Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA) plus Basal Insulin vs. GLP-1RA in Type 2 Diabetes Mellitus—A Systematic Review and Meta-analysis

Abstract

Combination therapy with Glucagon-like peptide-1 receptor agonist (GLP-1RA) and basal insulin represents a new therapeutic option for diabetes mellitus. We hypothesized that GLP-1RA plus basal insulin is more efficacious, safer and tolerable than GLP-1RA for patients with type 2 diabetes mellitus (T2DM). Randomized controlled trials (RCTs) comparing GLP-1RA plus basal insulin vs. GLP-1RA were searched using PubMed, Cochrane library and www.ClinicalTrials.gov database. Inclusion criteria were: (1) RCTs; (2) comparison between GLP-1RA plus basal insulin vs. GLP-1RA; (3) duration of treatment between 24-30 weeks; and (4) T2DM. Four RCTs with 2,732 participants were included in this meta-analysis. Compared with GLP-1RA alone, GLP-1RA plus basal insulin was associated with a significant reduction in HbA1c (Mean difference [MD]: -0.79%; 95% CI [confidence interval]: -0.96,-0.61; P<0.001) and fasting plasma glucose (FPG) (MD: -2.03mmol/l; 95% CI: -2.28, -1.77; p<0.001). More participants achieved HbA1c ≤7% in the GLP-1RA plus basal insulin group (Odds ratio [OR]: 4.66; 95% CI: 3.00, 7.23; p<0.001). GLP-1RA plus basal insulin was associated with more symptomatic hypoglycaemia (OR: 7.04; 95% CI: 3.81, 13.00; p<0.001) and weight gain (MD: 2.46kg; 95% CI: 2.08, 2.84; P<0.001). There was no significant difference in treatment emergent adverse effects (OR: 0.80; 95% CI: 0.57, 1.11; p=0.18) and discontinuation due to adverse events (OR: 0.52; 95% CI: 0.26, 1.03; p=0.06) between both groups. GLP-1RA plus basal insulin is more efficacious for HbA1c and FPG reduction when compared with GLP-1RA in patients with T2DM. Symptomatic hypoglycaemia and weight gain were more common with GLP-1RA plus basal insulin, but discontinuation due to adverse events was similar between both groups. Disclosure M.M. Satti: None. T. O'Brien: Advisory Panel; Self; Merck Sharp & Dohme Corp., Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca. A. Liew: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S.