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

Eng C
Kramer CK
Zinman B
Retnakaran R

Lancet. 2014 Dec 20;384(9961):2228-34. doi: 10.1016/S0140-6736(14)61335-0. Epub 2014 Sep 11. (Review)
PMID: 25220191

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Disciplines

Family Medicine (FM)/General Practice (GP)

Relevance - 7/7
Newsworthiness - 6/7
General Internal Medicine-Primary Care(US)

Relevance - 7/7
Newsworthiness - 6/7
Endocrine

Relevance - 6/7
Newsworthiness - 6/7
Internal Medicine

Relevance - 6/7
Newsworthiness - 5/7

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.

Clinical Comments

Endocrine

This is an excellent synthesis of the evidence in support of GLP1+insulin therapy. Critically interpreted, it supports good practice in the management of patients with type 2 diabetes. It should be tempered a little by our lack of knowledge of the potential for adverse effects and risks of the GLP1 analogues.

General Internal Medicine-Primary Care(US)

Heterogeneous comparisons, evidence of publication bias, and small differences in effect decrease confidence in the study findings. The conclusions appear overstated.

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