3 Key Takeaways
Plain English Summary- 01Core Finding
In this descriptive assessment, systematically collected safety data were reported numerically by baseline eGFR.
- 02Study Evidence
Tested in a randomized controlled trial (3533 participants) at the randomized clinical trial stage.
- 03Practical Meaning
Controlled trial findings show causal benefit under protocol rules; real-world effectiveness can vary across patients.
What This Means for You
In this safety assessment, SAEs were reported less frequently with semaglutide than placebo (inactive comparison treatment), with corresponding patterns observed for treatment discontinuations and AESIs. No unexpected safety concerns were identified across the spectrum of eGFR represented in the FLOW trial.
The Discovery
FLOW (NCT03819153) was a double-blind, randomized, placebo (inactive comparison treatment)-controlled trial testing the efficacy (real-world effectiveness in the trial) of just-under-the-skin (subcutaneous) semaglutide 1.0 mg once-weekly on a primary kidney outcome (a clinically meaningful level or more eGFR reduction, kidney failure, or death due to kidney or cardiovascular causes) in participants with T2D and CKD. Safety data were collected selectively and included serious adverse events (SAEs), AEs leading to treatment discontinuation, and prespecified AEs of special interest (AESIs). In this descriptive assessment, systematically collected safety data were reported numerically by baseline eGFR. Of 3533 participants, 1767 received semaglutide and 1766 received placebo. Fewer SAEs were reported with semaglutide than placebo across baseline eGFR subgroups (45.1% versus a clinically meaningful level in the 60 or more ml/min per 1.73 m 2 subgroup, and 56.4% versus 60.4% in the under 30 ml/min per 1.73 m 2 subgroup). SAEs related to infections and infestations; cardiac disorders; respiratory, thoracic and mediastinal disorders; and metabolism and nutrition disorders were generally less frequent with semaglutide than placebo, regardless of baseline eGFR. Treatment discontinuations due to AEs were higher with lower baseline eGFR across treatment groups (60 or more ml/min per 1.73 m 2 : semaglutide 11.2%, placebo 11.3%; under30 ml/min per 66 1.73 m 2 : semaglutide 18.8%, placebo 18.7%). Discontinuations specifically due to gastrointestinal AEs were reported more frequently with semaglutide (4.5%) than placebo (1.1%), regardless of baseline eGFR. Frequencies of AESI were similar between treatment groups across baseline eGFR subgroups.
How It Works, Simply
This nephrology research focuses on glomerular filtration & renal tubular preservation. Researchers evaluated it using a randomized controlled trial (3533 participants) at the randomized clinical trial stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
In this descriptive assessment, systematically collected safety data were reported numerically by baseline eGFR.
- 02Study Evidence
Tested in a randomized controlled trial (3533 participants) at the randomized clinical trial stage.
- 03Practical Meaning
Controlled trial findings show causal benefit under protocol rules; real-world effectiveness can vary across patients.
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Randomized controlled trial
Randomized controlled trial (3533 participants) · Randomized Clinical Trial
Biological Pathway & Modality
Glomerular filtration & renal tubular preservation
Intervention: Safety outcomes of semaglutide by chronic kidney disease severity in the FLOW trial
Experimental Findings & Endpoints
FLOW (NCT03819153) was a double-blind, randomized, placebo-controlled trial testing the efficacy of subcutaneous semaglutide 1.0 mg once-weekly on a primary kidney outcome (a clinically meaningful level or more eGFR reduction, kidney failure, or death due to kidney or cardiovascular causes) in participants with T2D and CKD.
Safety data were collected selectively and included serious adverse events (SAEs), AEs leading to treatment discontinuation, and prespecified AEs of special interest (AESIs). In this descriptive assessment, systematically collected safety data were reported numerically by baseline eGFR.
Of 3533 participants, 1767 received semaglutide and 1766 received placebo. Fewer SAEs were reported with semaglutide than placebo across baseline eGFR subgroups (45.1% versus a clinically meaningful level in the 60 or more ml/min per 1.73 m 2 subgroup, and 56.4% versus 60.4% in the under 30 ml/min per 1.73 m 2 subgroup).
SAEs related to infections and infestations; cardiac disorders; respiratory, thoracic and mediastinal disorders; and metabolism and nutrition disorders were generally less frequent with semaglutide than placebo, regardless of baseline eGFR. Treatment discontinuations due to AEs were higher with lower baseline eGFR across treatment groups (60 or more ml/min per 1.73 m 2 : semaglutide 11.2%, placebo 11.3%; under30 ml/min per 66 1.73 m 2 : semaglutide 18.8%, placebo 18.7%).
Discontinuations specifically due to gastrointestinal AEs were reported more frequently with semaglutide (4.5%) than placebo (1.1%), regardless of baseline eGFR. Frequencies of AESI were similar between treatment groups across baseline eGFR subgroups.
Clinical Translation & Practice Context
In this safety assessment, SAEs were reported less frequently with semaglutide than placebo, with corresponding patterns observed for treatment discontinuations and AESIs.
No unexpected safety concerns were identified across the spectrum of eGFR represented in the FLOW trial.
The Bottom Line · Clinical Pearl
“In this safety assessment, SAEs were reported less frequently with semaglutide than placebo, with corresponding patterns observed for treatment discontinuations and AESIs.”
Published in Kidney International · Current Stage: Randomized Clinical Trial