Glucagon-like peptide-1 receptor agonist and basal insulin combination tre atment for the management of type 2 diabetes: a systematic review and meta-analysis

Background Combination treatment with a glucagon-like peptide-1 (GLP-1) agonist and basal insulin has been proposed as a treatment strategy for type 2 diabetes that could provide robust glucose-lowering capability with low risk of hypoglycaemia or weight gain. We thus did a systematic review and meta-analysis of randomised controlled trials to assess the effect of this combination treatment on glycaemic control, hypoglycaemia, and weight gain in patients with type 2 diabetes. Methods We systematically searched PubMed, Embase, Cochrane, Web of Knowledge, FDA.gov, and ClinicalTrials.gov for randomised controlled trials (published between Jan 1, 1950, and July 29, 2014; no language restrictions) comparing GLP-1 agonist and basal insulin combination treatment to other anti-diabetic treatments. Our main endpoints were glycaemic control, hypoglycaemia, and change in weight. We assessed pooled data by use of a random-effects model. Findings Of 2905 identified studies, 15 were eligible and were included in our analysis (N=4348 participants). Compared with other anti-diabetic treatments, GLP-1 agonist and basal insulin combination treatment yielded an improved mean reduction in glycated haemoglobin (HbA(1c)) of -0.44% (95% CI -0.60 to -0.29), an improved likelihood of achieving the target HbA(1c) of 7.0% or lower (relative risk [RR] 1.92; 95% CI 1.43 to 2.56), no increased relative risk of hypoglycaemia (0.99; 0.76 to 1.29), and a mean reduction in weight of -3.22 kg (-4.90 to -1.54). Furthermore, compared with basal-bolus insulin regimens, the combination treatment yielded a mean reduction in HbA(1c) of -0.1% (-0.17 to -0.02), with lower relative risk of hypoglycaemia (0.67, 0.56 to 0.80), and reduction in mean weight (-5.66 kg; -9.8 to -1.51). Interpretation GLP-1 agonist and basal insulin combination treatment can enable achievement of the ideal trifecta in diabetic treatment: robust glycaemic control with no increased hypoglycaemia or weight gain. This combination is thus a potential therapeutic strategy that could improve the management of patients with type 2 diabetes.