Recent research published in the journal Diabetes Treatment We describe the results of the PIONEER REAL study, conducted in the Netherlands, which evaluated the effectiveness of oral semaglutide in managing type 2 diabetes and supporting weight loss.
study: PIONEER REAL Real-world use of oral semaglutide in adults with type 2 diabetes in a Dutch multicentre prospective observational study. Image credit: Davor Geber / Shutterstock.com
background
It is estimated that approximately 500 million people worldwide have type 2 diabetes in 2021. The incidence of type 2 diabetes is expected to continue to rise, with researchers predicting that approximately 700 million people will be diagnosed with the disease by 2045.
In the Netherlands, an estimated 1.1 million people will have diabetes in 2021, of whom more than 90% will be diagnosed with type 2 diabetes. Due to this high prevalence, type 2 diabetes costs the Netherlands 1.3 billion euros per year.
The Dutch Diabetes Federation recommends a stepwise introduction of diabetes treatment based on glycated hemoglobin (HbA1c) levels: treatment is usually started with metformin and sulfonylureas in sequence, followed by insulin, glucagon-like peptide-1 receptor agonists (GLP-1RAs), or dipeptidyl peptidase-4 (DPP-4) inhibitors.
Semaglutide is a GLP-1 analogue that is currently available as a daily subcutaneous injection and as an oral formulation. In addition to diet and exercise, semaglutide has been shown to effectively manage blood glucose levels in people with type 2 diabetes and reduce the risk of cardiovascular complications such as hypertension and inflammatory responses.
The approval of semaglutide in the Netherlands was based on results from the Phase 3 PIONEER clinical trial. To provide additional data supporting the use of once-daily oral semaglutide, the PIONEER REAL programme was subsequently launched in various countries in Europe, North America, the Middle East and East Asia. Specifically, PIONEER REAL aims to compare the efficacy of oral semaglutide with other injectable glucose-lowering medications in adults with type 2 diabetes.
About the Research
The PIONEER REAL study was conducted in 27 centers across the Netherlands from November 2020 to December 2022. All study participants were aged 18 years or older, had been diagnosed with type 2 diabetes, and had never been treated with injectable hypoglycemic drugs, except for short-term insulin.
The primary endpoint of the study was to assess the change in HbA1c levels from baseline to the end of the study, and secondary endpoints included change in weight. Study participants were also provided with a questionnaire-based assessment of their treatment satisfaction.
Characteristics of study participants
A total of 187 patients were included in the current study and received oral semaglutide once daily for 34 to 44 weeks. The mean age of the study cohort was 58 years, of which 54% were male and 88% were white. The mean duration of having diabetes was 8.7 years.
The mean weight was 103.1 kg, and the mean waist circumference and BMI (body mass index) were 118.1 cm and 35.1 kg/m2, respectively.2Each.
Study participants were taking an average of 1.6 and 2.4 different diabetes medications at the start and end of the study, respectively. Oral semaglutide was not among these medications. About 10% of participants reported not taking any glucose-lowering medications at the start of the study.
Approximately 98% of participants received 3 milligrams (mg) of oral semaglutide and 2% received 7 mg of oral semaglutide, with a median treatment duration of 37.7 weeks.
Therapeutic efficacy of oral semaglutide
Patients who received oral semaglutide experienced a significant reduction in HbA1c levels, from 8.6% at baseline to 7.3% at the end of the study.
About 8% of study participants had HbA1c levels below 7% at baseline. At the end of the study period, 48% of participants had HbA1c levels below 7%.
A weight loss of 5.8 kg was observed after semaglutide treatment. Of note, the effect of oral semaglutide treatment on HbA1c and weight was not significantly different between patients treated by diabetologists and those treated by non-diabetologists.
Participants treated with semaglutide were significantly more satisfied with their treatment, with 26.1% and 55.4%, respectively, reporting that taking semaglutide was easy or very easy.
By the end of the study, approximately 79% of participants were being treated with oral semaglutide, with a mean dose of 10.6 mg. More specifically, 53.7%, 42.2% and 4.1% were receiving 14 mg, 7 mg and 3 mg, respectively.
Safety Profile
A total of 246 mild to moderate side effects were reported in 58% of patients receiving oral semaglutide. Ten severe side effects were observed in 4.8% of participants, with one case of cholecystitis and one case of anal abscess considered related to oral semaglutide treatment.
The most frequently reported side effect was gastrointestinal discomfort, experienced by approximately 45% of study participants, which is similar to that observed with other GLP-1RAs. Side effects that led to discontinuation of semaglutide treatment included nausea, vomiting, and diarrhea.
One cardiac death occurred during the study period, but this event was thought to be unrelated to semaglutide treatment.
Journal References:
- Van Houtham, W., Schlomges, P., Amadid, H., etc (2024). Real-world use of oral semaglutide in adults with type 2 diabetes in the PIONEER REAL Dutch multicentre prospective observational study. Diabetes Treatment. doi:10.1007/s13300-024-01588-5, https://link.springer.com/article/10.1007/s13300-024-01588-5
