Semaglutide in diabetic kidney disease: safety held even below eGFR 30

Design

Prespecified secondary analysis of a double-blind randomised placebo-controlled trial

Population

3,533 adults with type 2 diabetes and CKD in FLOW

Primary outcome

Serious adverse events, discontinuations and adverse events of special interest by baseline eGFR

Effect

Serious adverse events below eGFR 30: 56.4% vs 60.4%; GI discontinuation 4.5% vs 1.1% overall

FLOW randomised 3,533 people with type 2 diabetes and CKD to weekly subcutaneous semaglutide 1.0 mg or placebo and showed kidney and cardiovascular benefit. This prespecified secondary analysis looked at safety by baseline eGFR, because side effects and intolerance often worsen as kidney function falls.

Serious adverse events were less common with semaglutide than placebo in every eGFR subgroup: 45.1% against 50.4% at eGFR 60 or more, and 56.4% against 60.4% below 30. Serious infections, cardiac, respiratory and metabolic events were generally less frequent on semaglutide. Discontinuation for any adverse event rose as eGFR fell but was the same in both arms (about 11% at eGFR 60 or more, about 19% below 30). Discontinuation for gastrointestinal effects was higher with semaglutide (4.5% vs 1.1%) at every level.

The practical message is that low eGFR is not, in itself, a reason to withhold semaglutide in type 2 diabetes with CKD. Gastrointestinal tolerability, slow titration and nutrition need attention, particularly in frail patients near kidney failure. The analysis is descriptive, without formal comparisons between subgroups.

• Do not withhold semaglutide in type 2 diabetes with CKD because eGFR is low.
• Titrate slowly and review gastrointestinal symptoms, the main reason for stopping.
• Watch appetite, weight and nutrition in frail patients with advanced CKD.
• Continue alongside RAS blockade and SGLT2 inhibitors as part of combined kidney protection.
• Check volume status if vomiting or diarrhoea develop, given the risk of acute kidney injury.

Why it matters

Clinicians often hold back new drugs as eGFR falls; for semaglutide, the safety data do not support that hesitation.

Don't overread it

This is a descriptive subgroup analysis without formal statistical comparison between eGFR groups.

The statistics, in plain English

Fewer serious adverse events on the active drug than on placebo usually reflects the drug preventing illness, such as heart and kidney events, rather than causing none. Descriptive subgroups show consistency but cannot prove equal effect in each.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.