Clinician Article

Efficacy and safety of once-weekly glucagon-like peptide-1 receptor agonists compared with exenatide and liraglutide in type 2 diabetes: a systemic review of randomised controlled trials.

  • Xue X
  • Ren Z
  • Zhang A
  • Yang Q
  • Zhang W
  • Liu F
Int J Clin Pract. 2016 Aug;70(8):649-56. doi: 10.1111/ijcp.12847. Epub 2016 Jul 25. (Review)
PMID: 27456750
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  • Family Medicine (FM)/General Practice (GP)
    Relevance - 5/7
    Newsworthiness - 5/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 5/7
    Newsworthiness - 5/7
  • Internal Medicine
    Relevance - 5/7
    Newsworthiness - 5/7
  • Endocrine
    Relevance - 5/7
    Newsworthiness - 4/7


BACKGROUND: Once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promising results in the treatment of type 2 diabetes. Herein, we compared the efficacy and safety of once-weekly GLP-1RAs with exenatide and liraglutide separately.

METHODS: We systematically surveyed the pertinent literature using various databases. The randomised controlled trials that compared once-weekly GLP-1RAs with exenatide and liraglutide in type 2 diabetes were included. Our main end-points were control of glycaemia, body weight, hypoglycaemia and gastrointestinal adverse events (AEs).

RESULTS: Our analysis included eight trials involving 5531 patients. Exenatide-long-acting release (LAR), dulaglutide and taspoglutide were more effective than twice-daily exenatide in reducing glycosylated haemoglobin A1c (HbA1c) and fasting blood glucose (FBG) levels and achieving HbA1c targets (< 7.0% and = 6.5%). Liraglutide was as effective as dulaglutide and more effective than exenatide-LAR and albiglutide in controlling glycaemia. With regard to the effectiveness in decreasing body weight, exenatide-LAR, dulaglutide and taspoglutide were similar to exenatide whereas exenatide-LAR, dulaglutide and albiglutide were inferior to liraglutide. Once-weekly GLP-1RAs, exenatide and liraglutide resulted in a similar incidence of hypoglycaemia and of gastrointestinal, serious, or other AEs.

CONCLUSIONS: Once-weekly GLP-1RAs were more effective in controlling glycaemia and equally effective in decreasing body weight than twice-daily exenatide but were inferior to liraglutide in controlling these two parameters (dulaglutide was similar with liraglutide in controlling glycaemia). Once-weekly GLP-1RAs, exenatide and liraglutide had a similar risk of causing AEs.

Clinical Comments


This is confirmation that the long-acting GLP-1 agonists are as effective in lowering glucose as the short-acting, and they do not appear to have more side effects. As these drugs have to be given by s/c injection, once weekly is obviously more attractive than once or twice daily, and may improve adherence. Maybe the short-acting versions are already becoming redundant.


It is very difficult for a physician to go for injectable forms of anti-hyperglycemic agents; insulin, GLP-1RAs and even pramilintide when traditional oral agents are not adequate to achieve glycemic target. Incretins, specifically GLP-1RAs are the novel agents, which reduces hyperglycemia through glucose dependent manner. Once weekly GLP-RAs means one shot per week instead of 7 or 14 shots. Once weekly will obviously increase treatment adherence as well as better prognosis.

Family Medicine (FM)/General Practice (GP)

It's relevant and newsworthy that weekly GLP-1 agonists drop Hba1c more than B.I.D exenatide, but not as much as liraglutide, in mostly open label, drug company sponsored studies. Real outcome data, rather than making numbers look nicer, would be better, but it's harder to study. These drugs are unaffordable for most of my patients.

General Internal Medicine-Primary Care(US)

Liraglutide is the big winner based on this M-A.

Internal Medicine

As a general internist practicing in the U.S., I find that insurance coverage, or lack of it, is a major determinant in the diabetes medications available to my patients.

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