Long-Acting GLP-1 RAs More Effective than Short-Acting for Diabetes Management

New research from an analysis of more than a dozen clinical trials suggests long-acting glucagon-like peptide 1 receptor agonists (GLP-1 RA) were more effective for managing diabetes than short-acting GLP-1 RAs among patients type 2 diabetes on background basal insulin.

Results of the analysis indicate long-acting GLP-1 RAs were not only more effective at reducing HbA1c, fasting plasma glucose, and body weight compared to short-acting GLP-1 RAs, but the long-acting agents also had an improved safety profile with lower rates of nausea and vomiting among patients.

“This is novel information not available from previous meta-analyses and provides meaningful guidance for the choice of GLP-1 RAs to be used in combination with basal insulin,” wrote study investigators. “The results regarding HbA1c and fasting plasma glucose reduction resemble previous findings in clinical trials comparing short- with long-acting GLP-1 RAs on a background of oral glucose-lowering medications.”

To further compare the safety and efficacy of short- and long-acting GLP-1 RAs in combination with basal insulin, a trio of investigators from the St. Josef-Hospital in Bochum, Germany designed a meta-analysis with the aim of using data from randomized clinical trials to describe associations between the agents and management of diabetes as well as adverse events. Through a search of the PubMed database from inception through December 2018, investigators identified 974 potential articles for inclusion in their study. Of these 974, 14 met the investigators' criteria for inclusion.

Of the 14 trials included in the analysis, 8 reported on a combination with short-acting GLP-1 RAs and 6 reported oolong-acting GLP-1 RAs. Studies included were required to report baseline and end of study measurements related to HbA1c, fasting plasma glucose, body weight, adverse events, prevalence of hypoglycemia, and proportion of patients prematurely discontinuing treatment. The minimum duration for inclusion in the analysis was 6 weeks.

Results of the investigators analysis suggested long-acting GLP-1 RAs more effectively reduced HbA1c (-6 mmol/mol; 95% CI, -10 to -2; P=.007), fasting plasma glucose (-0.7 mmol/mol; 95% CI, -1.3 to-0.3; P=.007), and body weight (-1.4 kg; -2.2 to -0.6; P=.002) when compared against short-acting GLP-1 RAs. Results also indicated long-acting GLP-1 RA use resulted in a greater proportion of patients achieving a target HbA1c of less than 7% (27.3% vs 24.4%, P=.048).

In regard to safety, investigators found fewer patients reported symptomatic hypoglycemia with long-acting GLP-1 RAs versus short-acting GLP-1 RAs (P=.048) but noted the proportion of patients reporting severe episodes of hypoglycemia was low and not significantly different between groups (P=.96). Additionally, a lower proportion of patients receiving long-acting GLP-1 RAs reported experiencing nausea (-52%, P <.0001) or vomiting (-36%, P=.0002).

Investigators noted results of the meta-analysis indicated both short- and long-acting GLP-1 RAs improved HbA1c, fasting plasma glucose, and body weight when added to basal insulin regimens.

“The results of our meta-analysis indicate that long-acting GLP-1 RAs should preferentially be combined with basal insulin, since this combination results in not only better overall glycemic control (HbA1c) but also improved fasting plasma glucose concentrations and lower body weight. This combination also has advantages regarding gastrointestinal adverse events,” investigators wrote.

This study, “Efficacy and Safety of Short- and Long-Acting Glucagon-Like Peptide 1 Receptor Agonists on a Background of Basal Insulin in Type 2 Diabetes: A Meta-analysis,” was published in Diabetes Care.