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Semaglutide Beats Dulaglutide in Head-to-Head Trial

Semaglutide trumps Trulicity in most recent trial.

GLP-1 agonists have multiple physiological effects making them an enticing treatment option for patients with type 2 diabetes. By increasing insulin secretion and inhibiting glucagon release only in the presence of elevated glucose levels GLP-1 agonists can lower blood glucose while minimizing the chances of hypoglycemic events. Because of their effect on gastric emptying, patients often report a decrease in appetite, feelings of satiety and weight loss after beginning treatment. Preclinical studies also reported that GLP-1 agonists may promote β-cell proliferation and impede β-cell apoptosis, another attractive quality in this class of medication. There are several GLP-1 agonists available on the market today, but Eli Lilly’s Trulicity (dulaglutide) has been a popular and effective treatment choice for many practitioners since its approval in September, 2014. However, Novo Nordisk recently announced the results of the SUSTAIN-7 Trial, a Phase III study comparing the safety and efficacy of semaglutide against Trulicity, and the results may very well knock Trulicity off its pedestal.

SUSTAIN-7 is a randomized, parallel study that recruited over 1,200 participants for a 40-week trial in which participants either received 0.5 mg/week or 1 mg/week of semaglutide or 0.75 mg/week or 1.5 mg/week of Trulicity in addition to their current metformin regimen. All participants were at least 18 years of age, had an HbA1c between 7.0% – 10.5% and were required to be on at least 1,500 mg/day of metformin for the last 90 days. Participants were excluded if they were on any other antidiabetic regimens over the last 90 days, except metformin, or were on insulin within 2 weeks of beginning the trial. The primary outcome was change in HbA1c from baseline to week 40. Secondary outcomes included: change in body weight, change in fasting blood glucose, change in blood pressure, achieving an HbA1c equal to or below 6.5%, and any changes in the patient treatment satisfaction questionnaire.

To address the primary outcome the results were as follows: Patients taking 0.5 mg/week of semaglutide saw an HbA1c reduction of 1.5%, and patients taking 1 mg/week of semaglutide saw an HbA1c reduction of 1.8%. This was 0.4% higher than Trulicity’s HbA1c reduction where patients taking 0.75 mg/week saw an average HbA1c reduction of 1.1% and patients taking 1.5 mg/week saw an HbA1c reduction of 1.4%. In addressing secondary outcomes, the results were even more substantial. Patients taking semaglutide saw an average weight reduction of 4.6 kg for the lower dose and 6.5 kg on the higher dose. This was significantly more than Trulicity, with patients on the lower dose losing an average of 2.3 kg and patients on the higher dose losing an average of 3.0 kg. The American Diabetes Association current HbA1c goal is < 7% for most patients. Approximately 69% of participants taking 0.5 mg/week of semaglutide and 79% of participants taking 1mg/week of semaglutide met or surpassed this goal. These numbers were significantly higher than the Trulicity group with only 52% of patients taking 0.75 mg/week reaching that goal. Few patients achieved the stricter ADA recommendation of < 6.5%, however, more of the patients who did reach that goal were taking semaglutide. The glycemic and weight loss profile for semaglutide looks promising, but what about its effect on cardiovascular events?

Last year, the SUSTAIN-6 trial aimed to evaluate the cardiovascular outcomes in patients taking semaglutide versus placebo. This randomized, double-blinded, placebo-controlled trial demonstrated that patients taking semaglutide had a significant reduction in non-fatal myocardial infarction and stroke versus placebo, and reduced cardiovascular events by an estimated 26%. Novo Nordisk has proven through the SUSTAIN trials that semaglutide could be a top contender in the GLP-1 agonist market. While the FDA is still evaluating the use of this drug in patients with type 2 diabetes, the impressive safety and efficacy profile certainly helps make its case.

Practice Pearls:

  • Semaglutide reduced HbA1c more than Trulicity (1.8% vs. 1.4% on higher doses)
  • Semaglutide reduced weight more than Trulicity (6.5 kg vs. 3 kg on higher doses)
  • Semaglutide reduced the risk of myocardial infarction and stroke

References:

Garber, Alan J. “Long-Acting Glucagon-Like Peptide 1 Receptor Agonists: A review of their efficacy and tolerability.” Diabetes Care, American Diabetes Association, 1 May 2011, care.diabetesjournals.org/content/34/Supplement_2/S279. Accessed 21 Aug. 2017.

Caffrey, Mary. “Novo Nordisk’s Semaglutide Beats Dulaglutide on A1C, Weight Loss in Head-to-Head Trial.” AJMC, 18 Aug. 2017, www.ajmc.com/newsroom/novo-nordisks-semaglutide-beats-dulaglutide-on-a1c-weight-loss-in-head-to-head-trial. Accessed 21 Aug. 2017.

“Novo Nordisk’s Semaglutide Bests Trulicity in Diabetes Trial.” Managed Care Magazine Online, 17 Aug. 2017, managedcaremag.com/news/novo-nordisks-semaglutide-bests-trulicity-diabetes-trial. Accessed 21 Aug. 2017.

 

Jessica Lambert, University of South Florida College of Pharmacy, Doctor of Pharmacy Candidate 2018