The Effect of Oral Semaglutide on Cardiovascular Risk Factors in Patients with Type 2 Diabetes: A Systematic Review.

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.