Glucagon-like peptide-1 receptor agonists and sodium/glucose cotransporter 2 (SGLT2) inhibitors can improve outcomes in patients with type 2 diabetes. Using a nationwide health database in Taiwan, Lee et al applied statistical methods to balance differences between treatment groups and analyze outcomes to examine the comparative effectiveness of these drugs in a real-world setting. AJKDBlog’s Interviews Editor, Timothy Yau (@Maximal_Change), recently sat down with one of the authors of the study, Chia-Hsuin Chang, to discuss the implications of their research.

Dr. Chia-Hsuin Chang is a clinical professor and researcher at National Taiwan University Hospital, specializing in diabetes care. He leverages real-world data to refine treatment strategies and improve outcomes for patients with type 2 diabetes.

 

AJKD Blog: First of all, thank you for highlighting these important drugs that are changing the field of nephrology. There has been so much excitement about SGLT2is over the past decade with CREDENCE, DAPA-CKD, etc.  Similarly, the FLOW trial recently was an encouraging step for the GLP1RA semaglutide. Your trial is the first head-to-head comparison RCT, but what have previous studies shown when looking at the comparative effectiveness of these drugs on kidney outcomes?

Dr Chang: Thank you for your kind words and for taking the time to read our work. We’re grateful for the opportunity to contribute to the growing conversation around these transformative therapies in nephrology.

While previous randomized controlled trials like CREDENCE, DAPA-CKD, and EMPA-KIDNEY have shown strong kidney-protective effects of SGLT2 inhibitors—and more recently, the FLOW trial has demonstrated benefits of the GLP-1RA semaglutide—no trial had directly compared these two classes head-to-head. Prior evidence came from network meta-analyses and observational studies, which have been inconsistent: some suggesting SGLT2is may be more effective, others showing no significant difference. Our study is the first large-scale, real-world comparative effectiveness study using matched cohorts to directly assess these two treatments in patients with type 2 diabetes and chronic kidney disease.

AJKD Blog: Before we dive into your specific study, can you summarize the proposed mechanisms of kidney protection of the two medications you studied, the SGLT2i and GLP1RA drugs?

Dr Chang: Yes. SGLT2 inhibitors reduce glucose and sodium reabsorption in the proximal tubule, leading to natriuresis, restoration of tubuloglomerular feedback, reduction in intraglomerular pressure, and improvement of renal oxygenation and metabolism, which provide early hemodynamic benefits. They also enhance erythropoiesis and reduce inflammation and fibrosis.

GLP-1 receptor agonists, on the other hand, primarily act through metabolic effects—weight reduction, improved glycemic control, and cardiovascular protection. Their kidney protection may also involve anti-inflammatory, anti-oxidative, and antifibrotic effects, but these benefits tend to manifest more gradually. The hemodynamic effects may be not as immediate or pronounced as with SGLT2is.

AJKD Blog: Tell us a little about your population and the research database you used to compare patients who received treatment with these medications. What were the endpoints you looked at?

Dr Chang: We used Taiwan’s National Health Insurance Research Database, which captures over 99% of the population and includes rich clinical data, lab results, prescriptions, and outcome records. We included over 79,000 patients with type 2 diabetes and eGFR < 60 mL/min/1.73 m² from 2016–2021. After propensity score matching, we analyzed 14,182 patients (7,091 in each group).

Our primary endpoint was initiation of kidney replacement therapy (KRT)—including dialysis or kidney transplantation. We also assessed all-cause mortality as a secondary outcome and conducted a composite endpoint analysis using KRT or a 40% decline in eGFR to capture broader progression.

AJKD Blog: You ended up with a very robust cohort of over 14,000 patients. Tell us more about the patients with regards to their kidney function, control of diabetes, and other pertinent characteristics.

Dr Chang: The average age of the cohort was around 67 years, and about 54% were male. The mean eGFR at baseline was 40 mL/min/1.73 m², indicating moderate CKD. Over 70% of patients had ever been on insulin, and the average HbA1c was 9.2%, reflecting relatively poor glycemic control. Notably, patients initiating GLP-1RA had more severe diabetic complications and worse kidney function initially, but these differences were balanced after propensity score matching.

AJKD Blog: Your group followed the cohort for a median of 2.5 years. What did you find in the two groups when it came to your primary outcome? Did anything stand out to you when you analyzed secondary outcomes or subgroup analyses?

Dr Chang: Over the 2.5-year median follow-up, patients initiating GLP-1RA had a significantly higher risk of progressing to KRT compared to those on SGLT2i (HR: 1.39; 95% CI: 1.19–1.63). This difference was especially pronounced among patients with eGFR < 45 or UACR ≥ 300 mg/g. However, when it came to overall mortality, there was no significant difference between the two groups (HR ~0.94). These findings remained consistent in sensitivity and subgroup analyses, emphasizing that SGLT2is may be more effective in slowing CKD progression, particularly in higher-risk patients.

AJKD Blog: One concern that may be brought up is the generalizability of your findings. What would you say about your study’s population of East Asian individuals that may differ from patients in other countries?

Dr Chang: That’s an important point. Our population primarily consisted of East Asian patients with type 2 diabetes, most of whom were non-obese and had advanced CKD with poor glycemic control. While these characteristics may differ from Western cohorts—where obesity and earlier CKD stages are more common—our findings still offer valuable insights, especially for populations with similar clinical profiles. However, further studies in more diverse populations would be essential for broader generalization.

Also, while weekly semaglutide is currently the most commonly prescribed GLP-1 receptor agonist, it was underrepresented in this study. Therefore, the comparative effectiveness of weekly semaglutide versus SGLT2 inhibitors warrants further investigation in future research.

Due to the lack of BMI measurements in the dataset, we could not evaluate whether GLP-1 receptor agonists might be more effective than SGLT2 inhibitors in patients with overweight or obesity—a population that may particularly benefit from the weight-lowering effects of GLP-1RAs.

AJKD Blog: What are the key clinical points that you hope that readers take away from reading your paper?

Dr Chang: The main takeaway is that SGLT2 inhibitors may be more effective than GLP-1 receptor agonists in delaying progression to kidney failure, especially in patients with more advanced CKD or heavy albuminuria. While both drug classes have proven cardiovascular and renal benefits, our findings emphasize the importance of individualizing therapy based on the patient’s kidney risk profile. Healthcare professionals should consider these differences when choosing treatment regimens for patients with type 2 diabetes and chronic kidney disease.

I really appreciate the thoughtful questions and the chance to discuss our study. I hope this conversation helps further awareness and discussion around the evolving role of these therapies in nephrology.

To view Lee et al [subscription required], please visit AJKD.org:
Title: Comparative Effectiveness of Glucagon-Like Peptide-1 Receptor Agonists and Sodium/Glucose Cotransporter 2 Inhibitors in Preventing Chronic Kidney Failure and Mortality in Patients With Type 2 Diabetes and CKD
Authors: Yen-Chieh Lee, Li-Chiu Wu, Vin-Cent Wu, Chia-Hsuin Chang
DOI:  10.1053/j.ajkd.2025.03.016