Both the intention-to-treat and on-treatment principles reported significant blood sugar reductions from the oral GLP-1 analogue.
Vanita Aroda, MD
Newly published findings from the PIONEER 1 phase 3a trial indicate that in comparison with placebo, once-daily oral semaglutide was associated with significant reductions in blood sugar in adults with type 2 diabetes.
The PIONEER 1 trial implemented 2 approaches to the evaluation—an intention-to-treat principle to explore the treatment effect (including that of rescue medications), and an on-treatment principle to observe the effect while on the trial product and without the use of rescue medications.
Announced at the American Diabetes Association’s 78th Annual Scientific Sessions in Orlando, Florida, the data was gathered in an evaluation of the Novo Nordisk glucagon-like peptide-1 (GLP-1) analogue’s safety and efficacy in doses of 3 mg, 7 mg, and 14 mg as monotherapy over the course of 26 weeks. The trial randomized 703 patients 1:1:1:1 to the 1 of the 3 doses of semaglutide or placebo.
With its intention-to-treat principle, the primary objective was achieved, with semaglutide showing that patients treated with any of the trio of doses achieved significant A1C reductions compared to placebo (P <.001 for all). Additionally, those administered the 14-mg dose of oral semaglutide achieving significant weight reductions compared to placebo (P <.001). The 7-mg and 3-mg doses did not reach statistical significance in weight loss.
“Despite advancements in the diabetes treatment landscape, many people with type 2 diabetes still struggle to reach their A1C target,” said Vanita Aroda, MD, the associate director of diabetes clinical research, at Brigham and Women’s Hospital in Boston, Massachusetts, in a statement. “Based on the first results of PIONEER, I am optimistic about the potential of having an oral GLP-1 receptor agonist that may help patients achieve their A1C and blood sugar goals.”
In the application of the on-treatment principle, the oral therapy resulted in A1C reductions of 0.8%, 1.3%, and 1.5% from the baseline mean of 8.0% for the 3-, 7-, and 14-mg doses, respectively, in comparison with placebo, which saw a reduction of 0.1% (P <.001 for all).
Moreover, of the total patient population in the semaglutide arm, 59%, 72%, and 80% of patients on respective doses of 3, 7, and 14 mg achieved the American Diabetes Association’s treatment target A1C level of <7.0% (P <.001). Comparatively, of those administered placebo, only 34% hit the target A1C goal.
The on-treatment principle examination also reported weight loss of 1.7 kg, 2.5 kg, and 4.1 kg in the 3-, 7-, and 14-mg dose arms, respectively, compared to 1.5 kg with placebo (P <.001 for 14 mg; P <.05 for 7 mg). Although, the 3-mg arm did not achieve a statistically significant weight difference.
Additionally, 21%, 29% and 44% of patients treated with oral semaglutide achieved a weight reduction of ≥5% compared to 16% with placebo.
The most common adverse event, occurring at a rate of greater than 5%, was nausea—5% to 16% with semaglutide, 6% with placebo—though its occurance diminished over time. Adverse events as a whole were reported by 58% of those in the 3-mg arm, 53% of those in the 7-mg arm, and 57% of the 14-mg arm, compared with 56% of those taking placebo. Treatment was discontinued due to adverse events in 2% to 7% of those on oral semaglutide and 2% of those given placebo.
Additional data from the PIONEER program, from the phase 3a PIONEER 4 and PIONEER 7, displayed that the therapy fared better in treating symptoms of diabetes than that of liraglutide (Victoza) and sitagliptin (Januvia). The pair of studies from reported that oral GLP-1 analogue was capable of greater body weight reduction and glycated hemoglobin reduction versus its competitors in adults with type 2 diabetes.
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