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Original Article
Predictive Factors for the Therapeutic Response to Concomitant Treatment with DPP-4 Inhibitors in Type 2 Diabetes with Short-Term Follow-Up
Jong-Ha Baek1, Bo Ra Kim1, Jeong Woo Hong1, Soo Kyoung Kim1,2, Jung Hwa Jung1,2, Jaehoon Jung1,2, Jong Ryeal Hahm1,2
Kosin Medical Journal 2016;31(2):146-156.
DOI: https://doi.org/10.7180/kmj.2016.31.2.146
Published online: January 20, 2016

1Department of Internal Medicine, Gyeongsang National University Hospital, Jinju-si, Gyeongsangnam-do, Korea

2Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju-si, Gyeongsangnam-do, Korea

Corresponding Author: Hahm, Jong Ryeal, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, 79, Gangnam-ro, Jinju-si, Gyeongsangnam-do 52727, Korea Tel: +82-55-750-8736 Fax: +82-55-758-9122 E-mail: jrhahm@gnu.ac.kr
• Received: July 10, 2015   • Accepted: September 16, 2015

Copyright © 2016 Kosin University School of Medicine Proceedings

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Objectives
    To evaluate the efficacy and predictive factors of Dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes mellitus (T2DM) patients who were not well controlled with other oral antidiabetic drugs or insulin in real clinical practice.
  • Methods
    From December 2012 to January 2014, retrospective longitudinal observation study was conducted for patients with T2DM who were not reached a glycemic target (glycated hemoglobin [HbA1c] > 6.5%) with other oral antidiabetic drugs or insulins. Type 1 diabetes or other types of diabetes were excluded. Responders were eligible with decreased HbA1c from baseline for more than 5% during follow up period.
  • Results
    Of total 135 T2DM patients having an average 9.0 months follow-up period, 84 (62.2%) of patients were responder to DPP-4 inhibitors. After concomitant treatment with DPP-4 inhibitors, patients had a mean decrease in HbA1c of 0.69 ± 1.3%, fasting plasma glucose of 13 ± 52 ㎎/㎗, and postprandial plasma glucose of 29 ± 85 ㎎/㎗ from baseline (all P< 0.05). Independent predictive factor for an improvement of glycemic control with DPP-4 inhibitors was higher baseline HbA1c (odds ratio 2.07 with 95% confidence interval 1.15–3.72) compared with non-responders.
  • Conclusions
    A clinical meaningful improvement in glycemic control was seen when DPP-4 inhibitors were added to other anti-diabetic medications in patients with T2DM regardless of age, duration of T2DM, type of combination treatment regimen. Patients who had higher HbA1c were more easily respond to DPP-4 inhibitors treatment in short-term follow-up period.
  • Keywords: Dipeptidyl peptidase-4 inhibitor; efficacy; predictive factor; type 2 diabetes mellitus
Fig. 1.
The efficacy of glycemic control after add-on treatment with DPP-4 inhibitors stratified by concomitant combination treatment. Values in the box represent the mean HbA1c level. ∗ P – value < 0.005 by paired t-test.
kmj-31-146f1.jpg
Table 1.
Baseline characteristics of the study subjects and changes of glycemic control after add-on reatment with DPP-4 inhibitors (N=135)
Parameters n Baseline Follow-up P – value†
Age (years) 135 56.9 (10.0)    
Sex (M, %) 135 82 (60.7)    
BMI (kg/m2) 135 25.1 (3.3)    
SBP (mmHg) 131 125 (15)    
DBP (mmHg) 130 72 (10)    
Duration of diabetes (years) 135 8.6 (7.3)    
Laboratory findings        
FPG (mg/dl) 105 148 (42) 134 (41) 0.019
PP1 (mg/dl) 111 247 (72) 218 (68) 0.002
HbA1c (%) 135 8.1 (1.2) 7.4 (1.3) < 0.001
C-peptide (ng/ml) ∗ 118 2.20 (1.62–2.98) 2.09 (1.59–3.03) 0.423
Total cholesterol (mg/dl) 133 183 (43) 157 (31) < 0.001
Triglyceride (mg/dl) 133 154 (93) 135 (69) 0.014
HDL (mg/dl) 133 48 (22) 47 (14) 0.864
LDL (mg/dl) 133 105 (34) 90 (28) < 0.001
Creatinine (mg/dl) ∗ 132 0.80 (0.69–0.95) 0.82 (0.68–0.96) 0.406
uACR (ug/mg) ∗ 128 16.3 (4.4–51.3) 19.7 (9.4–58.3) 0.765
HOMA2-IR 95 2.07 (1.16) 2.00 (1.16) 0.962
HOMA2%B 95 68.49 (43.30) 70.72 (31.81) 0.323
Combination therapy        
Biguanide (n, %) 135 123 (91.1)    
Sulfonylurea (n, %) 135 72 (53.3)    
TZD (n, %) 135 14 (10.4)    
AGI (n, %) 135 18 (13.3)    
Insulin (n, %) 135 22 (16.3)    
Diabetes-related complications        
Retinopathy (n, %) 135 42 (31.1)    
Nephropathy (n, %) 132 18 (13.6)    
Neuropathy (n, %) 135 34 (25.2)    

Values represent the mean (SD) or number (percentage).

∗ values represent the median (interquartile range)

† analyzed by the paired t-test for normally distributed variables, and by the Wilcoxon signed rank test for continuous variables with skewed distributions.

BMI, body mass index; FPG, fasting plasma glucose; PP1, post-prandial 1-hr glucose; HbA1c, glycated hemoglobin;SBP, systolic blood pressure; DBP, diastolic blood pressure; HDL, high-density lipoprotein; LDL, low-density lipoprotein; uACR, spot urine albumin/creatinine ratio; TZD, thiazolidinedione; AGI, alpha-glucosidase inhibitor; HOMA2%B, homeostasis model assessment of pancreatic beta-cell function; HOMA2-IR, homeostasis model assessment of insulin resistance.

Table 2.
Baseline characteristics according to therapeutic response of DPP-4 inhibitor
Characteristics Responder Non-responder P – value†
n 84 51
Age (years) 57.1 (10.7) 56.6 (8.9) 0.792
Sex (M/F)      
BMI (kg/m2) 24.9 (3.0) 25.5 (3.8) 0.267
SBP (mmHg) 123 (15) 128 (16) 0.069
DBP (mmHg) 72 (10) 73 (10) 0.640
Duration of diabetes (months) 7.8 (7.2) 9.8 (7.3) 0.118
Follow-up duration (months) 9.2 (1.8) 8.6 (1.9) 0.080
FPG (mg/dl) 154 (41) 137 (41) 0.047
PP1 (mg/dl) 245 (67) 250 (79) 0.700
HbA1c (%) 8.4 (1.2) 7.7 (0.9) 0.001
C-peptide (ng/ml) ∗ 2.33 (1.71–3.11) 2.11 (1.54–2.73) 0.172
Total cholesterol (mg/dl) 177 (39) 194 (47) 0.028
TG (mg/dl) 155 (92) 152 (95) 0.816
HDL (mg/dl) 46 (21) 51 (23) 0.259
LDL (mg/dl) 101 (35) 112 (34) 0.073
Creatinine (mg/dl) ∗ 0.81 (0.70–0.96) 0.78 (0.65–0.95) 0.112
HOMA2%B 66.15 (48.12) 72.69 (33.20) 0.437
HOMA2-IR 2.18 (1.27) 1.88 (0.90) 0.177
Combination therapy      
Metformin (n, %) 76 (90.5) 47 (92.2) > 0.999
Sulfonylurea (n, %) 41 (48.8) 31 (60.8) 0.214
TZD (n, %) 11 (13.1) 3 (5.9) 0.249
AGI (n, %) 13 (15.5) 5 (9.8) > 0.999
Insulin (n, %) 8 (9.5) 14 (27.5) 0.008

Values represent the mean (SD) or number (percentage).

∗ values represent the median (interquartile range).

† analyzed by the two-sample t-test for normally distributed variables, and by the Mann Whitney U-test for continuous variables with skewed distributions.

BMI, body mass index;SBP, systolic blood pressure; DBP, diastolic blood pressure; FPG, fasting plasma glucose; PP1, postprandial 1-hr glucose; HbA1c, glycated hemoglobin; TG, triglyceride; HDL, high-dense lipoprotein, HOMA2%B, homeostasis model assessment of pancreatic beta-cell function; HOMA2-IR, homeostasis model assessment of insulin resistance; TZD, thiazolidinedione; AGI, alpha-glucosidase inhibitor.

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        Predictive Factors for the Therapeutic Response to Concomitant Treatment with DPP-4 Inhibitors in Type 2 Diabetes with Short-Term Follow-Up
        Kosin Med J. 2016;31(2):146-156.   Published online January 20, 2016
        DOI: https://doi.org/10.7180/kmj.2016.31.2.146
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