Review compares once-weekly GLP-1 receptor agonists to other diabetes meds

Once-weekly glucagon-like peptide 1 (GLP-1) receptor agonists lower HbA1c without increasing body weight, a review found.

The systematic review and meta-analysis looked at 33 randomized controlled trials comparing the safety and efficacy of GLP-1 receptor agonists licensed for once-weekly dosing (albiglutide, dulaglutide, or exenatide extended release) with placebo or other antidiabetic agents in adults with type 2 diabetes. Results were published online on Sept. 23 by Diabetes, Obesity and Metabolism.

The analyzed trials had a total of 16,003 participants and a duration of intervention of at least 12 weeks. Participants' mean age ranged from 52 to 63 years, and baseline mean HbA1c levels ranged from 7.1% to 8.7%. Researchers compared once-weekly GLP-1 receptor agonists against placebo (15 studies), oral antidiabetic agents (7 studies), daily GLP-1 drugs (9 studies), basal insulin (7 studies), and mealtime insulin (1 study). They performed all analyses at the 0.05 significance level.

Compared with placebo, change in HbA1c was −0.66% (6 studies; 95% CI, −1.14% to −0.19%) with albiglutide and −1.18% (7 studies; 95% CI, −1.34% to −1.02%) with dulaglutide. In lowering HbA1c percentage, once-weekly GLP-1 receptor agonists were similar to pioglitazone (3 studies) and liraglutide (4 studies) but more effective than sitagliptin (5 studies), twice-daily exenatide (5 studies), and insulin glargine (6 studies).

The researchers detected no statistically significant weight change with albiglutide or dulaglutide when compared with placebo; however, the drugs had a favorable effect on body weight compared with pioglitazone, sitagliptin, and insulin glargine. They were associated with similar body weight reductions as twice-daily exenatide but were inferior to liraglutide. Evidence is inconclusive regarding their efficacy and safety compared with mealtime insulin and daily GLP-1 receptor agonists, including liraglutide, the authors said.

Compared to placebo, the risk of hypoglycemia was similar with albiglutide but greater with dulaglutide. However, all 3 medications were associated with a higher incidence of gastrointestinal adverse events compared with placebo or sitagliptin but not versus daily GLP-1 drugs. The researchers observed an increased risk of injection-site reactions compared with other injectable antidiabetic agents. They did not find an association of the drugs with pancreatitis, cardiovascular events, or pancreatic or thyroid cancer.

The study authors concluded that once-weekly GLP-1 receptor agonists were at least as effective as oral antidiabetic agents at lowering HbA1c without increasing body weight. “Hence, given the convenience of the weekly dosing scheme, they could pose an efficient therapeutic option for patients where weight loss is not the main therapeutic priority,” they wrote.

They noted several limitations to their study, such as how the majority of trials used last-observation-carried-forward procedures to impute missing data, which can lead to bias, and how all studies received funding from pharmaceutical companies. Data were also insufficient to conduct separate analyses for clinically relevant patient subgroups.