Skip to main content
Top
Published in: Diabetology & Metabolic Syndrome 1/2018

Open Access 01-12-2018 | Research

Coadministration of DPP-4 inhibitor and insulin therapy does not further reduce the risk of cardiovascular events compared with DPP-4 inhibitor therapy in diabetic foot patients: a nationwide population-based study

Authors: Yi-Hsuan Lin, Yu-Yao Huang, Yi-Ling Wu, Cheng-Wei Lin, Pei-Chun Chen, Chee Jen Chang, Sheng-Hwu Hsieh, Jui-Hung Sun, Szu-Tah Chen, Chia-Hung Lin

Published in: Diabetology & Metabolic Syndrome | Issue 1/2018

Login to get access

Abstract

Background

The effect of combined insulin and dipeptidyl peptidase-4 inhibitor (DPP4i) therapy on major adverse cardiovascular events (MACEs) in patients with diabetic foot is unclear.

Methods

We conducted this nationwide cohort study using longitudinal claims data obtained from the Taiwan National Health Insurance program and included 19,791 patients with diabetic foot from 2007 to 2014. Patients receiving DPP4i-based therapy and/or insulin-based therapy after a diagnosis of diabetic foot were categorized into combined, DPP4i- or insulin-based groups, respectively. The risk of MACEs including nonfatal myocardial infarction, nonfatal stroke, cardiac death, and heart failure was assessed using Cox proportional hazards analysis and propensity score matching.

Results

Among the 19,791 patients with diabetic foot (mean age, 58.8 years [SD, 12.5]; men, 51.2%), 6466 received DPP4i-based therapy, 1925 received insulin-based therapy, and 11,400 received combined DPP4i and insulin therapy. The DPP4i-based and insulin-based groups had a lower risk of MACEs (HR 0.53, 95% CI 0.50–0.57 DPP4i only; HR 0.89, 95% CI 0.81–0.97 insulin only) than the combined group. After propensity score matching, the incidence of all complications in the DPP4i-based group was still significantly lower than that in the combined group (HR 0.55, 95% CI 0.51–0.59 for MACEs; HR 0.32, 95% CI 0.24–0.42 for nonfatal myocardial infarction; HR 0.70, 95% CI 0.63–0.78 for nonfatal stroke; HR 0.22, 95% CI 0.13–0.38 for cardiac death; HR 0.22, 95% CI 0.19–0.25 for any death; HR 0.16, 95% CI 0.13–0.20 for amputation). In the diabetic foot patients with end-stage renal disease (ESRD), the benefit of a lower incidence of MACEs in the DPP4i-based group disappeared (HR 0.77, 95% CI 0.58–1.08).

Conclusions

This study demonstrated that the patients with diabetic foot receiving DPP4i-based therapy had a lower risk of MACEs than those receiving combined therapy with DPP4i and insulin, but that the effect disappeared in those with concurrent ESRD.
Appendix
Available only for authorised users
Literature
2.
go back to reference Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA. 2005;293:217–28.CrossRef Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA. 2005;293:217–28.CrossRef
3.
go back to reference Barshes NR, Flores E, Belkin M, Kougias P, Armstrong DG, Mills JL Sr. The accuracy and cost-effectiveness of strategies used to identify peripheral artery disease among patients with diabetic foot ulcers. J Vasc Surg. 2016;64:1682.e3–1690.e3.CrossRef Barshes NR, Flores E, Belkin M, Kougias P, Armstrong DG, Mills JL Sr. The accuracy and cost-effectiveness of strategies used to identify peripheral artery disease among patients with diabetic foot ulcers. J Vasc Surg. 2016;64:1682.e3–1690.e3.CrossRef
4.
go back to reference Huang YY, Lin KD, Jiang YD, Chang CH, Chung CH, Chuang LM, et al. Diabetes-related kidney, eye, and foot disease in Taiwan: an analysis of the nationwide data for 2000–2009. J Formos Med Assoc. 2012;111:637–44.CrossRef Huang YY, Lin KD, Jiang YD, Chang CH, Chung CH, Chuang LM, et al. Diabetes-related kidney, eye, and foot disease in Taiwan: an analysis of the nationwide data for 2000–2009. J Formos Med Assoc. 2012;111:637–44.CrossRef
5.
go back to reference Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ (Clin Res ed). 2000;321:405–12.CrossRef Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ (Clin Res ed). 2000;321:405–12.CrossRef
6.
go back to reference Group TAC. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560–72.CrossRef Group TAC. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560–72.CrossRef
7.
go back to reference Origin Trial I, Gerstein H, Yusuf S, Riddle MC, Ryden L, Bosch J. Rationale, design, and baseline characteristics for a large international trial of cardiovascular disease prevention in people with dysglycemia: the ORIGIN Trial (Outcome Reduction with an Initial Glargine Intervention). Am Heart J. 2008;155(26–32):e1–6. Origin Trial I, Gerstein H, Yusuf S, Riddle MC, Ryden L, Bosch J. Rationale, design, and baseline characteristics for a large international trial of cardiovascular disease prevention in people with dysglycemia: the ORIGIN Trial (Outcome Reduction with an Initial Glargine Intervention). Am Heart J. 2008;155(26–32):e1–6.
8.
go back to reference Monnier L, Hanefeld M, Schnell O, Colette C, Owens D. Insulin and atherosclerosis: how are they related? Diabetes Metab. 2013;39:111–7.CrossRef Monnier L, Hanefeld M, Schnell O, Colette C, Owens D. Insulin and atherosclerosis: how are they related? Diabetes Metab. 2013;39:111–7.CrossRef
9.
go back to reference Dosluoglu HH, Lall P, Nader ND, Harris LM, Dryjski ML. Insulin use is associated with poor limb salvage and survival in diabetic patients with chronic limb ischemia. J Vasc Surg. 2010;51:1178–89 (discussion 88–9).CrossRef Dosluoglu HH, Lall P, Nader ND, Harris LM, Dryjski ML. Insulin use is associated with poor limb salvage and survival in diabetic patients with chronic limb ischemia. J Vasc Surg. 2010;51:1178–89 (discussion 88–9).CrossRef
10.
go back to reference Marso SP, McGuire DK, Zinman B, Poulter NR, Emerson SS, Pieber TR, et al. Efficacy and safety of degludec versus glargine in type 2 diabetes. N Engl J Med. 2017;377:723–32.CrossRef Marso SP, McGuire DK, Zinman B, Poulter NR, Emerson SS, Pieber TR, et al. Efficacy and safety of degludec versus glargine in type 2 diabetes. N Engl J Med. 2017;377:723–32.CrossRef
11.
go back to reference Salazar JJ, Ennis WJ, Koh TJ. Diabetes medications: impact on inflammation and wound healing. J Diabetes Complications. 2016;30:746–52.CrossRef Salazar JJ, Ennis WJ, Koh TJ. Diabetes medications: impact on inflammation and wound healing. J Diabetes Complications. 2016;30:746–52.CrossRef
12.
go back to reference Ferrannini E, DeFronzo RA. Impact of glucose-lowering drugs on cardiovascular disease in type 2 diabetes. Eur Heart J. 2015;36:2288–96.CrossRef Ferrannini E, DeFronzo RA. Impact of glucose-lowering drugs on cardiovascular disease in type 2 diabetes. Eur Heart J. 2015;36:2288–96.CrossRef
13.
go back to reference Fadini GP, Boscaro E, Albiero M, Menegazzo L, Frison V, de Kreutzenberg S, et al. The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes: possible role of stromal-derived factor-1alpha. Diabetes Care. 2010;33:1607–9.CrossRef Fadini GP, Boscaro E, Albiero M, Menegazzo L, Frison V, de Kreutzenberg S, et al. The oral dipeptidyl peptidase-4 inhibitor sitagliptin increases circulating endothelial progenitor cells in patients with type 2 diabetes: possible role of stromal-derived factor-1alpha. Diabetes Care. 2010;33:1607–9.CrossRef
14.
go back to reference Kawanami D, Matoba K, Sango K, Utsunomiya K. Incretin-based therapies for diabetic complications: basic mechanisms and clinical evidence. Int J Mol Sci. 2016;17:1223.CrossRef Kawanami D, Matoba K, Sango K, Utsunomiya K. Incretin-based therapies for diabetic complications: basic mechanisms and clinical evidence. Int J Mol Sci. 2016;17:1223.CrossRef
15.
go back to reference Son JW, Kim S. Dipeptidyl peptidase 4 inhibitors and the risk of cardiovascular disease in patients with type 2 diabetes: a tale of three studies. Diabetes Metab J. 2015;39:373–83.CrossRef Son JW, Kim S. Dipeptidyl peptidase 4 inhibitors and the risk of cardiovascular disease in patients with type 2 diabetes: a tale of three studies. Diabetes Metab J. 2015;39:373–83.CrossRef
16.
go back to reference Chen C, Yu Q, Zhang S, Yang P, Wang CY. Assessing the efficacy and safety of combined DPP-4 inhibitor and insulin treatment in patients with type 2 diabetes: a meta-analysis. Int J Clin Exp Pathol. 2015;8:14141–50.PubMedPubMedCentral Chen C, Yu Q, Zhang S, Yang P, Wang CY. Assessing the efficacy and safety of combined DPP-4 inhibitor and insulin treatment in patients with type 2 diabetes: a meta-analysis. Int J Clin Exp Pathol. 2015;8:14141–50.PubMedPubMedCentral
17.
go back to reference Hollander P, Raslova K, Skjoth TV, Rastam J, Liutkus JF. Efficacy and safety of insulin detemir once daily in combination with sitagliptin and metformin: the TRANSITION randomized controlled trial. Diabetes Obes Metab. 2011;13:268–75.CrossRef Hollander P, Raslova K, Skjoth TV, Rastam J, Liutkus JF. Efficacy and safety of insulin detemir once daily in combination with sitagliptin and metformin: the TRANSITION randomized controlled trial. Diabetes Obes Metab. 2011;13:268–75.CrossRef
18.
go back to reference Barnett AH, Charbonnel B, Li J, Donovan M, Fleming D, Iqbal N. Saxagliptin add-on therapy to insulin with or without metformin for type 2 diabetes mellitus: 52-week safety and efficacy. Clin Drug Investig. 2013;33:707–17.CrossRef Barnett AH, Charbonnel B, Li J, Donovan M, Fleming D, Iqbal N. Saxagliptin add-on therapy to insulin with or without metformin for type 2 diabetes mellitus: 52-week safety and efficacy. Clin Drug Investig. 2013;33:707–17.CrossRef
19.
go back to reference Vilsboll T, Rosenstock J, Yki-Jarvinen H, Cefalu WT, Chen Y, Luo E, et al. Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes. Diabetes Obes Metab. 2010;12:167–77.CrossRef Vilsboll T, Rosenstock J, Yki-Jarvinen H, Cefalu WT, Chen Y, Luo E, et al. Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes. Diabetes Obes Metab. 2010;12:167–77.CrossRef
20.
go back to reference Zhang Y, Hong J, Chi J, Gu W, Ning G, Wang W. Head-to-head comparison of dipeptidyl peptidase-IV inhibitors and sulfonylureas—a meta-analysis from randomized clinical trials. Diabetes Metab Res Rev. 2014;30:241–56.CrossRef Zhang Y, Hong J, Chi J, Gu W, Ning G, Wang W. Head-to-head comparison of dipeptidyl peptidase-IV inhibitors and sulfonylureas—a meta-analysis from randomized clinical trials. Diabetes Metab Res Rev. 2014;30:241–56.CrossRef
21.
go back to reference Bae EJ. DPP-4 inhibitors in diabetic complications: role of DPP-4 beyond glucose control. Arch Pharm Res. 2016;39:1114–28.CrossRef Bae EJ. DPP-4 inhibitors in diabetic complications: role of DPP-4 beyond glucose control. Arch Pharm Res. 2016;39:1114–28.CrossRef
22.
go back to reference Yang TY, Liaw YP, Huang JY, Chang HR, Chang KW, Ueng KC. Association of Sitagliptin with cardiovascular outcome in diabetic patients: a nationwide cohort study. Acta Diabetol. 2016;53:461–8.CrossRef Yang TY, Liaw YP, Huang JY, Chang HR, Chang KW, Ueng KC. Association of Sitagliptin with cardiovascular outcome in diabetic patients: a nationwide cohort study. Acta Diabetol. 2016;53:461–8.CrossRef
23.
go back to reference Wu B, Bell K, Stanford A, Kern DM, Tunceli O, Vupputuri S, et al. Understanding CKD among patients with T2DM: prevalence, temporal trends, and treatment patterns-NHANES 2007–2012. BMJ Open Diabetes Res Care. 2016;4:e000154.CrossRef Wu B, Bell K, Stanford A, Kern DM, Tunceli O, Vupputuri S, et al. Understanding CKD among patients with T2DM: prevalence, temporal trends, and treatment patterns-NHANES 2007–2012. BMJ Open Diabetes Res Care. 2016;4:e000154.CrossRef
24.
go back to reference El Sharaawy AEB, Ezzat H, Mohab A, Elwasly D. Association between renal function and diabetic foot ulcer in type 2 diabetic patients. Int J Adv Res Biol Sci. 2017;4:7–15.CrossRef El Sharaawy AEB, Ezzat H, Mohab A, Elwasly D. Association between renal function and diabetic foot ulcer in type 2 diabetic patients. Int J Adv Res Biol Sci. 2017;4:7–15.CrossRef
25.
go back to reference Knezevich E, Kueser A. Utility of antidiabetes medications in chronic kidney disease: a review. J Diabetes Nurs. 2016;20:358–63. Knezevich E, Kueser A. Utility of antidiabetes medications in chronic kidney disease: a review. J Diabetes Nurs. 2016;20:358–63.
27.
go back to reference Terry T, Raravikar K, Chokrungvaranon N, Reaven PD. Does aggressive glycemic control benefit macrovascular and microvascular disease in type 2 diabetes? Insights from ACCORD, ADVANCE, and VADT. Curr Cardiol Rep. 2012;14:79–88.CrossRef Terry T, Raravikar K, Chokrungvaranon N, Reaven PD. Does aggressive glycemic control benefit macrovascular and microvascular disease in type 2 diabetes? Insights from ACCORD, ADVANCE, and VADT. Curr Cardiol Rep. 2012;14:79–88.CrossRef
28.
go back to reference Scheen AJ. DPP-4 inhibitors in the management of type 2 diabetes: a critical review of head-to-head trials. Diabetes Metab. 2012;38:89–101.CrossRef Scheen AJ. DPP-4 inhibitors in the management of type 2 diabetes: a critical review of head-to-head trials. Diabetes Metab. 2012;38:89–101.CrossRef
29.
go back to reference Tuttolomondo A, Maida C, Pinto A. Diabetic foot syndrome: immune-inflammatory features as possible cardiovascular markers in diabetes. World J Orthop. 2015;6:62–76.CrossRef Tuttolomondo A, Maida C, Pinto A. Diabetic foot syndrome: immune-inflammatory features as possible cardiovascular markers in diabetes. World J Orthop. 2015;6:62–76.CrossRef
30.
go back to reference Tuttolomondo A, Maida C, Pinto A. Diabetic foot syndrome as a possible cardiovascular marker in diabetic patients. J Diabetes Res. 2015;2015:268390.CrossRef Tuttolomondo A, Maida C, Pinto A. Diabetic foot syndrome as a possible cardiovascular marker in diabetic patients. J Diabetes Res. 2015;2015:268390.CrossRef
31.
go back to reference Romacho T, Vallejo S, Villalobos LA, Wronkowitz N, Indrakusuma I, Sell H, et al. Soluble dipeptidyl peptidase-4 induces microvascular endothelial dysfunction through proteinase-activated receptor-2 and thromboxane A2 release. J Hypertens. 2016;34:869–76.CrossRef Romacho T, Vallejo S, Villalobos LA, Wronkowitz N, Indrakusuma I, Sell H, et al. Soluble dipeptidyl peptidase-4 induces microvascular endothelial dysfunction through proteinase-activated receptor-2 and thromboxane A2 release. J Hypertens. 2016;34:869–76.CrossRef
32.
go back to reference Mita T, Katakami N, Shiraiwa T, Yoshii H, Gosho M, Shimomura I, et al. The effect of sitagliptin on the regression of carotid intima-media thickening in patients with type 2 diabetes mellitus: a post hoc analysis of the sitagliptin preventive study of intima-media thickness evaluation. Int J Endocrinol. 2017;2017:1925305.CrossRef Mita T, Katakami N, Shiraiwa T, Yoshii H, Gosho M, Shimomura I, et al. The effect of sitagliptin on the regression of carotid intima-media thickening in patients with type 2 diabetes mellitus: a post hoc analysis of the sitagliptin preventive study of intima-media thickness evaluation. Int J Endocrinol. 2017;2017:1925305.CrossRef
33.
go back to reference Scheen AJ. Cardiovascular outcome studies with incretin-based therapies: comparison between DPP-4 inhibitors and GLP-1 receptor agonists. Diabetes Res Clin Pract. 2017;127:224–37.CrossRef Scheen AJ. Cardiovascular outcome studies with incretin-based therapies: comparison between DPP-4 inhibitors and GLP-1 receptor agonists. Diabetes Res Clin Pract. 2017;127:224–37.CrossRef
34.
go back to reference Weng J, Li Y, Xu W, Shi L, Zhang Q, Zhu D, et al. Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial. Lancet (London, England). 2008;371:1753–60.CrossRef Weng J, Li Y, Xu W, Shi L, Zhang Q, Zhu D, et al. Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial. Lancet (London, England). 2008;371:1753–60.CrossRef
35.
go back to reference Stout RW. The role of insulin in atherosclerosis in diabetics and nondiabetics: a review. Diabetes. 1981;30:54–7.CrossRef Stout RW. The role of insulin in atherosclerosis in diabetics and nondiabetics: a review. Diabetes. 1981;30:54–7.CrossRef
36.
go back to reference Herman ME, O’Keefe JH, Bell DSH, Schwartz SS. Insulin therapy increases cardiovascular risk: time for a sea of change in type 2 diabetes treatment. Progress Cardiovasc Dis. 2017;60:422–34.CrossRef Herman ME, O’Keefe JH, Bell DSH, Schwartz SS. Insulin therapy increases cardiovascular risk: time for a sea of change in type 2 diabetes treatment. Progress Cardiovasc Dis. 2017;60:422–34.CrossRef
37.
go back to reference Jil M, Rajnikant M, Richard D, Iskandar I. The effects of dual-therapy intensification with insulin or dipeptidyl peptidase-4 inhibitor on cardiovascular events and all-cause mortality in patients with type 2 diabetes: a retrospective cohort study. Diabetes Vasc Dis Res. 2017;14:295–303.CrossRef Jil M, Rajnikant M, Richard D, Iskandar I. The effects of dual-therapy intensification with insulin or dipeptidyl peptidase-4 inhibitor on cardiovascular events and all-cause mortality in patients with type 2 diabetes: a retrospective cohort study. Diabetes Vasc Dis Res. 2017;14:295–303.CrossRef
38.
go back to reference Zoccali C, Mallamaci F, Tripepi G. Inflammation and atherosclerosis in end-stage renal disease. Blood Purif. 2003;21:29–36.CrossRef Zoccali C, Mallamaci F, Tripepi G. Inflammation and atherosclerosis in end-stage renal disease. Blood Purif. 2003;21:29–36.CrossRef
39.
go back to reference Guerin AP, London GM, Marchais SJ, Metivier F. Arterial stiffening and vascular calcifications in end-stage renal disease. Nephrol Dial Transplant. 2000;15:1014–21.CrossRef Guerin AP, London GM, Marchais SJ, Metivier F. Arterial stiffening and vascular calcifications in end-stage renal disease. Nephrol Dial Transplant. 2000;15:1014–21.CrossRef
40.
go back to reference London GM, Pannier B, Marchais SJ. Vascular calcifications, arterial aging and arterial remodeling in ESRD. Blood Purif. 2013;35:16–21.CrossRef London GM, Pannier B, Marchais SJ. Vascular calcifications, arterial aging and arterial remodeling in ESRD. Blood Purif. 2013;35:16–21.CrossRef
41.
go back to reference Zubair M. Glycosylated hemoglobin in diabetic foot and its correlation with clinical variables in a north Indian tertiary care hospital. J Diabetes Metab. 2015;6:571.CrossRef Zubair M. Glycosylated hemoglobin in diabetic foot and its correlation with clinical variables in a north Indian tertiary care hospital. J Diabetes Metab. 2015;6:571.CrossRef
42.
go back to reference Aschner P, Sethi B, Gomez-Peralta F, Landgraf W, Loizeau V, Dain M-P, et al. Insulin glargine compared with premixed insulin for management of insulin-naïve type 2 diabetes patients uncontrolled on oral antidiabetic drugs: the open-label, randomized GALAPAGOS study. J Diabetes Complications. 2015;29:838–45.CrossRef Aschner P, Sethi B, Gomez-Peralta F, Landgraf W, Loizeau V, Dain M-P, et al. Insulin glargine compared with premixed insulin for management of insulin-naïve type 2 diabetes patients uncontrolled on oral antidiabetic drugs: the open-label, randomized GALAPAGOS study. J Diabetes Complications. 2015;29:838–45.CrossRef
43.
go back to reference Brownlee M, Hirsch IB. Glycemic variability: a hemoglobin A1c-independent risk factor for diabetic complications. JAMA. 2006;295:1707–8.CrossRef Brownlee M, Hirsch IB. Glycemic variability: a hemoglobin A1c-independent risk factor for diabetic complications. JAMA. 2006;295:1707–8.CrossRef
44.
go back to reference Heine RJ, Balkau B, Ceriello A, Del Prato S, Horton ES, Taskinen MR. What does postprandial hyperglycaemia mean? Diabetic Med. 2004;21:208–13.CrossRef Heine RJ, Balkau B, Ceriello A, Del Prato S, Horton ES, Taskinen MR. What does postprandial hyperglycaemia mean? Diabetic Med. 2004;21:208–13.CrossRef
45.
go back to reference Gomez-Peralta F, Abreu C, Mora-Navarro G, Lopez-Morandeira P, Perez-Gutierrez E, Cordero-Garcia B, et al. Switching from premixed insulin to basal insulin analogue for type 2 diabetes and role of dipeptidyl peptidase-4 inhibitors. Exp Clin Endocrinol Diabetes. 2018;126:268–76.CrossRef Gomez-Peralta F, Abreu C, Mora-Navarro G, Lopez-Morandeira P, Perez-Gutierrez E, Cordero-Garcia B, et al. Switching from premixed insulin to basal insulin analogue for type 2 diabetes and role of dipeptidyl peptidase-4 inhibitors. Exp Clin Endocrinol Diabetes. 2018;126:268–76.CrossRef
46.
go back to reference Marfella R, Sasso FC, Rizzo MR, Paolisso P, Barbieri M, Padovano V, et al. Dipeptidyl peptidase 4 inhibition may facilitate healing of chronic foot ulcers in patients with type 2 diabetes. Exp Diabetes Res. 2012;2012:892706.CrossRef Marfella R, Sasso FC, Rizzo MR, Paolisso P, Barbieri M, Padovano V, et al. Dipeptidyl peptidase 4 inhibition may facilitate healing of chronic foot ulcers in patients with type 2 diabetes. Exp Diabetes Res. 2012;2012:892706.CrossRef
47.
go back to reference Saboo A, Rathnayake A, Vangaveti VN, Malabu UH. Wound healing effects of dipeptidyl peptidase-4 inhibitors: an emerging concept in management of diabetic foot ulcer—a review. Diabetes Metab Syndr. 2016;10:113–9.CrossRef Saboo A, Rathnayake A, Vangaveti VN, Malabu UH. Wound healing effects of dipeptidyl peptidase-4 inhibitors: an emerging concept in management of diabetic foot ulcer—a review. Diabetes Metab Syndr. 2016;10:113–9.CrossRef
48.
go back to reference Long M, Cai L, Li W, Zhang L, Guo S, Zhang R, et al. DPP-4 inhibitors improve diabetic wound healing via direct and indirect promotion of epithelial–mesenchymal transition and reduction of scarring. Diabetes. 2018;67:518–31.CrossRef Long M, Cai L, Li W, Zhang L, Guo S, Zhang R, et al. DPP-4 inhibitors improve diabetic wound healing via direct and indirect promotion of epithelial–mesenchymal transition and reduction of scarring. Diabetes. 2018;67:518–31.CrossRef
Metadata
Title
Coadministration of DPP-4 inhibitor and insulin therapy does not further reduce the risk of cardiovascular events compared with DPP-4 inhibitor therapy in diabetic foot patients: a nationwide population-based study
Authors
Yi-Hsuan Lin
Yu-Yao Huang
Yi-Ling Wu
Cheng-Wei Lin
Pei-Chun Chen
Chee Jen Chang
Sheng-Hwu Hsieh
Jui-Hung Sun
Szu-Tah Chen
Chia-Hung Lin
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Diabetology & Metabolic Syndrome / Issue 1/2018
Electronic ISSN: 1758-5996
DOI
https://doi.org/10.1186/s13098-018-0378-6

Other articles of this Issue 1/2018

Diabetology & Metabolic Syndrome 1/2018 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.