Clinician Article
Glucagon-like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes: a systematic review and meta-analysis.
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Family Medicine (FM)/General Practice (GP)Relevance - 7/7
Newsworthiness - 6/7 -
General Internal Medicine-Primary Care(US)Relevance - 7/7
Newsworthiness - 6/7 -
EndocrineRelevance - 6/7
Newsworthiness - 6/7 -
Internal MedicineRelevance - 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路44% (95% CI -0路60 to -0路29), an improved likelihood of achieving the target HbA1c of 7路0% or lower (relative risk [RR] 1路92; 95% CI 1路43 to 2路56), no increased relative risk of hypoglycaemia (0路99; 0路76 to 1路29), and a mean reduction in weight of -3路22 kg (-4路90 to -1路54). Furthermore, compared with basal-bolus insulin regimens, the combination treatment yielded a mean reduction in HbA1c of -0路1% (-0路17 to -0路02), with lower relative risk of hypoglycaemia (0路67, 0路56 to 0路80), and reduction in mean weight (-5路66 kg; -9路8 to -1路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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