During the study period, 43 patients were switched from a conventional GLP-1 RA to semaglutide, and 7 patients were naïve to semaglutide; all patients agreed to be registered in the study. All 50 patients continued with semaglutide for at least the 6-month observation period. The following GLP-1 RAs were administered before semaglutide in 43 patients (switching to semaglutide group); dulaglutide in 24 patients (mean dose: 0.75 mg), liraglutide in 18 patients (1.60 ± 0.33 mg), and exenatide in 1 patient (10 μg). All 7 patients not receiving a GLP-1 RA before administration of semaglutide (naïve to semaglutide group) were treated with sodium-glucose cotransporter-2 (SGLT2) inhibitors. The dose of semaglutide after 6 months was 0.92 ± 0.19 mg in all patients.
Table 1 lists the characteristics of each group as well as the 50 patients treated with semaglutide. In the 50 patients, males composed 42.0% of the study group, and the mean age was 51.3 ± 11.0 years. Mean BMI was 32.2 ± 6.2 kg/m2, and insulin secretion was relatively preserved, as evaluated by C-peptide levels.
Changes in HbA1c and body weight
In 43 patients in switching to semaglutide group, HbA1c level decreased significantly, from 6.72 ± 0.62% at baseline to 6.45 ± 0.51% after 3 months (p < 0.01) and 6.22 ± 0.54% after 6 months (p < 0.01) as shown in Fig. 1. Similarly, body weight declined significantly, from 86.5 ± 18.8 kg to 84.7 ± 19.0 kg after 3 months (p < 0.01) and 82.7 ± 19.0 kg after 6 months (p < 0.01) (Fig. 2). The proportion of patients who achieved HbA1c < 6.5% at 6 months was 60.6%.
In the 7 semaglutide-naïve patients, HbA1c level decreased significantly, from 7.19 ± 1.21% at baseline to 6.36 ± 0.50% after 6 months (p = 0.04, Fig. 1). Body weight also declined significantly, from 95.3 ± 8.0 kg to 91.5 ± 7.2 kg (p = 0.02, Fig. 2). All 7 of these patients achieved HbA1c < 6.5% at 6 months.
Figure 3 shows the distribution of changes in body weight and HbA1c after 3 and 6 months. Decrease in both HbA1c and body weight were observed in 74% of patients after 3 months and 92% of patients after 6 months.
Changes in the dosage and administration of concomitant hypoglycemic agents
In 19 patients receiving insulin, the insulin dose was reduced by 7.9 ± 3.7 units by study end. In 6 patients receiving sulfonylureas or glinides, dose reduction (4 patients) or interruption (2 patients) was possible.
Factors associated with change in HbA1c
HbA1c level at baseline was significantly correlated with the change in HbA1c at 6 months after initiation of semaglutide (r = 0.696, p < 0.01). In addition, total cholesterol and triglyceride levels at baseline were significantly correlated with the change in HbA1c at 6 months (r = 0.312, p = 0.027 and r = 0.318, p = 0.03, respectively). There was no significant correlation between HbA1c change and body weight change at 6 months after initiation of semaglutide (r = 0.07).
Changes in metabolic parameters
Changes in uric acid, triglycerides, total cholesterol, HDL-C, and LDL-C are summarized in Table 2. Six months after switching to semaglutide, serum uric acid, total cholesterol, and triglyceride levels were significantly decreased. In the 50 patients, ACR was also significantly lower, declining from 14.0 (6.7, 22.8) mg/g·CRE at baseline to 10.2 (6.0, 23.1) mg/g·CRE after 6 months (p = 0.04).
Results of blood tests to evaluate adverse effects are summarized in Table 3. At 6 months after initiation of semaglutide, liver-related parameters (AST, ALT, γ-GTP, LDH) were significantly improved. There were no adverse events related to semaglutide except mild nausea or vomiting. No hypoglycemic events were reported during the observation period.