GLP-1 Receptor Agonist Added to Insulin versus Basal-plus or Basal-bolus Insulin Therapy in Type 2 Diabetes: A Systematic Review and Meta-analysis

Aims Current guidelines recommend that anti‐hyperglycemic treatment in patients with type 2 diabetes not achieving the HbA1c target on basal insulin should be intensified with a glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) or basal‐plus/basal‐bolus insulin regimen (BP/BB). We conducted a systematic review and meta‐analysis to compare the effects of GLP‐1RA/insulin combinations versus BP/BB. Materials and methods The review was registered on PROSPERO (CRD42017079547). PubMed, Scopus, CENTRAL and Clinicaltrials.gov were searched until July 2018. All RCTs reporting HbA1c, body weight, daily insulin dose, hypoglycemic events and discontinuation due to lack of efficacy were included. A subgroup analysis on different combinations of GLP‐1RA and insulin was performed. Results Out of 1,885 retrieved papers, 13 RCTs were included in the review. Compared to BP/BB, GLP‐1RA/insulin combinations were associated with a similar HbA1c reduction (Δ=‐0.06%; 95%CI ‐0.14 to 0.02; p=0.13; I²=52%), greater weight loss (Δ=‐3.72 kg; 95%CI ‐4.49 to ‐2.95; p<0.001; I²=89%) and lower incidence of hypoglycemic events (RR=0.46; 95%CI 0.38 to 0.55; p<0.001; I²=99%). The daily insulin dose among GLP‐1RA/insulin users was 30.3 IU/day (95%CI ‐41.2 to ‐19.3; p<0.001; I²=94%), lower than with BP/BB. No difference was found for discontinuation due to lack of efficacy. Conclusions The present review supports treatment intensification with GLP‐1RA added to insulin versus BP/BB in uncontrolled type 2 diabetes. This could provide similar anti‐hyperglycemic efficacy while leading to weight loss and sparing of hypoglycemia and insulin dose. As a consequence, a considerable number of patients with type 2 diabetes could be potentially shifted from BP/BB to GLP‐1RA/insulin combinations.