A Significant Effect of Oral Semaglutide on Cardiovascular Risk Factors in Patients With Type 2 Diabetes

Yanai, Hidekatsu; Hakoshima, Mariko; Adachi, Hisashi; Katsuyama, Hisayuki

doi:10.14740/cr1441

Cited by 16 publications

(22 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the PIONEER 6 trial, low-density lipoprotein (LDL)-cholesterol and triglyceride levels were modestly lower in the oral semaglutide group, 21 while in other studies, a significant decrease in LDL-cholesterol and non-high-density lipoprotein-cholesterol was observed during oral semaglutide treatment. 20 In the study by Dahl et al., 22 a significant decrease in very low-density lipoproteins, apolipoprotein B48, and triglycerides was observed after 12 weeks of treatment with oral semaglutide at a dose of 14 mg daily.…”

Section: Discussionmentioning

confidence: 94%

“…No significant effect on blood pressure values was observed during oral semaglutide treatment in the present study, although initial values were in the range of hypertension; this contrasts with the results of some other studies, where significant decreases in systolic blood pressure values were observed. 20,21 In the analysis of all PIONEER studies, blood pressure remained similar, or was slightly reduced over time, in patients treated with oral semaglutide compared with active comparators. 7 In addition, the present study did not reveal significant effects of oral semaglutide on lipid parameters.…”

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience

Janić,

Jovanović,

Janež

et al. 2023

J Int Med Res

View full text Add to dashboard Cite

Objective To explore the effects of oral semaglutide on glycaemic parameters, body weight, and satisfaction in the first recipient patients with type 2 diabetes mellitus in Slovenia, in a real-world clinical practice setting. Methods The first consecutive adult patients with type 2 diabetes who were eligible for oral semaglutide treatment were included in this prospective, open-label interventional study. Patients received increasing doses of oral semaglutide and were evaluated at inclusion, at 1 month, then 3–5 months after starting treatment. Fasting blood glucose, glycosylated haemoglobin (HbA1c), body weight, patient satisfaction with oral semaglutide treatment (using the validated Treatment Satisfaction Questionnaire for Medication), and adverse effects, were analysed. Statistical analyses were performed using one-way analysis of variance, and, when significant interactions were found, Bonferroni post-hoc test. A P-value <0.05 was considered statistically significant. Results Twenty patients (11 male: 9 female; mean age, 59.9 ± 1.5 years; mean diabetes duration, 8.5 ± 1.4 years) were included. Oral semaglutide (7 and 14 mg) significantly decreased HbA1c (from 9.4 ± 0.3% to 8.2 ± 0.2% and 7.8 ± 0.2%, respectively) and fasting plasma glucose (from 11.2 ± 0.5 mmol/L to 9.2 ± 0.7 mmol/L and 8.9 ± 0.4 mmol/L, respectively). Oral semaglutide (14 mg) significantly decreased body weight (from 100.9 ± 2.7 kg to 92.7 ± 2.4 kg). Patients reported that treatment was easy to use and expressed high global satisfaction. Mild and transient, mostly gastrointestinal, adverse effects were reported in 10 patients. Conclusions Oral semaglutide, the first oral glucagon-like peptide 1 receptor agonist, was effective and safe, and associated with high patient satisfaction, in its first recipients in Slovenia. The results are important for daily clinical practice involving patients with type 2 diabetes, however, due to the small study population, lack of placebo control, and short exposure to oral semaglutide, the effectiveness of oral semaglutide in clinical practice requires further investigation.

show abstract

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 98%

Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience

Janić,

Jovanović,

Janež

et al. 2023

J Int Med Res

View full text Add to dashboard Cite

show abstract

“…While there is still no significant evidence that oral semaglutide can reduce the rates of cardiovascular events in people with T2D, this finding may rely on a supposed “class effect” of GLP-1RA in protecting from cardiovascular disease [ 20 ]. In addition, oral semaglutide can improve cardiovascular risk factors [ 6 ], and a pooled analysis of the SUSTAIN-6 and PIONEER-6 trials identified a strong consistency in the effects on cardiovascular outcomes of injectable and oral semaglutide [ 21 ]. The effects of oral semaglutide on cardiovascular outcomes in individuals with T2D and established atherosclerotic cardiovascular disease and/or chronic kidney disease are being tested in the SOUL trial [ 9 ], the results of which are expected to be presented in 2025.…”

Section: Discussionmentioning

confidence: 99%

“…Treatment of patients with T2D with oral semaglutide results in an improvement of cardiovascular risk factors [ 6 ]. Although there is still no evidence that oral semaglutide improves cardiovascular outcomes of T2D, the same active compound, when administered subcutaneously in the SUSTAIN-6 trial, reduced the rate of 3-point major adverse cardiovascular events (3P-MACE) compared to placebo [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Morieri,

Candido,

Frontoni

et al. 2023

Diabetes Ther

View full text Add to dashboard Cite

Introduction This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42% < 5 years), and a minority (15.6%) had a history of cardiovascular events. Importantly, oral semaglutide was started in subjects with various disease durations and background therapies. Notably, its initiation was accompanied by de-prescription of sulfonylureas, pioglitazone, DPP-4 inhibitors, and insulin. Choice of oral semaglutide was influenced by patient profiles and ongoing glucose-lowering regimens. Factors such as younger age, higher HbA1c, and ongoing SGLT-2 inhibitor therapy drove the choice of oral semaglutide with the aim of improving glycemic control. Projected glycemic effectiveness analysis revealed that oral semaglutide could potentially lead HbA1c to target in > 60% of patients, and more often than sitagliptin or empagliflozin. Conclusion The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-023-01490-6.

show abstract

“…On the other hand, one also needs to consider other possible indirect influences that orally administered butyrate may have on serum lipids, for example by stimulating the secretion of glucagon-like peptide 1 (GLP-1) [ 24 , 25 ]. The latter is an established enhancer of β cell function and insulin secretion [ 24 , 25 ], but there is also emerging evidence that GLP-1 agonists can lower serum LDL-C [ 26 , 27 ]. Therefore, while our in vitro studies give insights into the possible effect of butyrate on hepatic lipid metabolism in an in vitro setting, the question of whether butyrate can have beneficial effects on plasma lipids ultimately requires in vivo studies.…”

Section: Discussionmentioning

confidence: 99%

Butyrate Lowers Cellular Cholesterol through HDAC Inhibition and Impaired SREBP-2 Signalling

Bridgeman

Woo

Newsholme

et al. 2022

IJMS

View full text Add to dashboard Cite

In animal studies, HDAC inhibitors such as butyrate have been reported to reduce plasma cholesterol, while conferring protection from diabetes, but studies on the underlying mechanisms are lacking. This study compares the influence of butyrate and other HDAC inhibitors to that of statins on cholesterol metabolism in multiple cell lines, but primarily in HepG2 hepatic cells due to the importance of the liver in cholesterol metabolism. Sodium butyrate reduced HepG2 cholesterol content, as did sodium valproate and the potent HDAC inhibitor trichostatin A, suggesting HDAC inhibition as the exacting mechanism. In contrast to statins, which increase SREBP-2 regulated processes, HDAC inhibition downregulated SREBP-2 targets such as HMGCR and the LDL receptor. Moreover, in contrast to statin treatment, butyrate did not increase cholesterol uptake by HepG2 cells, consistent with its failure to increase LDL receptor expression. Sodium butyrate also reduced ABCA1 and SRB1 protein expression in HepG2 cells, but these effects were not consistent across all cell types. Overall, the underlying mechanism of cell cholesterol lowering by sodium butyrate and HDAC inhibition is consistent with impaired SREBP-2 signalling, and calls into question the possible use of butyrate for lowering of serum LDL cholesterol in humans.

show abstract

A Significant Effect of Oral Semaglutide on Cardiovascular Risk Factors in Patients With Type 2 Diabetes

Cited by 16 publications

References 13 publications

Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience

Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Butyrate Lowers Cellular Cholesterol through HDAC Inhibition and Impaired SREBP-2 Signalling

Contact Info

Product

Resources

About