In a recent study published in the Journal of Clinical Medicine, a group of researchers described the clinical characteristics of patients with type 2 diabetes (T2D) initiating oral semaglutide and assessed its effects on glycemic control, body weight (BW), and tolerability in routine clinical practice.
Study: Oral Semaglutide in Routine Clinical Practice: Characteristics of People with Type 2 Diabetes Started on the Drug and Changes in Their Clinical Parameters after 24 Weeks of Treatment. Image Credit: luchschenF/Shutterstock.com
Background
Semaglutide is the first glucagon-like peptide-1 receptor agonist (GLP-1RA) available in an oral formulation.
Its efficacy in glycemic control, BW reduction, and safety have been consistently demonstrated in the Peptide Innovation for Early Diabetes Treatment (PIONEER) trials program, which includes ten randomized controlled trials involving 9,543 subjects with T2D.
The PIONEER program tested oral semaglutide across different stages of diabetes and various background treatments. Approved by the Food and Drug Administration (FDA) in 2019 and the European Medicines Agency (EMA) in 2020, it has been available in Italy since September 2021.
Further research is needed to evaluate the long-term cardiovascular outcomes and real-world effectiveness of oral semaglutide in diverse patient populations.
About the study
The present study was conducted in two Italian university-based diabetes centers using data from the Metaclinic/Medical Technology and Diagnostic Applications (METEDA) electronic chart system.
The local ethics committee approved the study, which included adults with T2D with documented glycated hemoglobin (HbA1c) and BW values before starting oral semaglutide. Exclusions were patients with type 1, secondary, or gestational diabetes or missing data.
Collected data included demographics, clinical measures, laboratory results, and treatment details. Microangiopathy was defined by complications like neuropathy or chronic kidney disease, while macroangiopathy included conditions like stroke or myocardial infarction.
Oral semaglutide was initiated with a 4-week dose-escalation regimen, starting at 3 mg, followed by 7 mg, and increasing to 14 mg if tolerated.
Patients were advised on drug management, including minimal water intake and timing relative to meals. Follow-up at six months recorded updated HbA1c, BW, adverse events, and reasons for discontinuation.
Statistical analysis used longitudinal linear mixed models to assess trends over time in various endpoints, with results expressed as mean changes from baseline with 95% confidence intervals.
Mean changes in HbA1c and BW were assessed overall and stratified by diabetes duration, sex, age, baseline body mass index (BMI), baseline estimated glomerular filtration rate (eGFR), and prior dipeptidyl peptidase four inhibitors (DPP4i) use.
Tercile analysis based on baseline HbA1c and BW examined their impact on follow-up outcomes. Significance was set at p <0.05 and analyzed using SAS software.
Study results
The study included 192 Caucasian patients with T2D prescribed oral semaglutide between September 2021 and December 2022. Of these, 44% were women, with a median age of 67 years and a median diabetes duration of 9 years.
The mean HbA1c was 7.9%, and the median fasting glucose was 146 mg/dL. Most were on glucose-lowering therapies like metformin (87%) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) (37.5%).
Common comorbidities included dyslipidemia (65%), hypertension (63%), and obesity (47%). Chronic complications involved macroangiopathy (31%) and microangiopathy (35%). Concomitant medications primarily included statins (53%) and antihypertensive agents.
Out of 192 patients, 12 discontinued oral semaglutide before the first follow-up due to early interruption. Effectiveness analysis was conducted on 180 subjects. After six months, the mean change in HbA1c was −0.68%, and the mean change in BW was −2.63 kg.
Stratifying the cohort by baseline HbA1c levels revealed the greatest reduction in those with the highest baseline levels. There were no significant variations in BW reduction across different baseline weight categories.
45% of participants achieved an HbA1c target below 7%, and 34% achieved a BW loss greater than 5%. The composite outcome of HbA1c levels below 7% and a weight loss greater than 5% was achieved by 22.5% of participants.
Stratification by disease duration showed a greater reduction in HbA1c in those with a shorter duration of diabetes. Effective HbA1c reduction was also observed across age groups, BMI categories, and eGFR levels, with a trend toward greater reduction in males.
Additionally, waist circumference (WC), lipid profile, and blood pressure improvements were observed. WC reduced by 2.1 cm, total cholesterol decreased by 17.41 mg/dL, and low-density lipoprotein cholesterol (LDL) decreased by 17.89 mg/dL.
Liver enzymes remained within normal limits, and blood pressure showed a non-significant reduction. Renal function and microalbuminuria remained unchanged.
Regarding glucose-lowering therapy, sulfonylureas and DPP4i were discontinued in all users, while using pioglitazone, SGLT2 inhibitors, and insulin remained largely unchanged.
All patients started with a 3 mg dose of oral semaglutide, with 93% increasing to 7 mg daily by the 6-month follow-up. Only 2% reached the maximum dosage of 14 mg per day.
No severe hypoglycemic episodes were reported. During the follow-up, 40 patients (20.8%) discontinued treatment, with gastrointestinal side effects being the main reason (13.5%), followed by limited effectiveness (5.2%). No gender differences were observed in terms of side effects or discontinuation rates.
Conclusions
In the study, patients with T2D starting oral semaglutide showed significant HbA1c and weight improvements after six months, especially those with a recent diabetes diagnosis. Approximately 25% achieved HbA1c levels ≤ 7% and >5% weight loss. The therapy also improved cardiovascular risk factors despite a 20.8% discontinuation rate due to gastrointestinal side effects.
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