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‘Reassuring’ safety data in two antihyperglycaemics

ESC Congress News 2015 - London

Patients with type-2 diabetes (T2DM) can safely take two antihyperglycemic drugs without increasing the risk of CVD complications, including heart failure, according to two separate studies presented at a Hot Line session yesterday.

Diabetes and the Heart
Cardiovascular Pharmacotherapy

ELIXA investigator Eldrin Lewis described lixisenatide as a ‘safe way’ to reduce glucose. Paul Armstrong described risk findings from the TECOS study of sitagliptin as ‘reassuring’.Both the Evaluation of LIXisenatide in Acute Coronary Syndrome (ELIXA) and the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) found there was no increased risk, even if patients had a history of heart failure.

Prior studies have established an association between anti-diabetic therapy and increased incidence of HF.

Indeed, observations from SAVOR-TIMI 53 and also EXAMINE, two recent large trials, suggest an increased risk for hospitalisation for HF with the DPP-4 inhibitors saxagliptin and alogliptin respectively. This has prompted the European Medicines Agency and FDA to establish guidelines for clinical trials to ensure cardiovascular safety in glucose-lowering therapies. Thus, both the TECOS and ELIXA studies had important safety components in their design.

The core data from these two trials were presented at the American Diabetes Association congress in June. ELIXA was powered to establish non-inferiority and superiority of lixisenatide, a glucagon-like peptide-1 receptor agonist, over a minimum of 10 months. The study followed 6068 patients with T2DM and a history of MI (83%) or hospitalisation for unstable angina within the past six months following randomisation to daily injections of lixisenatide (n = 3034) or placebo (n = 3034). The primary endpoint was CV death, MI, stroke or unstable angina with a key secondary endpoint of HF hospitalisation.

The study found that the primary outcome occurred in 13.4% of the lixisenatide group and in 13.2% of the placebo group (HR 1.02; 95% CI 0.89-1.17), prompting study presenter Eldrin Lewis, from Harvard Medical School Brigham and Women’s Hospital, US, to conclude that lixisenatide was ‘a safe way of reducing glucose’. He reminded his audience that lixisenatide’s efficacy in lowering blood glucose had already been clearly demonstrated in earlier ‘metabolic’ studies.

The TECOS trial, said presenter Paul Armstrong from the University of Alberta, Canada, randomised 14,671 patients with T2DM and established CVD to the dipeptidyl peptidase-4 inhibitor sitagliptin (n = 7332) or placebo (n =7 339) in addition in both groups to usual care to achieve glycaemic control.

The primary aim of the study, he explained, was to demonstrate non-inferior cardiovascular risk between patients treated with sitagliptin plus usual care and with usual care alone plus placebo. The prespecified secondary endpoint was to analyse effects on hospitalisation for heart failure and related outcomes.

Results showed that sitagliptin did indeed meet the primary endpoint of non-inferiority to placebo (HR 0.98; 95% CI 0.88-1.09; P=<0.001) after a median follow-up of two years. Hospitalisation for HF was 3.1% for both groups (HR 1.00; 95% CI 0.84-1.20; P=0.95), and hospitalisation for HF or cardiovascular death was 7.3% for the sitagliptin group and 7.2% for the placebo (HR 1.2; 95% CI; P=0.81).

Armstrong described the findings as ‘reassuring’ to patients and prescribers. He said: ‘We can clearly conclude that sitagliptin can be safely used in T2DM patients without concern for worsening heart failure.’