Lixisenatide treatment improves glycaemic control in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin with or without sulfonylurea: a randomized, double-blind, placebo-controlled, 24-week trial (GetGoal-M-Asia).

BACKGROUND: This study assessed the efficacy and safety of the once-daily glucagon-like peptide-1 receptor agonist, lixisenatide, in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin ± sulfonylurea. METHODS: In this 24-week, double-blind, placebo-controlled, multinational study, patients were randomized to lixisenatide 20 µg once daily or placebo. The primary endpoint was absolute change in glycated haemoglobin (HbA1c ) from baseline to week 24. RESULTS: A total of 391 patients were randomized. Lixisenatide significantly reduced HbA1c levels compared with placebo (LS mean difference: -0.36%, p = 0.0004). A significantly higher proportion of lixisenatide-treated patients achieved HbA1c targets of <7% (p = 0.003) and ≤6.5% (p = 0.001) versus placebo. Lixisenatide was associated with a statistically significant reduction in 2-h postprandial plasma glucose after a standardized breakfast versus placebo (LS mean difference: -4.28 mmol/L, p < 0.0001) and a significant reduction in fasting plasma glucose (p = 0.0109). There was no difference in weight loss versus placebo, with a modest reduction in body weight reported for both groups (lixisenatide: -1.50 kg, placebo: -1.24 kg; p = 0.296). The incidence of treatment-emergent adverse events (TEAEs) was 64.3% with lixisenatide versus 47.4% with placebo, with serious TEAEs reported in 1.5% versus 2.1% of patients, respectively. The most common TEAE in the lixisenatide group was nausea (16.3% vs 2.6% with placebo). The incidence of symptomatic hypoglycaemia was 5.6% with lixisenatide treatment and 2.6% with placebo (p = 0.1321), with no severe symptomatic hypoglycaemia events reported. CONCLUSIONS: In Asian patients with type 2 diabetes mellitus insufficiently controlled on metformin ± sulfonylurea, lixisenatide significantly improved glycaemic control and was well tolerated during the 24-week study.

The importance of glycated haemoglobin (HbA(1c)) and postprandial glucose (PPG) control on cardiovascular outcomes in patients with type 2 diabetes.

Vascular complications are the leading cause of morbidity and mortality in type 2 diabetes. Cardiovascular disease is significantly more common in patients with type 2 diabetes than in non-diabetics, and accounts for more than two-thirds of deaths associated with the condition. Many physicians believe that hyperglycaemia is responsible, at least in part, for this additional risk. The benefit of improved glycaemic control on microvascular complications is well established and recent trials have attempted to clarify the role of glycaemic control on macrovascular outcomes. This article reviews the recent evidence from a post-interventional analysis of the UKPDS and the ACCORD, ADVANCE, VADT and HEART2D trials for an association between elevated blood glucose levels and vascular complications. The data suggest that improved glycaemic control has the potential to significantly reduce the risk of micro- and macrovascular disease when instigated early in the disease course. However, in more advanced diabetes, the benefits of improved control appear to be less evident. Recent studies have also suggested that controlling postprandial glucose may be an important component in the reduction of vascular complications. Taken together, these studies indicate that glycaemic control remains a key cornerstone in the management of type 2 diabetes.