In a randomized trial of 41 patients with advanced type 2 diabetic kidney disease, adding empagliflozin to liraglutide increased hemoglobin and reduced body weight but did not improve kidney function, proteinuria, or glycemic control over 6 months.
No eGFR improvementAdding empagliflozin to liraglutide in advanced diabetic kidney disease did not improve kidney function — an important negative finding for clinicians considering combination therapy in late-stage disease
What the researchers found
Adding empagliflozin to liraglutide did not improve eGFR (primary outcome), urinary protein excretion, or glycemic control over 6 months. Empagliflozin significantly increased hemoglobin (12.9→13.7 g/dL, p<0.05) and decreased body weight (66.1→64.5 kg, p<0.05). No significant differences in blood pressure, lipids, or HbA1c.
Why it matters
Both GLP-1 RAs and SGLT2 inhibitors have shown kidney benefits individually. Clinicians increasingly combine these drugs, but evidence for their combined benefit in advanced kidney disease is lacking. This negative result suggests that in advanced-stage disease, the combination may not offer additive kidney protection over GLP-1 RA alone.
The numbers in context
41 patients randomized 1:1. Liraglutide at 1.8 mg/day. Treatment period: 12 months total.
How the study worked
Open-label RCT, 41 patients randomized 1:1. Liraglutide 0.3-0.9 mg/day subcutaneous. Empagliflozin 10 mg daily oral added at 6 months in treatment group. Primary outcome: eGFR change during months 6-12. Secondary outcomes: body weight, blood pressure, hemoglobin, lipids, glucose, HbA1c, urine protein/creatinine ratio.
Who was studied
Patients with advanced type 2 diabetic kidney disease
What this study cannot tell us
Very small sample (41 patients). Open-label design introduces bias. Short 6-month combination period may be insufficient to detect kidney benefit. Japanese population with liraglutide dosing (max 0.9 mg) lower than Western standards (1.8 mg). Advanced kidney disease may have limited reversibility.
How to read the evidence
Rated moderate: randomized controlled trial design, but very small sample (41 patients), open-label, and with Japanese-specific liraglutide dosing that limits generalizability.
When this study was published
Published in 2024. Addresses the clinically relevant question of GLP-1 + SGLT2 combination in advanced kidney disease.
The bigger picture
This is one of the first RCTs examining the combination of GLP-1 RA and SGLT2 inhibitor specifically for kidney outcomes in advanced diabetic nephropathy. The negative result is important — it suggests a ceiling effect or that advanced kidney disease may not respond to combination therapy the way earlier-stage disease does.
Questions still open
- Would higher liraglutide doses (1.8 mg) combined with empagliflozin show different results?
- Is the combination more effective in earlier-stage diabetic kidney disease?
- Does the hemoglobin increase from empagliflozin represent a clinically meaningful benefit in this population?
Common questions
Should GLP-1 and SGLT2 drugs be combined for kidney protection?
Why did empagliflozin increase hemoglobin levels?
Read the original research
Efficacy and Safety of Adding Empagliflozin to Liraglutide on Renal Function in Patients with Advanced-Stage Type 2 Diabetic Kidney Disease: A Randomized Controlled Trial.
Diabetes, metabolic syndrome and obesity : targets and therapy, 17, 3767-3781
Citation
Sunagawa, Kae; Hirai, Keiji; Sunagawa, Sumito; Kamiya, Norifumi; Komesu, Isao; Sunagawa, Yusako; Sunagawa, Hiroshi; Nakachi, Ken; Hirai, Aizan; Ookawara, Susumu; Morishita, Yoshiyuki. (2024). Efficacy and Safety of Adding Empagliflozin to Liraglutide on Renal Function in Patients with Advanced-Stage Type 2 Diabetic Kidney Disease: A Randomized Controlled Trial.. Diabetes, metabolic syndrome and obesity : targets and therapy, 17, 3767-3781. https://doi.org/10.2147/DMSO.S471535