A real-world study of GLP-1 receptor agonists (GLP-1RAs) for treating paಞtients with diabetic kidney disease (DKD) was recently published in the international jo▨urnal Diabetes, Metabolic Syndrome and Obesity.

This retrospective, single-arm real-world study included a total of 364 patients with mild-to-moderate DKD who had been treated with GLP-1RAs for at least 6 months. A hundred and fifty-nine cases were administered PEG-Loxenatide (trade name: Fulaimei), 104 cases Dulaglutide, 52 cases Semaglutide, and 49 cases Liraglutide. The primary endpoint was hemoglobin A1c (HbA1c) levels after 6 months treatment[1]. The results of the study showed that six months of treatment with GLP-1RAs resulted in a significant decrease of 1.77% in the mean HbA1c level, a decrease of 40.3% in the urinary albumin-to-creatinine ratio (UACR), and substantial improvements in 24-hour urinary protein and estimated glomerular filtration rate (eGFR) (all p<0.001). In addition, significant improvements were discovered in patients regarding fasting blood glucose, body weight, blood pressure, and lipid profile (all p<0.001). Notably, patients treated with PEG-Loxenatide accounted for the largest number in this study, but incidences of gastrointestinal adverse events (17.6% vs 30.6% to 51%) and hypoglycemia (3.1% vs 8.2% to 11.5%) were lower compared with those treated with other GLP-1RAs. The study also found GLP-1RAs reduced proteinuria independently of ACEIs/ARBs, and earlier application of GLP-1RA resulted in earlier benefits[1]. DKD is one of the major complications of diabetes[2]. About 30-40% of diabetic patients suffer from DKD[3], which is the main cause of end-stage renal disease (ESRD)[4]. Previously, a randomized controlled trial demonstrated that the efficacy of PEG-Loxenatide in patients with mild-to-moderate DKD was comparable to that of the first-line SGLT2 inhibitors, such as Dapagliflozin, with an additional benefit of improved lipid levels[5]. This real-world study reaffirms that PEG-Loxenatide has demonstrated multiple benefits, including blood glucose reduction, antihypertension, weight loss, lipid improvement, and delayed renal disease progression in mild-to-moderate DKD patients, and also displayed a more favorable safety profile compared with other GLP-1RAs, all of which help to improve patients' quality of life and compliance. PEG-Loxenatide provides more benefits to patients and achieves a superior safety profile, offering a better therapeutic option to DKD patients in the future. 

Abstract

 

Background:

Cardiovascular outcome trials indicate renal benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs); however, real-world efficacy and safety studies in Diabetic kidney disease (DKD) are scarce. 

Methods:

This retrospective, single-arm real-world trial involved adults with DKD treated with GLP-1RA for at least 6 months. The primary endpoint was hemoglobin A1c (HbA1c) levels after 6 months. 

Results:

This study included a total of 364 patients with DKD, 153 (42.0%) of whom were female. The median disease duration was 8.0 years, and the mean values of age, HbA1c level, body mass index, and the urinary albumin-to-creatinine ratio (UACR) were 52.1 years, 8.6%, 27.8 kg/m2, and 88.0 mg/g, respectively. Additionally, 73.6% and 26.4% of patients had mild and moderate DKD, respectively. Following 6 months of GLP-1RA treatment, the mean HbA1c level and UACR declined by 1.77% and 40.3%, respectively (both p < 0.001). Compared to their baseline values, patients exhibited significant improvements in 24-h urinary protein, estimated glomerular filtration rate (eGFR), fasting blood glucose, body weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (all p < 0.001). Patients with a disease duration of <10 years had more pronounced changes in the HbA1c level, UACR, and eGFR (all p < 0.001) than those with a disease duration of ≥10 years. Changes in SBP and DBP were more pronounced in patients also taking angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEis/ARBs) than in those not taking ACEis/ARBs, whereas the changes in UACR and eGFR did not significantly differ. 

Conclusion:

Six-month GLP-1RA treatment improves glucose, blood pressure, lipids, and body weight in patients with mild-to-moderate DKD while slowing down kidney disease progression. It independently reduces proteinuria beyond ACEi/ARB impact, with early use yielding faster outcomes, supporting evidence-based practice. 

Keywords:

diabetic kidney disease, type 2 diabetes, GLP-1RA, HbA1C, UACR