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

Abstract

Aims: Since 2005, several glucagon-like peptide-1 receptor agonists (GLP-1 RAs) 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 (HbA1c) 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.

Keywords: GLP-1 RAs; basal insulin; glycaemic control; meta-analysis; systematic review; type 2 diabetes.

© 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1

Study PRISMA diagram. Abbreviations: RCT, randomized clinical trial.

Figure 2

Effect of GLP‐1 RA compared to basal insulin at week 26 (±10 weeks). Change in HbA1c (%) (A), and change in bodyweight (kg) (B). Abbreviations: CI, confidence interval; GLP‐1 RA, glucagon‐like peptide‐1 receptor agonist; MD, mean difference; SD, standard deviation. *Twice daily; **once weekly.

Figure 3

Effect of GLP‐1 RA compared to basal insulin at 26 weeks (±10 weeks) on hypoglycemia, odds ratio (A), and proportion (%) (B). Abbreviations: CI, confidence interval; GLP‐1 RA, glucagon‐like peptide‐1 receptor agonist; OR, odds ratio; prop, proportion. *Twice daily; **once weekly. †At baseline, the majority of patients in each treatment group (exenatide 84.7%; insulin glargine 86.2%) were taking SUs. ††At baseline, 70.0% and 30.0% of patients in both arms were receiving MET and MET + SU, respectively. One in four patients had a reduction in SU dose. ‡SU dosage was reduced or discontinued at the physician's discretion. SUs were initially taken by 60.0% of those receiving insulin glargine and by 63.0% receiving liraglutide. At 24 weeks, 49.0% and 48.0%, respectively, were still taking them. ‡‡At baseline, 94.0% in the liraglutide arm and 95.0% in the insulin glargine arm were receiving SU. ‡‡‡The majority of the patients in the dulaglutide group (65.0%) and insulin glargine group (63.0%) received SU at baseline. In the dulaglutide and insulin glargine groups, 13/117 (11.1%) and 11/114 (9.6%) patients, respectively, decreased their concomitant SU dose from baseline as a result of hypoglycemia. §Figure includes only insulin glargine trials to highlight the differences in proportions of patients experiencing hypoglycemic events between trials, which may be due to variations in insulin titration and background therapies.