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

Background Current guidelines recommend that antihyperglycaemic treatment in patients with type 2 diabetes not achieving the HbA(1c) 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. Methods The review was registered on PROSPERO (CRD42017079547). PubMed, Scopus, CENTRAL, and were searched until July 2018. All randomized controlled trials (RCTs) reporting HbA(1c), 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. Results 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 HbA(1c) reduction (Delta = -0.06%; 95% confidence interval [CI], -0.14 to 0.02; P = 0.13; I-2 = 52%), greater weight loss (Delta = -3.72 kg; 95% CI, -4.49 to -2.95; P I-2 = 89%), and lower incidence of hypoglycaemic events (relative risk [RR] = 0.46; 95% CI, 0.38-0.55; P I-2 = 99%). The daily insulin dosage among GLP-1RA/insulin users was 30.3 IU/day (95% CI, -41.2 to -19.3; P I-2 = 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 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.