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

Conrad Eng; Caroline K Kramer; Bernard Zinman; Ravi Retnakaran

doi:10.1016/S0140-6736(14)61335-0

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

Lancet. 2014 Dec 20;384(9961):2228-34. doi: 10.1016/S0140-6736(14)61335-0. Epub 2014 Sep 11.

Authors

Conrad Eng¹, Caroline K Kramer², Bernard Zinman³, Ravi Retnakaran⁴

Affiliations

¹ Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON, Canada.
² Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON, Canada; Division of Endocrinology, University of Toronto, Toronto, ON, Canada.
³ Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Division of Endocrinology, University of Toronto, Toronto, ON, Canada.
⁴ Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON, Canada; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Division of Endocrinology, University of Toronto, Toronto, ON, Canada. Electronic address: rretnakaran@mtsinai.on.ca.

PMID: 25220191
DOI: 10.1016/S0140-6736(14)61335-0

Abstract

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.

Publication types

Meta-Analysis
Review
Systematic Review

MeSH terms

Diabetes Mellitus, Type 2 / drug therapy*
Drug Therapy, Combination
Glycated Hemoglobin / analysis
Humans
Hypoglycemic Agents / therapeutic use*
Insulin, Long-Acting / therapeutic use*
Randomized Controlled Trials as Topic
Receptors, Glucagon / agonists*
Weight Loss

Substances

Glycated Hemoglobin A
Hypoglycemic Agents
Insulin, Long-Acting
Receptors, Glucagon
hemoglobin A1c protein, human