Semaglutide: a fourth pillar in diabetic kidney disease

An expert panel published in The Medical Republic this week is outlining how GPs can navigate prescribing and funding barriers for patients with type 2 diabetes and chronic kidney disease — and the shorthand they are reaching for is “four pillars.”

If you or someone you care for has type 2 diabetes and kidney disease, this framework matters. For years, protecting the kidneys in diabetes meant two core strategies: blocking the renin-angiotensin-aldosterone system with an ACE inhibitor or ARB, and controlling blood glucose. That picture has changed substantially in the last five years, and the clinical community is still catching up with how to use all the available tools together.

The four-pillar framework

The structure that is now entering clinical discussion places four drug classes alongside each other — not in competition, but in combination:

First pillar: RAAS inhibitors. ACE inhibitors and ARBs have been the cornerstone of diabetic kidney protection for decades. They reduce proteinuria and slow the rate of kidney function decline. These remain first-line and non-negotiable unless a person cannot tolerate them.

Second pillar: SGLT2 inhibitors. Empagliflozin and dapagliflozin established themselves through the EMPA-REG OUTCOME, CREDENCE and DAPA-CKD trials as agents that reduce kidney disease progression independently of their glucose-lowering effect. They work partly through haemodynamic mechanisms — reducing intraglomerular pressure — that are distinct from RAAS inhibition. Most Australian guidelines now position an SGLT2 inhibitor early in the treatment of type 2 diabetes when eGFR allows.

Third pillar: finerenone. A non-steroidal mineralocorticoid receptor antagonist, finerenone differs from older agents like spironolactone in its selectivity and lower hyperkalaemia risk. The FIDELIO-DKD and FIGARO-DKD trials demonstrated reductions in kidney and cardiovascular outcomes on top of existing RAAS blockade. It is not yet widely prescribed in Australian general practice, in part because familiarity is still developing.

Fourth pillar: semaglutide. The FLOW trial — published in the New England Journal of Medicine in 2024 — enrolled 3,533 people with type 2 diabetes and chronic kidney disease across multiple countries. Participants were randomised to semaglutide 1 mg subcutaneously weekly or placebo and followed for a median of around three years. The trial was stopped early because the results favoured semaglutide: approximately a 24% relative reduction in the primary composite of major adverse kidney events, including sustained 50% or greater decline in eGFR, kidney failure, or death from cardiovascular or kidney causes. A reduction in major adverse cardiovascular events was also observed.

What the trial added to the evidence base was the demonstration that GLP-1 receptor agonists appear to act on kidney biology through pathways that are complementary to the other three pillars — not duplicative of them.

Both-and: the case and the complexity

The evidence case is straightforward. Four drug classes. Four distinct mechanisms. Additive rather than overlapping protection. The conversation in clinical circles is not whether semaglutide works in diabetic kidney disease — the FLOW trial data are robust — but how to implement it practically.

The first complexity is PBS access. Semaglutide is listed on the Pharmaceutical Benefits Scheme for type 2 diabetes management, with criteria linked to HbA1c thresholds and prior agent use. The FLOW trial enrolled participants with eGFR between 25 and 75 — a range that includes many people with meaningful kidney disease — but the PBS listing does not currently reflect the kidney endpoint. A patient whose HbA1c is well-controlled on existing therapy but whose kidney disease is progressing may not meet the criteria under which their GP can prescribe semaglutide on the PBS. That gap between evidence and access is a recurring feature of how Australian public funding of medicines catches up with landmark trial results.

The second complexity is clinical judgement. Not everyone with type 2 diabetes and chronic kidney disease will benefit from all four pillars simultaneously. Tolerability, eGFR trajectories, hyperkalaemia risk, gastrointestinal side effects from semaglutide, and the logistical reality of managing multiple specialist medications through a GP — these are real considerations. The expert panel being published by The Medical Republic is, in part, an attempt to give GPs a practical decision framework rather than just a list of drugs supported by evidence.

The third complexity is the person in the chair. Many patients with type 2 diabetes and CKD are already on multiple medications. Being told there is a fourth drug that may slow their kidney decline — but that costs significantly more out-of-pocket if PBS criteria are not met, or that requires another injection on top of an existing regimen — is not a simple conversation. The system that produced this evidence has not simultaneously produced a straightforward pathway to accessing it.

2 cents

This is not a story about a new drug. Semaglutide has been available in Australia for several years. This is a story about a framework that is now asking GPs to think about diabetic kidney protection differently — to see four complementary tools where they previously saw one or two.

For anyone managing type 2 diabetes with early or established kidney disease: ask your GP to review where you sit against all four pillars, not just the older ones. The question is not “am I on semaglutide?” but “have the drugs I am on been reviewed with the current evidence in mind?” If PBS access is a barrier, that is worth naming explicitly in the consultation so your GP knows to document the clinical reasoning for a streamlined authority application.

For GPs: the Medical Republic panel guidance is worth reading for the practical prescribing decision tree. It is one of the first Australian-specific attempts to translate the four-pillar framing into a usable clinical workflow.

Verdict: yes — the four-pillar approach is well-supported by trial data and clinically relevant now.

---

Sources cited

1. Semaglutide adds a fourth pillar to diabetic kidney care — The Medical Republic, 2 November 2026
2. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes (FLOW trial) — New England Journal of Medicine 2024
3. Chronic kidney disease — Kidney Health Australia
4. NPS MedicineWise — prescribing guidance