Oral semaglutide delivers real-world drops in blood sugar and weight in diabetes trial

By Tarun Sai LomteReviewed by Susha Cheriyedath, M.Sc.Nov 18 2025

New real-world evidence from the Netherlands shows that oral semaglutide meaningfully improves blood sugar and body weight in routine diabetes care, confirming clinical trial benefits in everyday practice.

Study: Real-world evaluation of clinical outcomes in Dutch patients with type 2 diabetes treated with oral semaglutide: A retrospective, observational cohort study using the PHARMO data network. Image Credit: zimmytws / Shutterstock

In a recent study published in the journal Diabetes, Obesity, and Metabolism, researchers evaluated clinical outcomes with oral semaglutide treatment in type 2 diabetes (T2D) patients.

T2D Burden and Dutch Epidemiology

T2D is associated with a higher risk of chronic non-communicable diseases, including kidney and cardiovascular disease. T2D and its complications pose a significant burden to public health and the economy. Early diagnosis and treatment can help in diabetes control and delay or prevent complications. In the Netherlands, around 1.2 million individuals are estimated to have diabetes, with the cost of diabetes care being €1.3 billion in 2019.

Clinical Relevance of Oral Semaglutide

The European Medicines Agency has approved semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), as an adjunct to diet and exercise to improve glycemic control in adults with T2D. Prospective clinical trials demonstrated that oral semaglutide significantly reduced body weight and glycated hemoglobin (HbA1c) in more than 9,500 patients with T2D. However, real-world evidence beyond prospective settings is needed to assess the impact of semaglutide in routine clinical practice, where monitoring frequency may vary.

Real-World Cohort and Eligibility Criteria

In the present study, researchers retrospectively assessed clinical outcomes in patients with T2D treated with oral semaglutide. They used real-world data of GLP-1RA-naïve T2D patients in the Netherlands who initiated oral semaglutide treatment. At least six months of data with no evidence of use of GLP-1RA analogs before the index date (first date of oral semaglutide dispensing) were needed to ensure GLP-1RA-naïve status.

Data Sources and Inclusion Parameters

The PHARMO Data Network was accessed to obtain patient healthcare data. T2D patients with at least two dispensings of oral semaglutide during the indexing period (2020–2022) were included. Patients with less than 6 weeks of follow-up or overlapping subcutaneous and oral semaglutide treatments were excluded. Patients were followed up until 12 months, death, semaglutide discontinuation, or initiation of new anti-diabetic drugs post-index date.

Clinical Measures and Statistical Approach

Data on clinical parameters, including body weight, HbA1c, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and blood pressure (BP), were collected at baseline and at 3, 6, 9, and 12 months. Mixed-effect models for repeated measures were used to describe changes over time from baseline. Analyses were adjusted for age, sex, T2D duration, semaglutide dose, baseline endpoint level, index year (to account for reimbursement policy changes), and concomitant anti-diabetic treatment. Baseline values for lipids and blood pressure were derived from measurements taken up to 12 months before initiation, which may introduce some baseline variability. No safety endpoints were collected, consistent with the study’s observational design. The study was funded by Novo Nordisk, the manufacturer of semaglutide, and several authors are employees of the company.

Study Population and Baseline Characteristics

The researchers identified 932 T2D patients who had at least two dispensings of oral semaglutide between 2020 and 2022. Of these, 731 individuals were GLP-1RA-naïve and were included in the study. On average, patients were aged 62 and had T2D for about 11 years. At baseline, the mean body weight was 102 kg, HbA1c was 70 mmol/mol, TC was 4.32 mmol/L, LDL was 2.38 mmol/L, and HDL was 1.06 mmol/L.

Baseline Blood Pressure and Follow-Up Availability

Further, the baseline mean systolic (SBP) and diastolic BP (DBP) were 137 mmHg and 81 mmHg, respectively. Most patients (94%) initiated oral semaglutide at a dose of 3 mg/day. Patients used a variety of concomitant medications for T2D and cardiovascular disease. Based on the availability of baseline and at least one follow-up measurement, 320, 260, 155, 200, 155, and 297 patients were included in the analyses of HbA1c, body weight, TC, LDL, HDL, and BP, respectively. The authors noted that reduced access to primary care during the COVID-19 pandemic contributed to the large proportion of missing follow-up laboratory values.

HbA1c Reductions Across Follow-Up

Overall, the average follow-up duration was 5.8 months, with longer follow-up times in body weight (8.2 months) and HbA1c cohorts (8.1 months. At three months from baseline, the mean change in HbA1c was significant at -9.68 mmol/mol. Significant decreases in HbA1c (from baseline) continued at six, nine, and 12 months (-16.05 mmol/mol). Moreover, the proportion of patients achieving their personalized HbA1c target levels increased at each subsequent time point.

Body Weight Loss Over Time

Further, patients experienced significant reductions in body weight; the mean change in body weight from baseline was -2.93 kg at three months, -3.91 kg at six months, -4.88 kg at nine months, and -4.73 kg at 12 months. Minimal changes were observed in DBP and blood lipid parameters over 12 months. The mean change in TC from baseline was -0.31 mmol/L at three months, with similar smaller decreases at subsequent time points.

Blood Lipid and Blood Pressure Stability

The mean changes from baseline in HDL and LDL were smaller and non-significant at 12 months. DBP showed smaller mean changes from baseline, with the largest change noted at nine months (-2.36 mmHg). The mean changes from baseline in SBP ranged from -3.13 mmHg at six months to -4.38 mmHg at nine months.

Real-World Implications for Semaglutide

Taken together, GLP-1RA-naïve T2D patients in the Netherlands treated with oral semaglutide achieved significant reductions in body weight and HbA1c. Further, small changes in lipid parameters and DBP were noted over 12 months, with moderate improvements in SBP. Overall, these results provide evidence of consistent benefits in clinical measures with oral semaglutide treatment in real-world clinical practice settings despite substantial variability in available follow-up data.