This trial is investigating the long-term efficacy and safety of oral semaglutide, which is currently available on the market as Novo Nordisk’s subcutaneous (SC) injectable formulation, Ozempic.
The PIONEER 1 (26 weeks), 2 (52 weeks) and 3 (78 weeks) trials specifically investigated the long-term efficacy and safety of oral semaglutide in comparison to the placebo, Eli Lilly’s Jardiance (empagliflozin) 25mg, and Merck’s Januvia (sitagliptin) 100mg, respectively. The two comparators are commonly prescribed oral therapies for Type 2 diabetes (T2D).
It is highly advantageous for oral semaglutide to prove that it has significantly greater efficacy and a stronger safety profile in comparison to popular T2D treatments, to achieve a competitive advantage. Increasingly, patient compliance is a challenge in the diabetes space due to the frequency of medication use and the need to subcutaneously inject some of the medications. Oral semaglutide provides significant promise to improving compliance, as it will be the first available glucagon-like peptide-1 receptor agonist (GLP-1 RA) on the market, if approved.
Each PIONEER trial consisted of similar baseline characteristics, with all individuals ages 55–58 years with approximately 32–33kg/m2 body mass index (BMI) and 8.0–8.3% haemoglobin A1c (HbA1c). In the PIONEER 1 trial, which investigated oral semaglutide versus placebo, the change from baseline HbA1c (8.0%) to week 26 was recorded for the three doses as 0.8% for the 3mg dose, -1.3% for the 7mg dose, and -1.5% for the 14mg dose, with -0.1% for placebo. The proportion of subjects that achieved HbA1c of under 7.0% at 26 weeks was also recorded from baseline 8.0%, at 59% for the 3mg dose, 72% for the 7mg dose, 89% for the 14mg dose, and 34% for placebo.
Bodyweight change from baseline (88.8kg) was also recorded for the three doses as -1.7kg for the 3mg dose, -2.5kg for the 7mg dose, and -4.1kg for the 14mg dose, as well as -1.5kg for placebo. In the PIONEER 2 trial, which investigated oral semaglutide versus Jardiance 25mg, the change from baseline HbA1c (8.1%) to week 52 was recorded for both study arms as -1.3% for 14mg oral semaglutide and -0.8% for Jardiance 25mg. The proportion of subjects who achieved HbA1c under 7.0% at 52 weeks was also recorded from baseline 8.1% as 72% with 14mg oral semaglutide and 42% with Jardiance 25mg. Body weight change from baseline (91.6kg) was also recorded as -4.kg for 14mg oral semaglutide and -3.8kg for Jardiance 25mg.
Finally, for the PIONEER 3 trial, which investigated oral semaglutide at the three doses (3mg, 7mg, and 14mg) versus Januvia 100mg, the change from baseline HbA1c (8.3%) to week 78 was recorded for all doses of both study arms. For the three doses of oral semaglutide, the change from baseline was -0.3% for the 3mg dose, -0.7% for the 7mg dose, and -1.1% for the 14mg dose, with -0.4% for Januvia 100mg. The proportion of subjects that achieved HbA1c under 7.0% was recorded from baseline (8.3%) as 33% for the 3mg dose, 50% for the 7mg dose, 52% for the 14mg dose, and 39% for Januvia 100mg. Body weight change from baseline (91.2kg) was also recorded as -1.9kg with the 3mg dose, -2.7kg with the 7mg dose, -3.5kg with the 14mg dose, and -1.1kg with Januvia 100mg. Across all three PIONEER trials, 55–58% of subjects suffered from an adverse event (AE), the most common of which was nausea at the 14mg dose; this AE is commonly associated with the GLP-1 RA drug class.
Once-daily oral semaglutide demonstrated a significant dose-dependent glucose-lowering effect compared to placebo and the active comparators (Jardiance and Januvia). Oral semaglutide also provided a significant dose-dependent reduction in body weight versus placebo and the active comparators. Finally, across all three PIONEER trials, no unexpected safety findings were observed.
GlobalData believes that Novo Nordisk will gain an increased share of the T2D oral therapy market, pending the successful approval of oral semaglutide.
GlobalData (2019). Type 2 Diabetes – Global Drug Forecast and Market Analysis to 2028, to be published
GlobalData (2018). Type 2 Diabetes: Competitive Landscape to 2026, March 2018, GDHC004CL