Endocrine Abstracts

Introduction: It has been reported that patients with obesity and T2DM treated with oral semaglutide not only have a reduced total caloric input, but they also tend to reduce the proportion of fatty and sweet foodstuffs in an ad libitum diet. A modest improvement in the lipid profile of patients with obesity and T2DM treated with oral semaglutide has been reported, but its dependence on weight loss is not well established. We undertook to study the mediation effect of weight loss on the lipid profile changes in these patients.

Methods: We performed retrospective analyses of the lipid profiles of consecutive patients with obesity and T2DM who started oral semaglutide therapy. Data were obtained from the baseline visit and a successive visit, 3-5 months afterwards. Post-hoc mediation analyses were performed in order to quantify the relative contribution of weight loss in the lipid profile changes. Patients who started or changed lipid-lowering medication simultaneously, or refused informed consent were excluded. Data are given as mean ± sd.

Results: Data were obtained from 48 patients, 31 (65%) women, age 54.4 ± 11.8 years, T2DM duration 6.7 ± 2.7 years, BMI 36.6 ± 5.3 kg/m²; 43 (90%) had 14 mg semaglutide daily, 3 (6%) 7 mg, and 2 (4%) 3 mg. 29 (60%) of the patents were on statins,12 (25%) on fibrates and 4 (8%) on EPA/DHA supplements. The geometric mean of the total cholesterolemia at baseline was 167 mg/dl, variation coefficient 47%. For HDLc, LDLc and non-HDLc the values were 44 mg/dl, 58%; 82 mg/dl, 49%; 122 mg/dl, 52%, and 207 mg/dl, 68%. The changes in total cholesterol and its fractions (HDLc, LDLc, non-HDLc) were favorable but non-significant (-4.8%, +2,2%, -7.3%, -2.1%) while there was a significant reduction of triglyceridemia from its baseline value 207 ± 68 mg/dl (-17.6 ± 11.5%, P=0.021). The weight loss was -3.6 ± 1.5 kg (P=0.033). The reductions in weight and triglycerides were positively correlated (Pearson’s R: 0.29, P=0.0023). The mediation analyses showed that a reduction of 6.4 ± 7.3% in triglyceridemia was mediated by weight loss, but 11.2 ± 8.4% was independent of it.

Conclusions: In patients with T2DM and obesity, oral semaglutide significantly improved plasma triglycerides, with a non-significant improvement of total cholesterol and its fractions. The reduction of triglyceridemia was mediated only partially by weight loss, suggesting additional mechanisms, maybe including healthier dietary choices. Oral semaglutide may reduce the need for fibrates and EPA/DHA supplements.