medwireNews: Adding the dipeptidyl peptidase (DPP)-4 inhibitor alogliptin to metformin and sulfonylurea treatment may improve glycemic control in patients with type 2 diabetes and high cardiovascular (CV) risk, a post-hoc analysis of the EXAMINE trial suggests.
The primary trial results demonstrated that patients with type 2 diabetes and a recent acute coronary syndrome who were randomly assigned to receive alogliptin in addition to standard care had comparable CV event rates to those allocated to placebo plus standard care, explain William White (University of Connecticut School of Medicine, Farmington, USA) and colleagues.
In the post-hoc analysis, the researchers compared glycemic control between the two groups in a subgroup of 1398 patients who were receiving dual therapy with metformin and a sulfonylurea at baseline.
As reported in The American Journal of Medicine, the 693 patients treated with alogliptin in addition to metformin and a sulfonylurea experienced a significantly greater improvement in glycated hemoglobin (HbA1c) levels over a median 18 months of follow-up compared with the 705 patients in the placebo group, with a least-squares mean decrease of 4 mmol/mol versus an increase of 2 mmol/mol, from a baseline value of 65 mmol/mol in both groups.
These findings remained consistent when the 343 patients who received additional antihyperglycemic drugs were excluded from the analysis; patients in the alogliptin group experienced a 5 mmol/mol decrease in average HbA1c levels, whereas those given placebo had a 2 mmol/mol increase.
Participants receiving alogliptin also had significantly lower rates of CV and all-cause mortality than those in the placebo group, with rates of 3.9% versus 10.5% (hazard ratio [HR]=0.49) and 5.7% versus 10.5% (HR=0.61), respectively.
“[T]hese findings of a reduction in CV death in patients on alogliptin on a background therapy of metformin and sulfonylureas support the cardiovascular safety of using the drug in a triple therapy regimen for patients with type 2 diabetes and high levels of cardiovascular risk,” write White and colleagues.
They note that alogliptin-treated patients had numerically higher rates of hypoglycemia than patients given placebo (8.8 vs 6.7%). However, the difference did not reach statistical significance, and the researchers caution that “the study design did not stipulate precise definitions of hypoglycemia,” meaning it may “have been underpowered to identify differences in hypoglycemia.”
And the researchers conclude that taken together, the efficacy and safety findings “are largely in line with those reported in randomized, controlled trials of other DPP-4 inhibitors specifically designed to evaluate their glycemic effects when used in triple therapy with metformin and a sulfonylurea.”
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