Abstract
In this study, we investigated the effect of exenatide (EXE), a glucagon-like peptide (GLP)-1 receptor agonist, on kidney function, obesity indices, and glucose control in overweight/obese patients with type 2 diabetes mellitus (T2DM). A total of 159 overweight/obese patients with T2DM were randomized to the EXE group or insulin glargine (GLAR) control group for a total treatment period of 24 weeks. EXE intervention significantly reduced the urine albumin concentration (UAC) at week 12 and 24 endpoints (P < 0.001 at week 12 and 24). The levels of the anthropometric, glucose and lipid parameters (TG and HDL-c), and inflammation biomarkers (CRP and TNF-α) in the EXE group were improved at 12 weeks or 24 weeks, respectively. Meanwhile, a comparison between two groups showed significant changes in anthropometric parameters, glucose parameters, lipid parameters (TG and HDL-c), and Inflammation biomarkers (CRP, IL-6, and TNF-α). Serum fibroblast growth factor 21 (FGF21) was increased in the EXE group (P = 0.005) at week 24, and the change was significantly improved compared with GLAR group (P = 0.003). Correlation network analysis showed that FGF21 had a more central role in improving metabolism in the EXE group, and the change of FGF 21 was significantly negatively correlated with UAC at week 12 and week 24, respectively (r = − 0.297, P = 0.010; r = − 0.294, P = 0.012). Our results showed that EXE could help patients improve UAC, glycemic levels, and inflammatory biomarkers after a follow-up period of 24 weeks intervention. These EXE effects may be partly mediated by FGF 21, indicating that EXE is an effective and safe way to control albuminuria in overweight/obese patients with T2DM.
Highlights
In this study, we investigated the effect of exenatide (EXE), a glucagon-like peptide (GLP)-1 receptor agonist, on kidney function, obesity indices, and glucose control in overweight/obese patients with type 2 diabetes mellitus (T2DM)
There were no significant differences between the two groups in age, gender, duration of diabetes, prestudy antidiabetic treatment, the use of lipid-regulating drugs, and albuminuria before intervention (Table 1)
The results showed that the patients in the EXE group presented more significant improvements in weight and glucose parameters (FBG, HbA1c)
Summary
72 Complete the 24-week follow-up Figure 1. Participants reported the requency (days per week) and duration (time in minutes) of varying levels of physical activity over the previous 7 days. Physical activity is expressed in metabolic equivalent minutes per week (MET-min/wk). The total amount of physical activity performed in a week was determined by calculating the sum of moderate, vigorous, and walking MET-min/wk. In UAC between the two treatment groups, assuming that the data is analyzed on a log-scale, with 0.05 alpha level and an intrasubject coefficient of variation of 50%. Correlation-based network analysis was performed among metabolic parameters adjusted for age and gender were calculated with Pearson’s correlations coefficient on residuals from regression models, including the adjustment variables for each pair of biomarkers. Threshold tests for correlation coefficients (r) and q-values were applied to detect significant correlations. Variables are expressed as frequencies with percentages, median (IQRs), and means (SD)
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