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

PURPOSE 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. DATA SOURCES AND STUDY SELECTION 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. DATA EXTRACTION AND DATA SYNTHESIS Differences in HbA1c, 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. LIMITATIONS There were relatively small numbers of available publications, some heterogeneity regarding protocols, and differences in the GLP-1 RA compound used. CONCLUSIONS Long-acting GLP-1 RAs more effectively reduced HbA1c (∆ −6 mmol/mol [95% CI −10; −2], P = 0.007), fasting plasma glucose (∆ −0.7 mmol/L [−1.2; −0.3], P = 0.007), and body weight (∆ −1.4 kg [−2.2; −0.6], P = 0.002) and raised the proportion of patients achieving an HbA1c target <7.0% (<53 mmol/mol) (P = 0.03) more than the short-acting ones. Patients reporting symptomatic (P = 0.048) but not severe (P = 0.96) hypoglycemia were fewer with long- versus short-acting GLP-1 RAs added to insulin. A lower proportion of patients reported nausea (−52%, P < 0.0001) or vomiting (−36%, P = 0.0002) with long-acting GLP-1 RAs. Overall, GLP-1 RAs improved HbA1c, 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.