Diabetes Drug Combo Shields Kidneys Best
GLP-1 Agonists Offer Superior Protection in New Study
A recent analysis reveals that combining metformin with a GLP-1 receptor agonist significantly enhances kidney protection for individuals with type 2 diabetes and related kidney disease (DKD). This combination proves more effective than other metformin-based treatment regimens.
New Insights into DKD Management
A comparative study, published in July 2025, examined various antidiabetic medication combinations for their ability to preserve kidney function in patients aged 18 and older diagnosed with type 2 diabetes and DKD. Crucially, individuals with a glomerular filtration rate (eGFR) above 15 mL/min/1.73 m2 were excluded from the research.
The research team categorized participants based on their metformin adjunct therapy: metformin plus a GLP-1 receptor agonist, metformin with a DPP-4 inhibitor, or metformin with other antidiabetic medications (oADMs). The study’s main goal was to assess a composite endpoint of a 50% decline in eGFR or the onset of end-stage renal disease (ESRD), defined as an eGFR below 15 mL/min/1.73 m2. A secondary outcome included the primary endpoint alongside all-cause mortality. The analysis established a baseline one year before adjunct therapy initiation and tracked patients for three years.
Rigorous Analysis for Unbiased Results
To minimize bias, researchers meticulously stratified patients by age, sex, body mass index (BMI), glycated hemoglobin (HbA1c), and use of ACE inhibitors or ARBs. They employed propensity score matching (PSM) to account for factors like medications and comorbidities that might influence DKD progression, ensuring a more reliable comparison.
Following PSM, baseline characteristics such as age, HbA1c, and eGFR were comparable across groups. Hypertension was present in approximately 76% of patients, with 44% using ACE inhibitors and 16% using ARBs. The majority, about 80%, had DKD stage 1 (eGFR ≥ 90 mL/min/1.73 m2), while 20% had stage 2 (eGFR 60-89 mL/min/1.73 m2).
GLP-1 Agonists Emerge as Kidney Protectors
The study found that the metformin/GLP-1 receptor agonist group experienced a significantly lower risk of kidney impairment compared to the metformin/DPP-4 inhibitor group. Further analysis indicated that older patients (55+), females, those with a BMI of at least 31 kg/m2, or individuals with an HbA1c above 6.5% showed a reduced risk when using metformin plus a GLP-1 receptor agonist.
When compared to the metformin/oADM group, the metformin/GLP-1 receptor agonist cohort demonstrated a substantially lower risk of the secondary outcome, including the composite endpoint and mortality. Specifically, older patients (55+) on this combination appeared to have a diminished risk of kidney impairment.
No significant differences in primary or secondary outcomes were observed between the metformin/DPP-4 inhibitor and metformin/oADM groups. Interestingly, females using metformin and a DPP-4 inhibitor seemed to face a lower risk of kidney impairment.
Clinical Recommendations and Considerations
These findings align with existing research highlighting the kidney-protective benefits of GLP-1 receptor agonists in DKD. While metformin/DPP-4 inhibitor combinations offer cardiovascular advantages alongside glycemic control, they do not appear to provide kidney protection.
Consultant pharmacists should consider GLP-1 receptor agonists as a second-line treatment for older adults with DKD needing enhanced glycemic management. It’s vital to monitor for potential side effects like nausea, vomiting, diarrhea, or constipation, as well as weight loss.
Emergency department pharmacists should be vigilant for volume depletion due to nausea and vomiting in patients on GLP-1 receptor agonists, as this can contribute to acute kidney injury. Nurse practitioners can consider GLP-1 receptor agonists after metformin and SGLT2 inhibitors when additional glycemic control is required. This study provides valuable real-world evidence supporting the guideline-recommended use of these agents for kidney protection in DKD.
The broader impact is significant: according to the CDC, in 2021, over 30 million Americans had diabetes, and a substantial portion also experienced chronic kidney disease (CDC, 2023). This research offers a clearer path to managing DKD effectively.
