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

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.

Cardiovascular safety of linagliptin compared with other oral glucose‐lowering agents in patients with type 2 diabetes: A sequential monitoring programme in routine care

“…Another study based on the Taiwan National Health Insurance Research Database evaluated the association between linagliptin and major CV events in a population of 1203 patients with T2D after an episode of acute coronary syndrome or ischaemic stroke. Compared with patients who did not receive any incretin‐based therapy, linagliptin users had a similar risk of major CV events (HR 1.06, 95% CI 0.66‐1.68) . These results complement our findings.…”

Atrial fibrillation and type 2 diabetes: Prevalence, etiology, pathophysiology and effect of anti‐diabetic therapies

“…In the TIMI 53 study, the DPP‐4 inhibitor saxagliptin did not reduce the incidence of NAF (0.93% vs 0.94%) . Also, in a smaller study, the outcomes of 401 participants who received linagliptin were compared with those of matched control participants who did not receive incretin‐based therapies, and the use of linagliptin was not associated with an increase in the development of NAF . Therefore, it is probable that DPP‐4 inhibitors neither increase nor decrease the incidence of NAF.…”

“…78 Also, in a smaller study, the outcomes of 401 participants who received linagliptin were compared with those of matched control participants who did not receive incretin-based therapies, and the use of linagliptin was not associated with an increase in the development of NAF. 79 Therefore, it is probable that DPP-4 inhibitors neither increase nor decrease the incidence of NAF. Based on the data described above, we can conclude that, among the drugs that lower insulin resistance, only pioglitazone and metformin, but not rosiglitazone, reduce the incidence of NAF.…”

Research update for articles published in EJCI in 2017

“…Simultaneously, another research group in Taiwan from which they identified 16 017 patients in the cohort of DPP4 inhibitor users and 74 863 patients in the cohort of DPP4 inhibitor nonusers and reported that DPP4 inhibitor therapy is associated with a decreased risk of developing NAF . However, another study identified 401 linagliptin users who had acute coronary syndrome or acute ischaemic stroke and 802 controls (matched with patient characteristics, baseline comorbidities, medication prescribed 90 days since indexed hospitalization and index year and month by propensity score) . They concluded that the risk of developing NAF was neutral between linagliptin users and nonusers.…”

“…28 However, another study identified 401 linagliptin users who had acute coronary syndrome or acute ischaemic stroke and 802 controls (matched with patient characteristics, baseline comorbidities, medication prescribed 90 days since indexed hospitalization and index year and month by propensity score). 29 They concluded that the risk of developing NAF was neutral between linagliptin users and nonusers. Thus, it is possible that DPP4 inhibitors have not been shown to increase the risk of developing NAF.…”