Oral semaglutide provides real reductions in blood sugar levels and weight in a diabetes study

Oral semaglutide provides real reductions in blood sugar levels and weight in a diabetes study

New real-world evidence from the Netherlands shows that oral semaglutide significantly improves blood sugar and body weight in routine diabetes treatment, confirming the benefits of clinical trials in daily practice.

In a study recently published in the journalDiabetes, obesity and metabolismResearchers evaluated the clinical outcomes of oral semaglutide treatment in patients with type 2 diabetes (T2D).

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 represent a significant public health and economic burden. Early diagnosis and treatment can help control diabetes and delay or prevent complications. In the Netherlands, it is estimated that around 1.2 million people suffer from diabetes, with the cost of diabetes care amounting to 1.3 billion euros 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 blood sugar control in adults with type 2 diabetes. Prospective clinical trials showed that oral semaglutide significantly reduced body weight and glycated hemoglobin (HbA1c) in more than 9,500 patients with type 2 diabetes. However, real-world evidence that goes beyond prospective settings is needed to evaluate the impact of semaglutide in routine clinical practice, where monitoring frequency may vary.

Cohort and admission criteria from practice

In the present study, investigators retrospectively evaluated clinical outcomes in patients with type 2 diabetes treated with oral semaglutide. They used real-world data from GLP-1RA-naïve T2D patients in the Netherlands who started oral semaglutide treatment. To ensure GLP-1RA-naïve status, at least six months of data with no evidence of GLP-1RA analogue use prior to the index date (first date of oral semaglutide administration) were required.

Data sources and inclusion parameters

To obtain patient care data, the PHARMO data network was accessed. T2D patients with at least two doses of oral semaglutide during the index period (2020–2022) were included. Patients with a follow-up period of less than 6 weeks or overlapping subcutaneous and oral semaglutide treatments were excluded. Patients were followed until month 12, death, discontinuation of semaglutide, or initiation of new antidiabetic medications after the 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, 3, 6, 9, and 12 months. Repeated measures mixed-effect models were used to describe changes over time from baseline. Analyzes were adjusted for age, sex, T2D duration, semaglutide dose, baseline endpoint, index year (to account for changes in reimbursement policies), and concomitant antidiabetic treatment. Baseline lipids and blood pressure were derived from measurements taken up to 12 months before treatment initiation, which may result in some baseline variability. In keeping with the observational design of the study, no safety endpoints were collected. The study was funded by Novo Nordisk, the manufacturer of semaglutide, and several authors are employees of the company.

Study population and baseline characteristics

Researchers identified 932 T2D patients who received at least two doses of oral semaglutide between 2020 and 2022. Of these, 731 people were GLP-1RA naive and were included in the study. On average, patients were 62 years old and had suffered from T2D for approximately 11 years. At baseline, mean body weight was 102 kg, HbA1c 70 mmol/mol, TC 4.32 mmol/L, LDL 2.38 mmol/L and HDL 1.06 mmol/L.

Baseline blood pressure and follow-up availability

In addition, mean baseline systolic (SBP) and diastolic blood pressure (DBP) were 137 mmHg and 81 mmHg, respectively. Most patients (94%) started oral semaglutide at a dose of 3 mg/day. The patients took various concomitant medications for type 2 diabetes and cardiovascular disease. Based on the availability of the baseline measurement and at least one follow-up measurement, 320, 260, 155, 200, 155, and 297 patients were included in the analyzes of HbA1c, body weight, TC, LDL, HDL, and blood pressure, respectively. The authors found that limited access to primary care during the COVID-19 pandemic contributed to the large proportion of missing laboratory values ​​at follow-up.

HbA1c reductions during 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). Three months after baseline, the mean change in HbA1c was significant at -9.68 mmol/mol. The proportion of patients achieving their personalized HbA1c target values ​​increased at each subsequent time point.

Body weight loss over time

In addition, the patients experienced a significant reduction in body weight; The mean change in body weight from baseline was -2.93 kg after three months, -3.91 kg after six months, -4.88 kg after nine months and -4.73 kg after 12 months. Minimal changes in DBP and blood lipid parameters were observed over a 12-month period. The mean change from baseline in TC was -0.31 mmol/L at three months, with similarly smaller declines at subsequent time points.

Blood lipid and blood pressure stability

The mean changes from baseline in HDL and LDL were smaller and not significant at 12 months. DBP showed smaller mean changes compared to baseline, with the largest change noted at nine months (-2.36 mmHg). Mean changes in SBP from baseline ranged from -3.13 mmHg at six months to -4.38 mmHg at nine months.

Real-world implications for semaglutide

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

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