Incretin-based drugs unrelated to all-cause mortality in type 2 diabetes
Incretin-based treatments are not associated with higher all-cause mortality in patients with type 2 diabetes, a new meta-analysis reports.
Randomized controlled trials (RCTs) that compared dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists to placebo or other controls were searched from the databases of the Cochrane Central Register of Controlled trials, Embase and Medline.
Among the information extracted were sample characteristics, treatment details, study duration, disease parameters and mortality outcomes. The Cochrane risk of bias tool was used to evaluate methodological quality and risk of bias of the selected studies.
A total of 189 RCTs (n=155,145) were eligible for inclusion in the meta-analysis. The participants in 126 of these studies were at a low risk of cardiovascular disease; 55 studies had participants with unclear risk of cardiovascular disease, while the remaining eight had high-risk patients.
Six of the 189 RCTs were large outcome trials and had very low to no risk of reporting bias; 83.3 percent (n=5) of these had some missing outcome data. Of the remaining trials, 96.7 percent (n=177) had adequate randomization, 92.9 percent (n=170) had adequate concealment and 84.7 percent (n=155) had adequate blinding.
At least one death was reported in 112 of the 189 included trials. Meta-analysis of these studies showed no significant difference in mortality rates between controls and individuals who received incretin-based drugs (odds ratio [OR], 0.96; 95 percent CI, 0.90 to 1.02).
Univariable meta-regression by subgroup showed that length of follow-up (p=0.38), baseline cardiovascular risk (p=0.20), type of incretin medication (p=0.52), mode of treatment (p=0.80) and individual incretin agents (p=0.86) were all unrelated to all-cause mortality.
After adjusting for all potential confounders, multiple meta-regression showed that only GLP-1 agonists were associated with better all-cause mortality (p=0.01).