Ozempic effective for patients with chronic kidney damage

 A 24-week trial shows up to 52% decrease in urinary protein and 30% reduction in kidney inflammation among participants.

In a recent randomized controlled trial published in Nature Medicine, researchers investigated the effects of semaglutide on albuminuria and kidney disease progression in adults with chronic kidney disease (CKD) and type 2 diabetes (T2D).

They found that treatment with semaglutide significantly reduced albuminuria by 52.1% compared to placebo, with a clinically meaningful impact on kidney disease progression in this population.

Background

Globally, over 2 billion people are living with overweight or obesity, conditions that raise the risk of T2D, CKD, and cardiovascular complications. Obesity-related kidney damage stems from both diabetes and non-diabetes mechanisms, such as inflammation and oxidative stress. While renin-angiotensin system (RAS) and sodium glucose cotransporter 2 (SGLT2) inhibitors reduce CKD progression and cardiovascular risks, residual risks remain, especially with high albuminuria.

Glucagon-like peptide 1 receptor agonists (GLP1-RAs) like semaglutide, known for reducing cardiovascular outcomes, have shown promise in addressing these risks, even among patients with CKD and without diabetes.

Recent findings from the SELECT (short for semaglutide effects on heart disease and stroke in patients with overweight or obesity) trial suggest that semaglutide may slow the decline of kidney function and reduce albuminuria, though more research is needed to confirm its safety and efficacy in non-diabetic CKD patients, especially since a large subset in SELECT was low-risk and not fully treated with RAS inhibitors.

Therefore, researchers conducted a randomized controlled trial to evaluate the effect of once-weekly 2.4 mg subcutaneous semaglutide on lowering albuminuria in patients with CKD and overweight or obesity.

About the study

In the present investigator-initiated, randomized, double-blind, placebo-controlled trial studied the effects of semaglutide on albuminuria in CKD patients without diabetes across 14 centers in the Netherlands, Germany, Spain, and Canada. Inclusion criteria were age ≥18 years, estimated glomerular filtration rate (eGFR) ≥25 ml/min/1.73 m², urine albumin-to-creatinine ratio (UACR) ≥30 and ≤3,500 mg/g, and body mass index (BMI) ≥27 kg/m²).

Participants with a diagnosis of type 1 or 2 diabetes, chronic pancreatitis, uncontrolled thyroid disease, or with a history of recent cardiovascular events were excluded from the trial. The mean age of included participants was 56 years; 40% were women, and 91% were White. They were randomized 1:1 to receive either weekly semaglutide (up to 2.4 mg, n = 51) or placebo (n = 50) for 24 weeks. The study included a screening visit, a run-in phase, treatment, and a washout period.

Primary outcome was the change in UACR at week 24. Secondary outcomes included changes in eGFR, body weight, waist circumference, blood pressure, and high-sensitivity C-reactive protein (hsCRP). Exploratory outcomes were the changes in the level of glycated hemoglobin (HbA1c) and N-terminal pro B-type natriuretic peptide (NT-proBNP). Safety was assessed via adverse event monitoring, with iohexol-based GFR measurements conducted in a subgroup (n = 47). Statistical analysis involved the use of mixed models for repeated measures, log-transformation with back-transformation, and Spearman correlations.

Results and discussion

The most prevalent kidney disease diagnoses among the participants were chronic glomerulonephritis (25%) and hypertensive nephropathy (27%). Additionally, 86% of participants were found to be using angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), while 19% were using SGLT2 inhibitors.

Significant reductions were observed in UACR with semaglutide treatment over 24 weeks, showing a placebo-corrected geometric mean change of -52.1% (P < 0.0001). In contrast, UACR remained stable in the placebo group, with a change of 7.4%. While the semaglutide group experienced an initial decrease in creatinine-eGFR at week 8, the values returned to baseline by week 24, showing no significant difference compared to placebo. Body weight and waist circumference significantly decreased in the semaglutide group by 10.2 kg (P < 0.0001) and 8.8 cm (P = 0.04), respectively.

Additionally, semaglutide treatment was observed to significantly reduce systolic blood pressure by 6.3 mmHg and hsCRP by 37.9%. The change in systolic blood pressure was not found to correlate with the change in UACR in any group. The treatment was generally well tolerated, with gastrointestinal adverse events such as diarrhea and nausea more common in the semaglutide group. There were no significant correlations between changes in body weight and kidney function parameters.

The study is strengthened by the use of iohexol-measured GFR, frequent UACR assessments, and a low drop-out rate. However, the study is limited by the lack of early GFR measurements, limited cystatin C eGFR data, low RAS inhibitor usage, participant homogeneity, and a short follow-up period.

Conclusion

In conclusion, the study shows that 24 weeks of semaglutide treatment significantly reduced albuminuria in patients with CKD and obesity, with an acceptable safety profile. These findings pave the way for further trials to explore semaglutide’s potential in preventing kidney failure and cardiovascular complications in this population.