A recent study published in the journal Diabetes Therapy reveals promising results from the PIONEER REAL study conducted in the Netherlands, showcasing the effectiveness of oral semaglutide in managing type 2 diabetes and aiding weight loss.
Background
In 2021, an estimated 500 million people globally were living with type 2 diabetes, a number projected to reach 700 million by 2045. In the Netherlands, approximately 1.1 million people had diabetes in 2021, with over 90% diagnosed with type 2 diabetes. This high prevalence incurs an annual cost of €1.3 billion for the country.
The Netherlands Diabetes Federation recommends a stepwise approach to diabetes treatment based on glycated hemoglobin (HbA1c) levels, starting with metformin and sulphonylureas, and progressing to insulin, GLP-1 receptor agonists (GLP-1RAs), or DPP-4 inhibitors.
Semaglutide, a GLP-1 analog, is available in both daily subcutaneous and oral forms. Alongside diet and exercise, it has been effective in managing blood glucose levels and reducing cardiovascular risks in type 2 diabetes patients. The approval of semaglutide in the Netherlands was based on phase three PIONEER clinical trial results. The PIONEER REAL program was subsequently launched across Europe, North America, the Middle East, and East Asia to further evaluate the efficacy of oral semaglutide compared to other injectable glucose-lowering medications.
The Study
Conducted between November 2020 and December 2022 at 27 sites in the Netherlands, the PIONEER REAL study involved adults over 18 years diagnosed with type 2 diabetes who had not been treated with injectable glucose-lowering drugs, except for short-term insulin. The primary endpoint was to assess changes in HbA1c levels from baseline to the study’s end, with secondary endpoints focusing on changes in body weight. Participants also completed treatment satisfaction questionnaires.
Participant Characteristics
The study included 187 patients who received once-daily oral semaglutide for 34-44 weeks. The average age of the participants was 58 years, with 54% being male and 88% White. The average duration of diabetes among participants was 8.7 years. Baseline measurements showed a mean body weight of 103.1 kilograms, a waist circumference of 118.1 cm, and a BMI of 35.1 kg/m2. At the study’s outset, participants were using an average of 1.6 antidiabetic medications, which increased to 2.4 by the end. Oral semaglutide was newly introduced to these regimens.
Therapeutic Efficacy
Participants receiving oral semaglutide showed a significant reduction in HbA1c levels, dropping from 8.6% at baseline to 7.3% at study’s end. Initially, only 8% of participants had HbA1c levels below 7%, but this figure rose to 48% by the study’s conclusion. Additionally, an average weight loss of 5.8 kg was recorded. These improvements were consistent regardless of whether participants were treated by diabetes or non-diabetes specialists.
Participants expressed high treatment satisfaction, with 26.1% and 55.4% finding semaglutide easy or very easy to consume, respectively. By the study’s end, 79% of participants continued using oral semaglutide, with the majority (53.7%) on a 14 mg dose.
Safety Profile
A total of 246 mild-to-moderate adverse effects were reported in 58% of participants, with ten severe adverse events occurring in 4.8% of participants. Gastrointestinal issues were the most common side effects, affecting about 45% of participants, similar to other GLP-1RAs. Nausea, vomiting, and diarrhea led to treatment discontinuation for some participants. One death due to a cardiac disorder occurred but was deemed unrelated to semaglutide treatment.
Overall, the study underscores the potential of oral semaglutide as an effective treatment for managing type 2 diabetes and promoting weight loss, offering a promising alternative to injectable medications.
