Glucagon‐like peptide‐1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus: a systematic review and meta‐analysis

Oct 8, 2016Diabetes, obesity & metabolism

Glucagon-like peptide-1 receptor drugs versus long-acting insulin for treating type 2 diabetes: a review and combined analysis

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Abstract

Once-weekly GLP-1 receptor agonists, exenatide long acting release and dulaglutide, showed greater mean reductions compared to basal insulins.

Exenatide LAR reduced HbA1c by -0.31% and dulaglutide by -0.39%, both statistically significant.
Once-daily liraglutide and twice-daily exenatide did not show significant HbA1c changes.
All GLP-1 receptor agonists resulted in mean weight reduction, while basal insulins led to mean weight gain.
Analysis of hypoglycaemia was challenged by inconsistent definitions and reporting, limiting interpretability.
The findings are based on data from 15 randomized clinical trials, with 11 included in the meta-analysis.

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AIMS: Since 2005, several glucagon-like peptide-1 receptor agonists () have been approved to treat people with type 2 diabetes. These agents are considered for use at the same point in the treatment paradigm as basal insulins. A comprehensive comparison of these drug classes, therefore, can help inform treatment decisions. This systematic review and meta-analysis assessed the clinical efficacy and safety of GLP-1 RAs compared with basal insulins.

MATERIALS AND METHODS: MEDLINE, EMBASE, CENTRAL and PubMed databases were searched. Randomized clinical trials (RCTs) of ≥16 weeks' duration comparing GLP-1 RAs vs basal insulins in adults with type 2 diabetes inadequately controlled with oral antihyperglycemic drugs were included. Data on the change from baseline to 26 weeks (±10 weeks) of treatment in hemoglobin A1c () and weight, as well as the proportion of patients experiencing hypoglycaemia, were extracted. Fixed-effect pairwise meta-analyses were conducted where data were available from ≥2 studies.

RESULTS: Fifteen RCTs were identified and 11 were meta-analysed. The once-weekly GLP-1 RAs, exenatide long acting release (LAR) and dulaglutide, led to greater, statistically significant mean HbA1c reductions vs basal insulins (exenatide: -0.31% [95% confidence interval -0.42, -0.19], dulaglutide: -0.39% [-0.49, -0.29]) whilst once-daily liraglutide and twice-daily exenatide did not (liraglutide: 0.06% [-0.06, 0.18], exenatide: 0.01% [-0.11, 0.13]). Mean weight reduction was seen with all GLP-1 RAs while mean weight gain was seen with basal insulins. Interpretation of the analysis of hypoglycaemia was limited by inconsistent definitions and reporting. Because of the limited number of available studies sensitivity analyses to explore heterogeneity could not be conducted.

CONCLUSIONS: Although weight reduction is seen with all GLP-1 RA's, only the once-weekly agents, exenatide LAR and dulaglutide, demonstrate significant HbA1c reductions when compared to basal insulins.

Key numbers

-0.31%

Reduction with Exenatide LAR

Mean change in at 26 weeks vs. basal insulin

-4.65 kg

Weight Loss with Liraglutide

Mean weight change at 26 weeks vs. basal insulin

0.32

Odds Ratio for Hypoglycemia with Exenatide LAR

Odds ratio for hypoglycemic episodes vs. insulin glargine

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Glucagon‐like peptide‐1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus: a systematic review and meta‐analysis

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