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Comparisons of GLP-1 Agonists  

Mar 28, 2020
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Chardae Whitner, 2020 PharmD. Candidate, Lake Erie College of Osteopathic Medicine

Do any GLP-1 agonists provide better benefits than others?

Glucagon-like peptide-1 receptor agonists (GLP-1RA) have grown tremendously popular in the treatment of patients with type 2 diabetes. The growing popularity is a result of patients with type 2 diabetes achieving a more significant decrease in HbA1c. This study, designed as a retrospective real-world study conducted by Fadini et al., was seeking to determine the effectiveness of dulaglutide versus liraglutide and exenatide once weekly in patients with type 2 diabetes under routine care. Fadini stated the reasoning for this approach as, “Although randomized controlled trials provide the highest level of evidence to guide therapeutic decisions, real-world studies can address comparisons not covered by randomized controlled trials, can challenge randomized controlled trial findings and explore transferability to routine care settings.”  


GLP-1 REceptor agonists and real World evIdeNce (GLP-1REWIN), gathered data from diabetes specialist outpatient clinics in the Veneto region of Northeast Italy. Participants of the study were patients diagnosed with type 2 diabetes for at least one year, aged 18-80 years old. They had initiated dulaglutide, exenatide once weekly, or liraglutide from the time frame of 2010-2018.  Exclusions from this study included those patients who were previously on a GLP-1RA and switched to another or those patients who were on a fixed combination of GLP-1RA and basal insulin.  Less than 90 days before the baseline clinical and laboratory characteristics were collected, which included: age, sex, diabetes duration, body height and weight, body mass index, waist circumference, systolic and diastolic blood pressure, fasting plasma glucose, hemoglobin A1c, total cholesterol, HDL cholesterol, triglycerides, liver enzymes, serum creatinine, and urinary albumin excretion rate.   

Researchers assessed hemoglobin A1c, fasting plasma glucose, systolic blood pressure, and body weight when a GLP-1 receptor agonist was prescribed at the follow-up visit at the same clinic 3-13 months after baseline. From the participants in the study, 849 adults with type 2 diabetes were prescribed dulaglutide (Trulicity), 1,371 prescribed liraglutide (Victoza), and 198 prescribed once-weekly exenatide (Byetta). The average participant population was aged 60-62 years, 60-65% were males, diabetes duration was on average 9-10 years, baseline BMI 33-35 kg/m2 and hemoglobin A1c 8.2% 

Results from this real-life retrospective study found that participants taking dulaglutide experienced a 0.24% larger decrease in hemoglobin A1c (P = .003) and a 3.3 mm Hg more significant reduction of systolic blood pressure (= .01) at follow-up vs. those taking liraglutide in comparison to baseline measurements. However, it was discovered that participants taking dulaglutide achieved a 1 percentage point decrease in HbA1c from the baseline while those taking liraglutide achieved a 0.7 percentage point decrease.  

It was also evaluated that there was a nonsignificant difference between the groups in hemoglobin A1c decreases from baseline after propensity score matching participants taking dulaglutide with those taking exenatide. The researchers found that participants taking dulaglutide achieved a 1 percentage point decrease in hemoglobin A1c from baseline in comparison to those participants taking exenatide who achieved a 0.8 percentage point decrease from baseline.  

It was noted by researchers in an analysis comparing all three GLP-1RAs, data showed that dulaglutide appeared to provide more significant benefit than liraglutide and exenatide once weekly. The results, which were influenced by data, determined that there was a 0.19% larger decrease in hemoglobin A1c for those taking dulaglutide vs. those taking liraglutide (P = .003) and those taking exenatide once weekly (P = .007) in a meta-analysis of 149 studies.  

After the findings of this study, Fadini and colleges wrote this: “We confirmed our findings with a meta-analysis of similar observational studies that evaluated dulaglutide vs. liraglutide in the real world,” the researchers wrote. “However, these results do not inform on comparative drug potency, but highlight issues in transferring randomized controlled trial findings to clinical practice: Reaching the 1.8 mg emerges once more as a critical step to get the most from liraglutide therapy. In general, titration of GLP-1 receptor agonists may represent a barrier to the achievement of therapeutic goals.”  

Practice Pearls: 

  • Dulaglutide proved to have a more significant glycemic effect of patients with type 2 diabetes than liraglutide.  
  • There were similar effects of the dulaglutide and exenatide once weekly.   
  • Ithe final analysis, dulaglutide still showed to have a more significant benefit than both the liraglutide and exenatide once weekly. 

Morieri, Mario Luca, et al. “Effectiveness of Dulaglutide vs. Liraglutide and Exenatide Once-Weekly. A Real-World Study and Meta-Analysis of Observational Studies.” Metabolism, W.B. Saunders, 25 Feb. 2020, www.sciencedirect.com/science/article/abs/pii/S0026049520300548. 


Chardae Whitner, 2020 PharmD. Candidate, Lake Erie College of Osteopathic Medicine