The Effect of Oral Semaglutide on Cardiovascular Risk Factors in Patients with Type 2 Diabetes: A Systematic Review
Bibliographic record
Abstract
Background/Objectives: There has been a prominent rise in the use of GLP-1 RAs recently, particularly semaglutide, for the treatment of T2DM with or without obesity. Subcutaneous injections of semaglutide have demonstrated beneficial effects on cardiovascular risk factors. However, several factors hinder the use of subcutaneous administration. Therefore, the oral route is preferred; yet, it remains unclear whether oral semaglutide provides cardiovascular protection comparable to its subcutaneous counterpart. Methods: A systematic review in line with the PRISMA guidelines was performed based on eight databases (Scopus, Proquest, Science Direct, PubMed, Google Scholar, EBSCOHost, Clinical Key, and The Cochrane Library) to identify clinical studies that assessed the effects of oral semaglutide on cardiovascular risk factors, especially blood pressure and lipid or cholesterol profile in T2DM patients. Inclusion criteria included studies that used oral semaglutide on top of a mainstay treatment for T2DM compared to the placebo control group, assessed cardiovascular risk factors, and were conducted prospectively or in an RCT design. Case reports, ongoing studies with incomplete results, reviews, animal studies, and retrospective studies were excluded. The Newcastle-Ottawa scale and Jadad scale were used to assess the risk of bias in the included studies. Data extracted from the selected studies included patient characteristics, study design, research methodology, intervention regimen, and cardiovascular risk factors: SBP, DBP, TC, HDL, LDL, and TG. Data were presented in a table format to compare and synthesize the results of each study. Results: Five clinical studies were selected (two were randomized trials and three were observational, prospective studies). All five studies reported a consistent trend in the reduction in SBP (ranging from −2.60 to −12.74 mmHg) after oral semaglutide treatment. However, its effect on DBP was found to be less consistent. Lipid profile results show the most consistent trend in total cholesterol reduction (−8.80 to −22.19 mg/dL). Four studies reported a favorable reduction in LDL cholesterol (−7.6 to −18.0 mg/dL) and triglycerides (−11.00 to −40.13 mg/dL). HDL cholesterol shows the least consistent findings where three studies reported an increasing trend, yet this was not statistically significant; one study reported a mild increase in HDL (+0.90 ± 0.12; p < 0.0001); and one study reported a slight reduction in HDL (55.6 ± 2.5 to 51.6 ± 2.2; p < 0.05). Conclusions: Once-daily oral semaglutide is a promising add-on therapy for the treatment of T2DM with or without obesity in reducing cardiovascular risk factors, potentially lowering cardiovascular-related mortality. Thus, once-daily oral semaglutide may offer cardiovascular benefits comparable to the subcutaneous form, with the advantage of improved adherence.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.019 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.010 | 0.008 |
| Bibliometrics | 0.006 | 0.007 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".