OBJECTIVE: To examine the effects of oral semaglutide on kidney outcomes in people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD).
RESEARCH DESIGN AND METHODS: SOUL (NCT03914326), a double-blind randomized controlled trial, compared oral semaglutide with placebo in people with T2D, ASCVD, and/or CKD, showing a 14% reduction in risk of major adverse cardiovascular (CV) events. Prespecified kidney outcomes included a five-point composite (=50% decrease in estimated glomerular filtration rate [eGFR], persistent eGFR <15 mL/min/1.73 m2, initiation of chronic kidney replacement therapy, or death from kidney or CV causes); a four-point composite (excluding CV death); and eGFR decline. Prespecified subgroups were also assessed, including those with eGFR <60 mL/min/1.73 m2 at baseline.
RESULTS: Among 9,650 participants, mean eGFR was 73.8 mL/min/1.73 m2, and follow-up was 47.5 months. The five-point outcome occurred in 403 (8.4%) and 435 (9.0%) participants taking oral semaglutide versus placebo, respectively (hazard ratio [HR] 0.91; 95% CI 0.80, 1.05; P = 0.19). The four-point outcome occurred in 112 (2.3%) and 129 (2.7%) participants, respectively (HR 0.86; 95% CI 0.66, 1.10; P = 0.22). Mean annual eGFR decline was less with oral semaglutide than placebo (-1.67 vs. -2.06 mL/min/1.73 m2; estimated treatment difference 0.40 [95% CI 0.27, 0.53; P < 0.0001). These effects were similar across most subgroups, including those with eGFR <60 mL/min/1.73 m2. Serious adverse events occurred at similar rates in both groups.
CONCLUSIONS: In people with T2D and ASCVD and/or CKD but with overall mostly preserved eGFR, orally administered semaglutide, compared with placebo, did not significantly reduce adverse kidney outcomes but did slow the decline in eGFR.
| Discipline Area | Score |
|---|---|
| Internal Medicine |  |
| Endocrine | |
| Nephrology | |
| Cardiology |  |
| Family Medicine (FM)/General Practice (GP) | |
| General Internal Medicine-Primary Care(US) | |
Oral semeglutide had modest beneficial effect on renal function.
This study provides high-quality evidence that oral semaglutide slows eGFR decline and is safe in people with T2D and ASCVD and reinforces the reno protective effect of semaglutide.
Very useful research study.
Irrelevant big pharma study of a drug that has no effect on renal outcomes in person with diabetes.
As a primary care physician, this is helpful data; however, we must keep in mind that this is a subgroup analysis. What we see is that the (current) maximum dose of oral semaglutide does not provide the same sort of end-organ benefits as we've come to expect from SC GLP1a's. So we can counsel our patients that based on what we currently know, injectable GLP1a continues to be superior to the oral version.
This is a relevant article because injectable GLP-1 receptor agonists have demonstrated value in reducing the progression of chronic kidney disease as well as in preventing cardiovascular events. This has generated particular interest in oral semaglutide as it is a preferable option for many patients due to the convenience of oral administration compared with injections. Knowing that it does not provide a significant benefit in preventing deterioration of kidney function is a useful clinical tool to help explain to patients why oral semaglutide is not preferable over injectable formulations.
