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.

Abstract

To compare the efficacy and safety of short- and long-acting glucagon-like peptide 1 receptor agonists (GLP-1 RAs), both used in combination with basal insulin, in patients with type 2 diabetes. Randomized controlled trials comparing the coadministration of short- or long-acting GLP-1 RAs and basal insulin with basal insulin ± placebo were identified (PubMed search). Of 974 identified publications, 14 clinical trials were included. Eight trials examined short-acting and six long-acting GLP-1 RAs. Differences in HbA_1c, fasting plasma glucose, body weight, and adverse events were compared between studies using short- or long-acting GLP-1 RAs by random-effects meta-analysis. There were relatively small numbers of available publications, some heterogeneity regarding protocols, and differences in the GLP-1 RA compound used. Long-acting GLP-1 RAs more effectively reduced HbA_1c (∆ -6 mmol/mol [95% CI -10; -2], <i>P</i> = 0.007), fasting plasma glucose (∆ -0.7 mmol/L [-1.2; -0.3], <i>P</i> = 0.007), and body weight (∆ -1.4 kg [-2.2; -0.6], <i>P</i> = 0.002) and raised the proportion of patients achieving an HbA_1c target <7.0% (<53 mmol/mol) (<i>P</i> = 0.03) more than the short-acting ones. Patients reporting symptomatic (<i>P</i> = 0.048) but not severe (<i>P</i> = 0.96) hypoglycemia were fewer with long- versus short-acting GLP-1 RAs added to insulin. A lower proportion of patients reported nausea (-52%, <i>P</i> < 0.0001) or vomiting (-36%, <i>P</i> = 0.0002) with long-acting GLP-1 RAs. Overall, GLP-1 RAs improved HbA_1c, fasting plasma glucose, and body weight when added to basal insulin. However, long-acting GLP-1 RAs were significantly more effective for glycemic and body weight control and displayed better gastrointestinal tolerability.