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

Sonal Singh, Eugene E. Wright, Anita Y M Kwan, Juliette C. Thompson, Iqra A. Syed, Ellen E. Korol, Nathalie A. Waser, Maria B. Yu, Rattan Juneja

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)228-238
Number of pages11
JournalDiabetes, Obesity and Metabolism
Volume19
Issue number2
DOIs
StatePublished - Feb 1 2017
Externally publishedYes

Fingerprint

Insulins
Type 2 Diabetes Mellitus
Meta-Analysis
Hemoglobins
Hypoglycemia
Weight Loss
Therapeutics
Randomized Controlled Trials
Hypoglycemic Agents
PubMed
MEDLINE
Pharmaceutical Preparations
Weight Gain
Glucagon-Like Peptide-1 Receptor
exenatide
Databases
Confidence Intervals
Safety
Weights and Measures
dulaglutide

Keywords

  • basal insulin
  • GLP-1 RAs
  • glycaemic control
  • meta-analysis
  • systematic review
  • type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Glucagon-like peptide-1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus : a systematic review and meta-analysis. / Singh, Sonal; Wright, Eugene E.; Kwan, Anita Y M; Thompson, Juliette C.; Syed, Iqra A.; Korol, Ellen E.; Waser, Nathalie A.; Yu, Maria B.; Juneja, Rattan.

In: Diabetes, Obesity and Metabolism, Vol. 19, No. 2, 01.02.2017, p. 228-238.

Research output: Contribution to journalArticle

Singh, Sonal ; Wright, Eugene E. ; Kwan, Anita Y M ; Thompson, Juliette C. ; Syed, Iqra A. ; Korol, Ellen E. ; Waser, Nathalie A. ; Yu, Maria B. ; Juneja, Rattan. / Glucagon-like peptide-1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus : a systematic review and meta-analysis. In: Diabetes, Obesity and Metabolism. 2017 ; Vol. 19, No. 2. pp. 228-238.
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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.",
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T2 - a systematic review and meta-analysis

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AU - Kwan, Anita Y M

AU - Thompson, Juliette C.

AU - Syed, Iqra A.

AU - Korol, Ellen E.

AU - Waser, Nathalie A.

AU - Yu, Maria B.

AU - Juneja, Rattan

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