δ6 M73-37.3144.00.030*63-10.9104.10.40957-1.474.50.8850.175
Δ9 M66-49.1152.10.011*54-14.385.80.227481.252.60.8740.046**
Δ12 M72-24.0117.80.08961-7.582.30.470542.761.90.7480.268
GOT (IU/L)0 M7831.621.36926.212.96924.811.70.028**
3 M6729.218.06126.313.24825.711.00.377
6 M6228.016.35626.112.45223.78.50.221
9 M5328.917.64126.411.43825.620.70.623
12 M6428.918.05028.518.04824.611.60.335
Δ3 M65-3.118.00.16458-0.49.70.76646-0.25.50.8520.371
Δ6 M57-2.317.20.324550.411.40.80451-1.98.20.0970.507
Δ9 M51-3.015.20.159400.312.40.889381.59.40.3210.219
Δ12 M58-3.819.40.145502.515.60.25847-1.011.90.5830.135
GPT (IU/L)0 M9038.931.67627.317.97221.115.2< 0.001**
3 M8134.524.07025.518.25420.814.6< 0.001**
6 M7235.933.56126.015.65618.311.1< 0.001**
9 M6532.420.64926.115.54321.214.00.005**
12 M7835.229.35528.320.95018.59.2< 0.001**
Δ3 M78-5.419.60.017*67-1.212.70.43851-0.96.70.3300.139
Δ6 M68-3.331.70.39961-0.111.20.96453-2.510.70.0970.680
Δ9 M62-6.723.20.027*470.010.50.978410.97.80.4610.036**
Δ12 M72-5.226.80.106551.915.10.34849-2.512.30.1660.148
γ-GTP (IU/L)0 M8156.751.96545.057.27140.669.30.226
3 M6953.559.95845.261.85044.369.20.670
6 M6654.349.44952.466.15137.952.10.248
9 M5754.349.63761.890.44255.0123.50.915
12 M6849.042.94556.280.25036.661.80.281
Δ3 M66-4.520.30.07654-0.119.50.97249-0.616.70.8050.380
Δ6 M61-3.821.90.178482.846.60.68051-5.735.60.2560.451
Δ9 M54-3.423.90.302346.470.90.6024210.349.90.1880.363
Δ12 M62-5.127.70.151444.065.00.682500.767.80.9450.680
Serum amylase (IU/L)0 M3059.925.31767.019.31183.624.70.022**
3 M2164.923.01572.120.11188.623.50.023**
6 M1267.325.31371.420.31086.824.70.144
9 M563.614.9280.53.5480.017.40.250
12 M1055.916.5976.021.23113.029.50.001**
Δ3 M194.512.10.121146.820.60.24191.614.70.7590.746
Δ6 M128.09.70.016*1113.417.20.028*71.414.80.8070.229
Δ9 M42.38.30.62421.04.20.7954-4.827.00.7490.860
Δ12 M91.111.40.77789.921.70.2382-8.531.80.7700.392
Serum creatinine (mg/dL)0 M890.700.16650.730.27720.730.200.458
3 M770.720.17600.750.27560.800.400.283
6 M730.730.17520.750.27580.760.190.556
9 M660.740.16460.750.32490.730.200.856
12 M770.760.17510.760.28560.750.180.961
Δ3 M740.040.08< 0.001*570.000.080.692540.030.130.0930.160
Δ6 M690.030.080.002*520.020.100.122560.010.100.3550.578
Δ9 M620.040.07< 0.001*420.030.080.012*480.010.100.3780.157
Δ12 M700.060.08< 0.001*500.020.080.045*540.010.100.3190.016**
SBP (mm Hg)0 M108133.017.286132.313.391137.521.50.097
3 M103130.113.784131.114.787135.216.40.050
6 M91131.413.881130.814.183136.417.30.035**
9 M85131.313.473131.212.880134.015.40.359
12 M94132.017.075130.611.381134.817.90.244
Δ3 M101-2.615.20.09483-1.014.50.55187-2.718.10.1710.731
Δ6 M91-1.414.70.35280-1.413.70.35981-1.418.60.4981.000
Δ9 M85-2.015.60.24472-1.114.30.50179-3.821.10.1170.634
Δ12 M94-1.016.50.56774-1.715.20.33180-4.220.80.0740.465
DBP (mm Hg)0 M10880.011.48673.210.09174.010.4< 0.001**
3 M10378.411.78474.39.68772.69.6< 0.001**
6 M9178.511.18173.49.88272.48.7< 0.001**
9 M8479.511.37372.49.08071.99.6< 0.001**
12 M9479.610.87573.68.48172.69.8< 0.001**
Δ3 M101-1.49.40.132831.49.30.16487-1.712.40.1960.093
Δ6 M91-1.58.00.075800.38.30.71780-1.611.30.2110.325
Δ9 M84-0.710.80.55872-0.39.80.82979-1.911.40.1320.594
Δ12 M94-0.49.20.688740.29.90.86180-1.59.10.1480.524
Body weight (kg)0 M10473.0514.717762.5810.498557.5610.47< 0.001**
3 M8771.7313.606961.6410.286557.1111.50< 0.001**
6 M7972.5913.936561.2610.186656.5011.29< 0.001**
9 M7173.1113.755560.9010.546157.5111.04< 0.001**
12 M8074.6115.126261.6310.506457.4710.69< 0.001**
Δ3 M86-0.052.020.822680.002.121.00064-0.391.500.042*0.442
Δ6 M790.052.590.864640.254.190.63864-0.331.620.1120.538
Δ9 M710.012.400.98554-0.291.900.274600.072.470.8190.676
Δ12 M800.593.150.10161-0.252.070.34763-0.362.630.2840.072
BMI (kg/m2)0 M8526.614.636824.583.187323.553.23< 0.001**
3 M6926.384.216024.263.175423.143.43< 0.001**
6 M6226.724.145724.213.285423.163.30< 0.001**
9 M5326.683.874923.793.215023.583.15< 0.001**
12 M6227.214.755524.073.275423.453.03< 0.001**
Δ3 M680.050.610.482600.000.890.98154-0.190.650.037*0.166
Δ6 M620.070.960.588570.161.800.51153-0.180.710.0660.337
Δ9 M530.050.900.66949-0.070.740.521500.071.050.6480.713
Δ12 M620.231.160.11555-0.090.800.40254-0.151.150.3290.101