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

• Published in: The Lancet (British edition) 2014-12, Vol.384 (9961), p.2228-2234
• Main Authors: Eng, Conrad, MSc, Kramer, Caroline K, MD, Zinman, Bernard, Prof, Retnakaran, Ravi, Dr
• Format: Article
• Language: English
• Subjects: Clinical trials; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Drug therapy; Drug Therapy, Combination; Glucose; Glycated Hemoglobin A - analysis; Humans; Hypoglycemia; Hypoglycemic Agents - therapeutic use; Insulin; Insulin, Long-Acting - therapeutic use; Internal Medicine; Peptides; Randomized Controlled Trials as Topic; Receptors, Glucagon - agonists; Studies; Systematic review; Weight Loss
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(14)61335-0

Summary 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 (HbA1c ) of −0·44% (95% CI −0·60 to −0·29), an improved likelihood of achieving the target HbA1c 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 HbA1c 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. Funding None.