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

Background/Purpose. To compare efficacy and safety of short- and long-acting GLP-1 receptor agonists (GLP-1 RAs), both used in combination with basal insulin in patients with type 2 diabetes.

Data Sources/Study Selection. Randomized controlled trials comparing the co-administration 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/Data Synthesis. 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.

Limitations. 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 HbA_1c (∆ - 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 HbA_1c target < 7.0% (< 53 mmol/mol; p= 0.03) more than the short-acting ones. Patients reporting symptomatic (p= 0.048), but not severe hypoglycemia (p= 0.96) were fewer with long- vs. short-acting GLP-1 RAs added to insulin. The proportion of patients reporting nausea (- 52 %; p < 0.0001) or vomiting (- 36 %; p= 0.0002) was lower 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 gastro-intestinal tolerability.