Skip to main content
Top
Published in: Cardiovascular Diabetology 1/2018

Open Access 01-12-2018 | Original investigation

Linagliptin and cardiovascular outcomes in type 2 diabetes after acute coronary syndrome or acute ischemic stroke

Authors: Yan-Rong Li, Sung-Sheng Tsai, Dong-Yi Chen, Szu-Tah Chen, Jui-Hung Sun, Hung-Yu Chang, Miaw-Jene Liou, Tien-Hsing Chen

Published in: Cardiovascular Diabetology | Issue 1/2018

Login to get access

Abstract

Background

The cardiovascular safety and efficacy of linagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus (T2DM) after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) are unclear. The aim of our real-world cohort study was to evaluate the cardiovascular outcomes of linagliptin in patients with T2DM after ACS or AIS.

Methods

An open observational noncrossover retrospective cohort study was conducted between June 1, 2012 and December 31, 2013 utilizing Taiwan National Health Insurance Research Database. A total of 1203 patients with T2DM after ACS or AIS were selected as the study cohort. Cardiovascular safety and efficacy of linagliptin were evaluated by comparing outcomes of 401 subjects receiving linagliptin after ACS or AIS to 802 matched control subjects not receiving any incretin-based therapy after ACS or AIS. The primary composite outcome included cardiovascular death, non-fatal myocardial infarction and non-fatal ischemic stroke.

Results

The primary composite outcome after 15-month follow-up was 7% (28 patients) in the linagliptin group compared with 6.1% (49 patients) in the control group [hazard ratio (HR) 1.06; 95% confidence interval (CI) .66–1.68]. The linagliptin group also had similar risks of all-cause mortality, hospitalization for heart failure, percutaneous coronary intervention and coronary artery bypass grafting compared to the control group in terms of the secondary outcomes.

Conclusions

In T2DM patients after ACS or AIS, treatment with linagliptin was not associated with increased risks of cardiovascular death, non-fatal myocardial infarction, or non-fatal ischemic stroke.
Literature
1.
go back to reference Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229–34.CrossRefPubMed Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229–34.CrossRefPubMed
2.
go back to reference Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375:2215–22.CrossRefPubMed Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375:2215–22.CrossRefPubMed
3.
go back to reference Preis SR, Hwang SJ, Coady S, Pencina MJ, D’Agostino RB Sr, Savage PJ, et al. Trends in all-cause and cardiovascular disease mortality among women and men with and without diabetes mellitus in the Framingham Heart Study, 1950 to 2005. Circulation. 2009;119:1728–35.CrossRefPubMedPubMedCentral Preis SR, Hwang SJ, Coady S, Pencina MJ, D’Agostino RB Sr, Savage PJ, et al. Trends in all-cause and cardiovascular disease mortality among women and men with and without diabetes mellitus in the Framingham Heart Study, 1950 to 2005. Circulation. 2009;119:1728–35.CrossRefPubMedPubMedCentral
4.
go back to reference Morrish NJ, Wang SL, Stevens LK, Fuller JH, Keen H. Mortality and causes of death in the WHO Multinational Study of Vascular Disease in Diabetes. Diabetologia. 2001;44(Suppl 2):14–21.CrossRef Morrish NJ, Wang SL, Stevens LK, Fuller JH, Keen H. Mortality and causes of death in the WHO Multinational Study of Vascular Disease in Diabetes. Diabetologia. 2001;44(Suppl 2):14–21.CrossRef
5.
go back to reference UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–53.CrossRef UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–53.CrossRef
6.
go back to reference Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545–59.CrossRefPubMed Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545–59.CrossRefPubMed
7.
go back to reference Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560–72.CrossRefPubMed Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560–72.CrossRefPubMed
8.
go back to reference Gerstein HC, Miller ME, Genuth S, Ismail-Beigi F, Buse JB, Goff DC Jr, et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011;364:818–28.CrossRefPubMed Gerstein HC, Miller ME, Genuth S, Ismail-Beigi F, Buse JB, Goff DC Jr, et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011;364:818–28.CrossRefPubMed
9.
go back to reference Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M, et al. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013;369:145–54.CrossRefPubMed Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M, et al. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013;369:145–54.CrossRefPubMed
10.
go back to reference Cavender MA, Steg PG, Smith SC, Eagle K, Ohman EM, Goto S, et al. Impact of diabetes mellitus on hospitalization for heart failure, cardiovascular events, and death: outcomes at 4 years from the reduction of atherothrombosis for continued health (REACH) registry. Circulation. 2015;132:923–31.CrossRefPubMed Cavender MA, Steg PG, Smith SC, Eagle K, Ohman EM, Goto S, et al. Impact of diabetes mellitus on hospitalization for heart failure, cardiovascular events, and death: outcomes at 4 years from the reduction of atherothrombosis for continued health (REACH) registry. Circulation. 2015;132:923–31.CrossRefPubMed
11.
go back to reference Guidance for industry. diabetes mellitus—evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes. Silver Spring: Food and Drug Administration; 2008. Guidance for industry. diabetes mellitus—evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes. Silver Spring: Food and Drug Administration; 2008.
12.
go back to reference Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369:1317–26.CrossRefPubMed Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369:1317–26.CrossRefPubMed
13.
go back to reference White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris GL, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369:1327–35.CrossRefPubMed White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris GL, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369:1327–35.CrossRefPubMed
14.
go back to reference Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;373:232–42.CrossRefPubMed Green JB, Bethel MA, Armstrong PW, Buse JB, Engel SS, Garg J, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;373:232–42.CrossRefPubMed
15.
go back to reference Zannad F, Cannon CP, Cushman WC, Bakris GL, Menon V, Perez AT, et al. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial. Lancet. 2015;385:2067–76.CrossRefPubMed Zannad F, Cannon CP, Cushman WC, Bakris GL, Menon V, Perez AT, et al. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial. Lancet. 2015;385:2067–76.CrossRefPubMed
17.
go back to reference Filion KB, Suissa S. DPP-4 inhibitors and heart failure: some reassurance, some uncertainty. Diabetes Care. 2016;39:735–7.CrossRefPubMed Filion KB, Suissa S. DPP-4 inhibitors and heart failure: some reassurance, some uncertainty. Diabetes Care. 2016;39:735–7.CrossRefPubMed
18.
go back to reference Baetta R, Corsini A. Pharmacology of dipeptidyl peptidase-4 inhibitors: similarities and differences. Drugs. 2011;71:1441–67.CrossRefPubMed Baetta R, Corsini A. Pharmacology of dipeptidyl peptidase-4 inhibitors: similarities and differences. Drugs. 2011;71:1441–67.CrossRefPubMed
19.
go back to reference Deacon CF, Holst JJ. Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor with an unusual profile for the treatment of type 2 diabetes. Expert Opin Investig Drugs. 2010;19:133–40.CrossRefPubMed Deacon CF, Holst JJ. Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor with an unusual profile for the treatment of type 2 diabetes. Expert Opin Investig Drugs. 2010;19:133–40.CrossRefPubMed
20.
go back to reference Graefe-Mody U, Friedrich C, Port A, Ring A, Retlich S, Heise T, et al. Effect of renal impairment on the pharmacokinetics of the dipeptidyl peptidase-4 inhibitor linagliptin. Diabetes Obes Metab. 2011;13:939–46.CrossRefPubMed Graefe-Mody U, Friedrich C, Port A, Ring A, Retlich S, Heise T, et al. Effect of renal impairment on the pharmacokinetics of the dipeptidyl peptidase-4 inhibitor linagliptin. Diabetes Obes Metab. 2011;13:939–46.CrossRefPubMed
21.
go back to reference Boehringer Ingelheim. Cardiovascular and Renal Microvascular Outcome Study With Linagliptin in Patients With Type 2 Diabetes Mellitus (CARMELINA). [ClinicalTrials.gov identifier: NCT01897532]. US National Institutes of Health, ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01897532 Accessed 2017 Oct 4. Boehringer Ingelheim. Cardiovascular and Renal Microvascular Outcome Study With Linagliptin in Patients With Type 2 Diabetes Mellitus (CARMELINA). [ClinicalTrials.gov identifier: NCT01897532]. US National Institutes of Health, ClinicalTrials.gov. https://​clinicaltrials.​gov/​ct2/​show/​NCT01897532 Accessed 2017 Oct 4.
22.
23.
go back to reference McKeage K. Linagliptin: an update of its use in patients with type 2 diabetes mellitus. Drugs. 2014;74:1927–46.CrossRefPubMed McKeage K. Linagliptin: an update of its use in patients with type 2 diabetes mellitus. Drugs. 2014;74:1927–46.CrossRefPubMed
24.
go back to reference Barnett AH. Linagliptin for the treatment of type 2 diabetes mellitus: a drug safety evaluation. Expert Opin Drug Saf. 2015;14:149–59.CrossRefPubMed Barnett AH. Linagliptin for the treatment of type 2 diabetes mellitus: a drug safety evaluation. Expert Opin Drug Saf. 2015;14:149–59.CrossRefPubMed
25.
go back to reference Gallwitz B, Rosenstock J, Rauch T, Bhattacharya S, Patel S, von Eynatten M, et al. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet. 2012;380:475–83.CrossRefPubMed Gallwitz B, Rosenstock J, Rauch T, Bhattacharya S, Patel S, von Eynatten M, et al. 2-year efficacy and safety of linagliptin compared with glimepiride in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, non-inferiority trial. Lancet. 2012;380:475–83.CrossRefPubMed
26.
go back to reference Johansen OE, Neubacher D, von Eynatten M, Patel S, Woerle HJ. Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme. Cardiovasc Diabetol. 2012;11:3.CrossRefPubMedPubMedCentral Johansen OE, Neubacher D, von Eynatten M, Patel S, Woerle HJ. Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme. Cardiovasc Diabetol. 2012;11:3.CrossRefPubMedPubMedCentral
27.
go back to reference Hsieh CY, Chen CH, Li CY, Lai ML. Validating the diagnosis of acute ischemic stroke in a National Health Insurance claims database. J Formos Med Assoc. 2015;114:254–9.CrossRefPubMed Hsieh CY, Chen CH, Li CY, Lai ML. Validating the diagnosis of acute ischemic stroke in a National Health Insurance claims database. J Formos Med Assoc. 2015;114:254–9.CrossRefPubMed
28.
go back to reference Chang CH, Lee YC, Tsai CT, Chang SN, Chung YH, Lin MS, et al. Continuation of statin therapy and a decreased risk of atrial fibrillation/flutter in patients with and without chronic kidney disease. Atherosclerosis. 2014;232:224–30.CrossRefPubMed Chang CH, Lee YC, Tsai CT, Chang SN, Chung YH, Lin MS, et al. Continuation of statin therapy and a decreased risk of atrial fibrillation/flutter in patients with and without chronic kidney disease. Atherosclerosis. 2014;232:224–30.CrossRefPubMed
29.
go back to reference Cheng CL, Lee CH, Chen PS, Li YH, Lin SJ, Yang YH. Validation of acute myocardial infarction cases in the national health insurance research database in taiwan. J Epidemiol. 2014;24:500–7.CrossRefPubMedPubMedCentral Cheng CL, Lee CH, Chen PS, Li YH, Lin SJ, Yang YH. Validation of acute myocardial infarction cases in the national health insurance research database in taiwan. J Epidemiol. 2014;24:500–7.CrossRefPubMedPubMedCentral
30.
go back to reference Cheng CL, Kao YH, Lin SJ, Lee CH, Lai ML. Validation of the National Health Insurance Research Database with ischemic stroke cases in Taiwan. Pharmacoepidemiol Drug Saf. 2011;20:236–42.CrossRefPubMed Cheng CL, Kao YH, Lin SJ, Lee CH, Lai ML. Validation of the National Health Insurance Research Database with ischemic stroke cases in Taiwan. Pharmacoepidemiol Drug Saf. 2011;20:236–42.CrossRefPubMed
31.
go back to reference Hsing AW, Ioannidis JP. Nationwide population science: lessons from the Taiwan National Health Insurance Research Database. JAMA Intern Med. 2015;175:1527–9.CrossRefPubMed Hsing AW, Ioannidis JP. Nationwide population science: lessons from the Taiwan National Health Insurance Research Database. JAMA Intern Med. 2015;175:1527–9.CrossRefPubMed
32.
go back to reference Wu CY, Chen YJ, Ho HJ, Hsu YC, Kuo KN, Wu MS, et al. Association between nucleoside analogues and risk of hepatitis B virus-related hepatocellular carcinoma recurrence following liver resection. JAMA. 2012;308:1906–14.CrossRefPubMed Wu CY, Chen YJ, Ho HJ, Hsu YC, Kuo KN, Wu MS, et al. Association between nucleoside analogues and risk of hepatitis B virus-related hepatocellular carcinoma recurrence following liver resection. JAMA. 2012;308:1906–14.CrossRefPubMed
33.
go back to reference Ou HT, Chang KC, Li CY, Wu JS. Risks of cardiovascular diseases associated with dipeptidyl peptidase-4 inhibitors and other antidiabetic drugs in patients with type 2 diabetes: a nation-wide longitudinal study. Cardiovasc Diabetol. 2016;15:41.CrossRefPubMedPubMedCentral Ou HT, Chang KC, Li CY, Wu JS. Risks of cardiovascular diseases associated with dipeptidyl peptidase-4 inhibitors and other antidiabetic drugs in patients with type 2 diabetes: a nation-wide longitudinal study. Cardiovasc Diabetol. 2016;15:41.CrossRefPubMedPubMedCentral
34.
go back to reference Kim YG, Yoon D, Park S, Han SJ, Kim DJ, Lee KW, et al. Dipeptidyl peptidase-4 inhibitors and risk of heart failure in patients with Type 2 diabetes mellitus: a Population-Based Cohort Study. Circ Heart Fail. 2017;10(9):e003957.CrossRefPubMed Kim YG, Yoon D, Park S, Han SJ, Kim DJ, Lee KW, et al. Dipeptidyl peptidase-4 inhibitors and risk of heart failure in patients with Type 2 diabetes mellitus: a Population-Based Cohort Study. Circ Heart Fail. 2017;10(9):e003957.CrossRefPubMed
35.
go back to reference Lehrke M, Leiter LA, Hehnke U, Thiemann S, Bhandari A, Meinicke T, et al. Safety and efficacy of linagliptin in patients with type 2 diabetes mellitus and coronary artery disease: analysis of pooled events from 19 clinical trials. J Diabetes Complications. 2016;30:1378–84.CrossRefPubMed Lehrke M, Leiter LA, Hehnke U, Thiemann S, Bhandari A, Meinicke T, et al. Safety and efficacy of linagliptin in patients with type 2 diabetes mellitus and coronary artery disease: analysis of pooled events from 19 clinical trials. J Diabetes Complications. 2016;30:1378–84.CrossRefPubMed
36.
go back to reference Zinman B, Ahren B, Neubacher D, Patel S, Woerle HJ, Johansen OE. Efficacy and cardiovascular safety of linagliptin as an add-on to insulin in Type 2 diabetes: a Pooled Comprehensive Post Hoc Analysis. Can J Diabetes. 2016;40:50–7.CrossRefPubMed Zinman B, Ahren B, Neubacher D, Patel S, Woerle HJ, Johansen OE. Efficacy and cardiovascular safety of linagliptin as an add-on to insulin in Type 2 diabetes: a Pooled Comprehensive Post Hoc Analysis. Can J Diabetes. 2016;40:50–7.CrossRefPubMed
37.
go back to reference Rosenstock J, Marx N, Neubacher D, Seck T, Patel S, Woerle HJ, et al. Cardiovascular safety of linagliptin in type 2 diabetes: a comprehensive patient-level pooled analysis of prospectively adjudicated cardiovascular events. Cardiovasc Diabetol. 2015;14:57.CrossRefPubMedPubMedCentral Rosenstock J, Marx N, Neubacher D, Seck T, Patel S, Woerle HJ, et al. Cardiovascular safety of linagliptin in type 2 diabetes: a comprehensive patient-level pooled analysis of prospectively adjudicated cardiovascular events. Cardiovasc Diabetol. 2015;14:57.CrossRefPubMedPubMedCentral
38.
go back to reference Lehrke M, Marx N, Patel S, Seck T, Crowe S, Cheng K, et al. Safety and tolerability of linagliptin in patients with Type 2 diabetes: a Comprehensive Pooled Analysis of 22 Placebo-controlled Studies. Clin Ther. 2014;36:1130–46.CrossRefPubMed Lehrke M, Marx N, Patel S, Seck T, Crowe S, Cheng K, et al. Safety and tolerability of linagliptin in patients with Type 2 diabetes: a Comprehensive Pooled Analysis of 22 Placebo-controlled Studies. Clin Ther. 2014;36:1130–46.CrossRefPubMed
39.
go back to reference Scirica BM, Braunwald E, Raz I, Cavender MA, Morrow DA, Jarolim P, et al. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation. 2014;130:1579–88.CrossRefPubMed Scirica BM, Braunwald E, Raz I, Cavender MA, Morrow DA, Jarolim P, et al. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation. 2014;130:1579–88.CrossRefPubMed
40.
go back to reference Manrique C, Habibi J, Aroor AR, Sowers JR, Jia G, Hayden MR, et al. Dipeptidyl peptidase-4 inhibition with linagliptin prevents western diet-induced vascular abnormalities in female mice. Cardiovasc Diabetol. 2016;15:94.CrossRefPubMedPubMedCentral Manrique C, Habibi J, Aroor AR, Sowers JR, Jia G, Hayden MR, et al. Dipeptidyl peptidase-4 inhibition with linagliptin prevents western diet-induced vascular abnormalities in female mice. Cardiovasc Diabetol. 2016;15:94.CrossRefPubMedPubMedCentral
41.
go back to reference Aroor AR, Habibi J, Kandikattu HK, Garro-Kacher M, Barron B, Chen D, et al. Dipeptidyl peptidase-4 (DPP-4) inhibition with linagliptin reduces western diet-induced myocardial TRAF3IP2 expression, inflammation and fibrosis in female mice. Cardiovasc Diabetol. 2017;16:61.CrossRefPubMedPubMedCentral Aroor AR, Habibi J, Kandikattu HK, Garro-Kacher M, Barron B, Chen D, et al. Dipeptidyl peptidase-4 (DPP-4) inhibition with linagliptin reduces western diet-induced myocardial TRAF3IP2 expression, inflammation and fibrosis in female mice. Cardiovasc Diabetol. 2017;16:61.CrossRefPubMedPubMedCentral
42.
go back to reference Darsalia V, Ortsater H, Olverling A, Darlöf E, Wolbert P, Nyström T, et al. The DPP-4 inhibitor linagliptin counteracts stroke in the normal and diabetic mouse brain: a comparison with glimepiride. Diabetes. 2013;62:1289–96.CrossRefPubMedPubMedCentral Darsalia V, Ortsater H, Olverling A, Darlöf E, Wolbert P, Nyström T, et al. The DPP-4 inhibitor linagliptin counteracts stroke in the normal and diabetic mouse brain: a comparison with glimepiride. Diabetes. 2013;62:1289–96.CrossRefPubMedPubMedCentral
43.
go back to reference Ma RC, Del Prato S, Gallwitz B, Shivane VK, Lewis-D’Agostino D, Bailes Z, et al. Oral glucose lowering with linagliptin and metformin compared with linagliptin alone as initial treatment in Asian patients with newly diagnosed type 2 diabetes and marked hyperglycemia: subgroup analysis of a randomized clinical trial. J Diabetes Investig. 2017. https://doi.org/10.1111/jdi.12746. Ma RC, Del Prato S, Gallwitz B, Shivane VK, Lewis-D’Agostino D, Bailes Z, et al. Oral glucose lowering with linagliptin and metformin compared with linagliptin alone as initial treatment in Asian patients with newly diagnosed type 2 diabetes and marked hyperglycemia: subgroup analysis of a randomized clinical trial. J Diabetes Investig. 2017. https://​doi.​org/​10.​1111/​jdi.​12746.
44.
go back to reference Jax T, Stirban A, Terjung A, Esmaeili H, Berk A, Thiemann S, et al. A randomised, active- and placebo-controlled, three-period crossover trial to investigate short-term effects of the dipeptidyl peptidase-4 inhibitor linagliptin on macro- and microvascular endothelial function in type 2 diabetes. Cardiovasc Diabetol. 2017;16:13.CrossRefPubMedPubMedCentral Jax T, Stirban A, Terjung A, Esmaeili H, Berk A, Thiemann S, et al. A randomised, active- and placebo-controlled, three-period crossover trial to investigate short-term effects of the dipeptidyl peptidase-4 inhibitor linagliptin on macro- and microvascular endothelial function in type 2 diabetes. Cardiovasc Diabetol. 2017;16:13.CrossRefPubMedPubMedCentral
45.
go back to reference Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke. 2001;32:2426–32.CrossRefPubMed Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke. 2001;32:2426–32.CrossRefPubMed
46.
go back to reference Darsalia V, Nathanson D, Nystrom T, Klein T, Sjoholm A, Patrone C. GLP-1R activation for the treatment of stroke: updating and future perspectives. Rev Endocr Metab Disord. 2013;62:1289–96. Darsalia V, Nathanson D, Nystrom T, Klein T, Sjoholm A, Patrone C. GLP-1R activation for the treatment of stroke: updating and future perspectives. Rev Endocr Metab Disord. 2013;62:1289–96.
47.
go back to reference Holmstedt CA, Turan TN, Chimowitz MI. Atherosclerotic intracranial arterial stenosis: risk factors, diagnosis, and treatment. Lancet Neurol. 2013;12:1106–14.CrossRefPubMedPubMedCentral Holmstedt CA, Turan TN, Chimowitz MI. Atherosclerotic intracranial arterial stenosis: risk factors, diagnosis, and treatment. Lancet Neurol. 2013;12:1106–14.CrossRefPubMedPubMedCentral
48.
go back to reference International DE, DECODA Study Group. Cardiovascular risk profile assessment in glucose-intolerant Asian individuals—an evaluation of the World Health Organization two-step strategy: the DECODA Study (Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Asia). Diabet Med. 2002;19:549–57.CrossRef International DE, DECODA Study Group. Cardiovascular risk profile assessment in glucose-intolerant Asian individuals—an evaluation of the World Health Organization two-step strategy: the DECODA Study (Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Asia). Diabet Med. 2002;19:549–57.CrossRef
49.
go back to reference DECODE Study Group, European Diabetes Epidemiology Study Group. Will new diagnostic criteria for diabetes mellitus change phenotype of patients with diabetes? Reanalysis of European epidemiological data. DECODE Study Group on behalf of the European Diabetes Epidemiology Study Group. BMJ. 1998;317:371–5.CrossRef DECODE Study Group, European Diabetes Epidemiology Study Group. Will new diagnostic criteria for diabetes mellitus change phenotype of patients with diabetes? Reanalysis of European epidemiological data. DECODE Study Group on behalf of the European Diabetes Epidemiology Study Group. BMJ. 1998;317:371–5.CrossRef
50.
go back to reference Ma RC. Acarbose: an alternative to metformin for first-line treatment in type 2 diabetes? Lancet Diabetes Endocrinol. 2014;2:6–7.CrossRefPubMed Ma RC. Acarbose: an alternative to metformin for first-line treatment in type 2 diabetes? Lancet Diabetes Endocrinol. 2014;2:6–7.CrossRefPubMed
51.
go back to reference Zhu Q, Tong Y, Wu T, Li J, Tong N. Comparison of the hypoglycemic effect of acarbose monotherapy in patients with type 2 diabetes mellitus consuming an Eastern or Western diet: a systematic meta-analysis. Clin Ther. 2013;35:880–99.CrossRefPubMed Zhu Q, Tong Y, Wu T, Li J, Tong N. Comparison of the hypoglycemic effect of acarbose monotherapy in patients with type 2 diabetes mellitus consuming an Eastern or Western diet: a systematic meta-analysis. Clin Ther. 2013;35:880–99.CrossRefPubMed
52.
go back to reference Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet. 2002;359:2072–7.CrossRefPubMed Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet. 2002;359:2072–7.CrossRefPubMed
53.
go back to reference Weng J, Soegondo S, Schnell O, Sheu WH, Grzeszczak W, Watada H, et al. Efficacy of acarbose in different geographical regions of the world: analysis of a real-life database. Diabetes Metab Res Rev. 2015;31:155–67.CrossRefPubMed Weng J, Soegondo S, Schnell O, Sheu WH, Grzeszczak W, Watada H, et al. Efficacy of acarbose in different geographical regions of the world: analysis of a real-life database. Diabetes Metab Res Rev. 2015;31:155–67.CrossRefPubMed
Metadata
Title
Linagliptin and cardiovascular outcomes in type 2 diabetes after acute coronary syndrome or acute ischemic stroke
Authors
Yan-Rong Li
Sung-Sheng Tsai
Dong-Yi Chen
Szu-Tah Chen
Jui-Hung Sun
Hung-Yu Chang
Miaw-Jene Liou
Tien-Hsing Chen
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2018
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-017-0655-y

Other articles of this Issue 1/2018

Cardiovascular Diabetology 1/2018 Go to the issue