Oral semaglutide improves body composition and preserves lean mass in patients with type 2 diabetes: a 26-week prospective real-life study

Abstract

Background: Oral semaglutide is the first glucagon-like peptide-1 receptor agonist (GLP-1RA) designed for oral administration; it offers a promising opportunity to facilitate an early approach to Type 2 Diabetes (T2D). The study aimed to evaluate, in a real-life setting, the effects of oral semaglutide on the body composition of patients with T2D after 26 weeks of therapy.

Methods: Thirty-two patients with T2D were evaluated at baseline (T0) and after three (T3) and six (T6) months of therapy with oral semaglutide. At each time point, body composition was assessed using a phase sensitive bioimpedance analyzer. Clinical, anthropometric and laboratory parameters, and the main biometric surrogates of liver steatosis and fibrosis, were also analyzed and compared.

Results: A significant and early reduction in anthropometric and glucometabolic parameters, alanine aminotransferase, Fatty Liver Index, and Fat Mass was observed. Visceral Adipose Tissue (VAT) decreased, while Fat Free Mass and Skeletal Muscle Mass (SMM) were preserved during therapy, resulting in a beneficial increase in the SMM/VAT ratio. Finally, an overall improvement in body fluid distribution was observed.

Conclusion: Our real-world data confirm the clinical efficacy of oral semaglutide and highlight its ability to improve the nutritional status of patients with T2D.

Keywords: GLP-1RA; body composition; fat free mass; fat mass; oral semaglutide; skeletal muscle mass; type 2 diabetes; visceral adipose tissue.

Figure 1

The flow chart illustrates the process of selecting patients enrolled in the study.

Figure 2

Values are expressed as percent change from baseline (T0). The absolute values of each parameter at T0 are also indicated. Change versus T0: **p<0.001. BMI, Body Mass Index.

Figure 3

Values are expressed as percent change from baseline (T0). The absolute values of each parameter at T0 are also indicated. Change versus T0: **p<0.001. Change at T6 versus T3: #p<0.05. HbA1c, Glycated hemoglobin.

Figure 4

Mean changes, expressed as percentage changes from baseline (T0 = 100%). Change versus T0: *p<0.05; **p<0.001. eGFR, estimated Glomerular Filtration Rate; LDL, Low-Density Lipoprotein; HDL, High-density Lipoprotein; HOMA-IR, HOmeostasis Model Assessment of Insulin Resistance.

Figure 5

Values are expressed as percent change from baseline (T0). Change versus T0: *p<0.05; **p<0.001. FMI, Fat Mass Index; VAT, Visceral Adipose Tissue; FFMI, Fat Free Mass Index; SMI, Skeletal Muscle Mass Index; SMM, Skeletal Muscle Mass.

Figure 6

Distribution of major side effects complained by patients during treatment with oral semaglutide. Percentages are related to the total number of patients (n=32).

Figure 7

The graph highlights the occurrence of side effects during the observation period. Most of them occurred after at least one month of treatment, indicating that the dose adjustment of semaglutide (3 to 7 mg after 30 days of treatment) was the cause of these complaints. Meteorism was the most transient side effect, disappearing in 55 days. Dysgeusia is one of the latest classified side effects, as suggested by post-marketing data, and was recently included among the side effects of oral semaglutide by the European Medicines Agency. Dysgeusia was described early after two weeks of treatment (3 mg/day) and consisted of a metallic taste in the tongue and mouth, which occurred in only 6% of patients but persisted throughout observation.