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Battle of the GLP-1 Agonists: Liraglutide vs. Exenatide

Liraglutide may help type 2 diabetes patients achieve tighter glycemic control with fewer side effects than exenatide.

There are many factors to consider when choosing a therapeutic regimen for a type 2 diabetes patient; for instance, efficacy, side effects, how many doses are required per day, cost to the patient and the odds that the patient will be adherent to therapy. Glucagon-like peptide-1 (GLP-1) receptor agonists are an attractive treatment choice for type 2 patients due to low risk of hypoglycemia combined with effective glycemic control and the added benefit of weight loss.

Liraglutide (Victoza©) and exanatide (Byetta©) are two options commonly prescribed, which raises the question of which is better. In a head-to-head trial between liraglutide 1.8mg once daily versus exenatide 10µg twice daily, liraglutide led to greater reductions in HbA1c. However, there have been no head-to-head trials comparing liraglutide 1.2mg once daily to exenatide 10µg twice daily. A recent meta-analysis was conducted to settle the matter.

The primary outcome of the current meta-analysis was the efficacy and tolerability of liraglutide 1.2mg and exenatide 10µg. In September 2012 and again in June 2015, a systemic literature search of MEDLINE, EMBASE, Current Contents, BIOSIS, PubMed, the Cochrane Library, National Institutes of Health Clinical Trials and Australian New Zealand Clinical Trials Registry was undertaken to identify trials of liraglutide 1.2mg once daily and exenatide 10µg twice daily. Studies included in the analysis had to be randomized, controlled trials with an intention-to-treat protocol in which the comparators for each drug were the same, (i.e. sulfonylurea, dipeptidyl-peptidase 4 inhibitor, thiazolidinedione, or placebo). The following criteria were analyzed in each study: proportion of patients with nausea and duration of nausea within the first 3 months of treatment, hypoglycemic events, discontinuation of treatment, mean change from baseline HbA1c, and fasting plasma glucose (FPG).

To measure the indirect comparison between outcomes, the mean difference between the active therapy and placebo was calculated from each study. By using placebo add-on therapy as a common reference, researchers were able to make an indirect comparison between liraglutide vs. exenatide add-on therapy and calculate the difference between the two means. Similar methods were used to calculate the means for the other outcomes. Post-hoc analysis was conducted to determine the duration of nausea. Statistical significance was determined by use of a 2-sided 95% confidence interval with a p value of <0.05 conferring significance. Review Manager was used to perform the analysis, which fit random effects models for the variance between placebo and active treatment, while also accounting for the heterogeneity between studies.

After review of studies for inclusion and exclusion criteria, 3 liraglutide and 10 exenatide trials were included in the final meta-analysis. It was found that liraglutide and exenatide significantly reduced mean HbA1c levels in patients with type 2 diabetes. However, the HbA1c was lowered from baseline significantly more than exenatide: -0.29%, 95% CI: -0.53 to -0.05, p=0.01. Likewise, fasting plasma glucose was significantly lower in the liraglutide and exenatide groups when compared to placebo, however liraglutide represented a significantly greater reduction than exenatide: -0.92mmol/L, 95% CI: -1.43 to -0.41, p<0.001. There was no statistical difference in overall adverse events between study drugs, including hypoglycemic events and nausea. Significantly fewer patients withdrew from treatment with liraglutide than with exenatide: odds ratio =0.34, 95% CI: 0.22 to 0.52, p<0.001.

Note:  A 30-day supply of liraglutide, at the dose in question, is over $200 less expensive than exenatide (according to GoodRx); there is a fairly strong case for improved patient adherence. It should, however, be noted that this study was funded by Novo Nordisk Pharmaceuticals, the producer of liraglutide, which does not diminish the findings of this study, but it may have introduced some level of bias into the selection of study drugs.

In conclusion, liraglutide 1.2mg once daily appears to decrease HbA1c and fasting plasma glucose significantly better than exenatide 10µg twice daily, with no difference in adverse events. Liraglutide has the added benefit of once-daily injection compared to twice daily with exenatide.

Practice Pearls:

  • Liraglutide 1.2mg once daily appears to significantly decrease HbA1c better than exenatide 10µg twice daily.
  • Liraglutide 1.2mg once daily appears to significantly decrease fasting plasma glucose significantly better than exenatide 10µg twice daily.
  • Liraglutide is less expensive than exenatide and requires only once daily injection, which may help with patient adherence (GoodRx).

Researched and prepared by Devon Brooks, Doctor of Pharmacy Candidate from LECOM College of Pharmacy, reviewed by Dave Joffe, BSPharm, CDE

 

Twigg S, Daja MM, O’Leary BA, Et al. “Once-daily liraglutide (1.2mg) compared with twice-daily exenatide (10µg) in the treatment of type 2 diabetes patients: an indirect treatment comparison meta-analysis.” Journal of Diabetes. (2016)Jan:1-29. Print.