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

Current guidelines recommend that antihyperglycaemic 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 (BP/BB) insulin regimen. We conducted a systematic review and meta-analysis to compare the effects of GLP-1RA/insulin combinations versus BP/BB.The review was registered on PROSPERO (CRD42017079547). PubMed, Scopus, CENTRAL, and ClinicalTrials.gov were searched until July 2018. All randomized controlled trials (RCTs) reporting HbA1c , body weight, daily insulin dose, hypoglycaemic events, and discontinuation due to lack of efficacy were included. A subgroup analysis on different combinations of GLP-1RA and insulin was performed.Out of 1885 retrieved papers, 13 RCTs were included in the review. Compared with BP/BB, GLP-1RA/insulin combinations were associated with a similar HbA1c reduction (Δ = -0.06%; 95% confidence interval [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 hypoglycaemic events (relative risk [RR] = 0.46; 95% CI, 0.38-0.55; P < 0.001; I2 = 99%). The daily insulin dosage 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.The present review supports treatment intensification with GLP-1RA added to insulin versus BP/BB in uncontrolled type 2 diabetes. This could provide similar antihyperglycaemic efficacy while leading to weight loss and sparing of hypoglycaemia 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.