Factors Influencing Glycemic Control Response of Sitagliptin

Gun Woo Kim; Jae Hyun Kim; Mi Young Lee; Jang Yel Shin; Young Goo Shin; Eun Ho Ha; Choon Hee Chung

doi:10.4093/jkd.2013.14.4.206

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Kim, Kim, Lee, Shin, Shin, Ha, and Chung: Factors Influencing Glycemic Control Response of Sitagliptin

Original Articles & Case Reports

J Korean Diabetes 2013;14(4):206-211.

Published online: 10 January 2013

DOI: https://doi.org/10.4093/jkd.2013.14.4.206

Factors Influencing Glycemic Control Response of Sitagliptin

Gun Woo Kim¹, Jae Hyun Kim¹, Mi Young Lee¹, Jang Yel Shin¹, Young Goo Shin¹, Eun Ho Ha², Choon Hee Chung¹

¹Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea

²Department of Information & Statistics, Yonsei University College of Science of Technology, Wonju, Korea

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.

Abstract

Background

Dipeptidyl peptidase 4 (DPP-4) inhibitors are proposed to reduce blood glucose in type 2 diabetes by prolonging the activity of circulating incretins. However, the factors that affect the efficacy of sitagliptin have not yet been demonstrated. Therefore, we studied them in a Korean population.

Methods

We performed a retrospective analysis in patients taking sitagliptin in Wonju Christian Hospital. One hundred-fifty patients whose serum HbA1c ranged from 6.5% to 11% participated in this study. These patients were divided into two groups: responder and non-responder. The responder group consisted of subjects with glucose lowering greater than 5% of baseline HbA1c. The others were in non-responder group. We analyzed anthropometric data and biochemical markers in all groups, then compared responder group and nonresponder group by logistic regression.

Results

The change in HbA1c level across all groups was 8.25 ± 0.82% to 7.64 ± 1.03% (P value = 0.000). There were 93 and 57 patients in responder and non-responder group, respectively. The responder group had lower BMI, body fat (kg), body fat (%) than the non-responder group (P value = 0.024, P value = 0.029, P value = 0.025), and the HbA1c lowering effect of sitagliptin was greater in male than female (P value = 0.000).

Conclusion

In this study, HbA1c was effectively lowered in 62% of the patients. The factors that affect the efficacy of sitagliptin were BMI, body fat (kg) body fat (%), and sex. Based on these results, we conclude that sitagliptin lowers glucose more effectively in non-obese male patients. (J Korean Diabetes 2013;14:206–211)

Keywords: Dipeptidyl-peptidase IV inhibitors, Sitagliptin, Type 2 diabetes mellitus

References

1. King H, Aubert RE, Herman WH. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998; 21:1414–31.

2. Park IB. New and emerging drugs in type 2 diabetes. Korean J Med. 2007; 72:446–50.

3. Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006; 368:1696–705.

4. Drucker DJ. Dipeptidyl peptidase-4 inhibition and the treatment of type 2 diabetes: preclinical biology and mechanisms of action. Diabetes Care. 2007; 30:1335–43.

5. Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and metaanalysis. JAMA. 2007; 298:194–206.

6. Ahrén B. Dipeptidyl peptidase-4 inhibitors: clinical data and clinical implications. Diabetes Care. 2007; 30:1344–50.

7. Kim D, Wang L, Beconi M, Eiermann GJ, Fisher MH, He H, Hickey GJ, Kowalchick JE, Leiting B, Lyons K, Marsilio F, McCann ME, Patel RA, Petrov A, Scapin G, Patel SB, Roy RS, Wu JK, Wyvratt MJ, Zhang BB, Zhu L, Thornberry NA, Weber AE. (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a] pyrazin-7 (8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem. 2005; 48:141–51.

8. Herman GA, Stevens C, Van Dyck K, Bergman A, Yi B, De Smet M, Snyder K, Hilliard D, Tanen M, Tanaka W, Wang AQ, Zeng W, Musson D, Winchell G, Davies MJ, Ramael S, Gottesdiener KM, Wagner JA. Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clin Pharmacol Ther. 2005; 78:675–88.

9. Fehmann HC, Bode HP, Ebert T, Karl A, Göke B. Interaction of GLP-I and leptin at rat pancreatic B-cells: effects on insulin secretion and signal transduction. Horm Metab Res. 1997; 29:572–6.

10. Kim SA, Shim WH, Lee EH, Lee YM, Beom SH, Kim ES, Yoo JS, Nam JS, Cho MH, Park JS, Ahn CW, Kim KR. Predictive clinical parameters for the therapeutic efficacy of sitagliptin in korean type 2 diabetes mellitus. Diabetes Metab J. 2011; 35:159–65.

11. Bergenstal RM, Garrison LP Jr, Miller LA, Hou L, Blickensderfer A, Zagar A, Stanley S, Bhargava A, Wade R, Herman WH. Exenatide BID Observational Study (ExOS): results for primary and secondary endpoints of a prospective research study to evaluate the clinical effectiveness of exenatide BID use in patients with type 2 diabetes in a real-world setting. Curr Med Res Opin. 2011; 27:2335–42.

12. Halimi S, Le Berre MA, Grangé V. Efficacy and safety of acarbose add-on therapy in the treatment of overweight patients with Type 2 diabetes inadequately controlled with metformin: a double-blind, placebo-controlled study. Diabetes Res Clin Pract. 2000; 50:49–56.

13. Seck TL, Engel SS, Williams-Herman DE, Sisk CM, Golm GT, Wang H, Kaufman KD, Goldstein BJ. Sitagliptin more effectively achieves a composite endpoint for A1C reduction, lack of hypoglycemia and no body weight gain compared with glipizide. Diabetes Res Clin Pract. 2011; 93:e15–7.

14. Phillips P, Karrasch J, Scott R, Wilson D, Moses R. Acarbose improves glycemic control in overweight type 2 diabetic patients insufficiently treated with metformin. Diabetes Care. 2003; 26:269–73.

Table 1.

The baseline clinical characteristics of patients

	Male	Female
No. (%)	78 (52)	72 (48)
Age (yr)^a	58.8 ± 9.2	63.1 ± 9.8
Duration of diabetes (yr)^b	10.0 ± 7.3	10.0 ± 8.0
BMI (kg/m²)^a	25.4 ± 2.2	25.1 ± 2.9
Muscle mass (kg)^a	48.5 ± 3.9	35.7 ± 3.9
Body fat (kg)^a	17.3 ± 4.4	19.4 ± 4.4
Body fat (%)^a	24.4 ± 4.2	32.9 ± 4.0
Waist circumference (cm)^a	90.2 ± 6.3	86.6 ± 6.7
Waist-hip ratio^a BMI. body mass index.	0.94 ± 0.04	0.85 ± 0.04

BMI. body mass index.

^a Values are presented as mean ± SD.

^b Values are presented as median ± interquartile range.

Table 2.

The laboratory characteristics of patients

	Male	Female
KITT (%)^a	2.4 ± 1.3	2.7 ± 1.1
HOMA-IR^a	3.1 ± 4.0	3.5 ± 3.1
HOMA-βb	18.3 ± 32	27.3 ± 26.6
Basal serum lab before OGTT
Fasting glucose (mg/dL)^b	177 ± 52	174 ± 62
Insulin (mIU/L)^a	7.5 ± 4.8	8.9 ± 4.9
C-peptide (ng/mL)^a	1.7 ± 0.8	2.0 ± 0.9
Serum lab after 2 hr OGTT
Glucose (mg/dL)^b	363 ± 110	383 ± 159
Insulin (mIU/L)^b	21.6 ± 21.2	36.2 ± 46.2
C-peptide (ng/mL)^b	3.8 ± 2.6	5.1 ± 5.2

KITT, insulin sensitivity test by rate constant for plasma glucose disapperance; HOMA-IR, homeostasis model assessment-insulin resistance; HOMA-β, homeostasis model assessment-β; OGTT, oral glucose tolerance test.

^a Values are presented as mean ± SD.

^b Values are presented as median ± interquartile range.

Table 3.

The change of HbA1C according to the duration of diabetes and FBS levels after sitagliptin treatment

	Patient no.	Before treatment	After treatment	Reduction	P value
HbA1c (%)		8.25 ± 0.82	7.64 ± 1.03		0.000
1–5 yr	30	8.25 ± 0.96	7.32 ± 0.94	0.93 ± 1.14
6–9 yr	43	8.10 ± 0.68	7.70 ± 1.04	0.40 ± 0.84
10 yr-	77	8.33 ± 0.83	7.73 ± 1.04	0.59 ± 0.93
FBS (mg/dL)		158.1 ± 47.4	146.1 ± 41.0		0.005

FBS, fasting blood sugar.

Table 4.

The basal clinical characteristics of responder and non-responder

	Responder	Non-responder	P value
Sex (M/F)	93 (57/36)	57 (21/36)	0.000
Age (yr)	60.8 ± 9.4	61.0 ± 10.2	NS
Duration of diabetes (yr)	10.7 ± 6.3	10.3 ± 5.7	NS
BMI (kg/m²)	24.9 ± 2.5	25.7 ± 2.7	0.024
Muscle mass (kg)	43.1 ± 7.5	41.0 ± 7.5	NS
Body fat (kg)	17.5 ± 4.4	19.5 ± 4.5	0.029
Body fat (%)	27.2 ± 5.8	30.6 ± 5.6	0.025
Waist circumference (cm)	88.2 ± 6.9	88.9 ± 6.5	NS
Waist-hip ratio	0.91 ± 0.01	0.90 ± 0.01	NS

BMI, body mass index; NS, not statistically significant at significance level 0.05.

Table 5.

The differences of clinical parameters between responder and non-responder

	Responder	Non-Responder	P value
KITT (%)	2.5 ± 1.2	2.6 ± 1.2	NS
FBS (mg/dL)	161.7 ± 49.3	152.1 ± 43.8	NS
Insulin (basal) (mIU/L)	5.2 ± 5.0	7.6 ± 4.7	NS
Insulin (2 hr after OGTT) (mIU/L)	31.7 ± 24.6	28.8 ± 18.3	NS
C-peptide (basal) (ng/mL)	1.8 ± 0.9	1.9 ± 0.6	NS
C-peptide (2 hr after OGTT) (ng/mL)	4.9 ± 3.0	5.4 ± 3.0	NS
HOMA-IR	8.2 ± 5.0	7.6 ± 4.7	NS
HOMA-β	26.9 ± 20.8	22.7 ± 12.6	NS

FBS, fasting blood sugar; HOMA-β, homeostasis model assessment-β; HOMA-IR. homeostasis model assessment-insulin resistance; KITT, insulin sensitivity test by rate constant for plasma glucose disappearance; NS, not statistically significant at significance level 0.05.

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