A quiet breakthrough in diabetic kidney disease
Big-hitting clinical trials with good outcomes are always reserved for the announcement at the annual American Diabetes Association meeting which recently finished. Most are heavily trailed in advance. This year’s spectacular was duly delivered by the LEADER trial (Novo Nordisk), and the results published online in the New England Journal of Medicine (Article). This studied a large number of people with diabetes who were at high cardiovascular risk – for example, people with a previous heart attack. In the trial, those allocated to Victoza for blood glucose (and weight) control had a lower risk of further vascular events (heart attack, stroke and death from a cardiovascular cause) than people treated identically apart from dummy placebo injections. Everyone was taking the best possible medication for blood pressure and cholesterol control, so this effect adds to the benefits of conventional treatment. It isn’t known whether the majority of people with Type 2 diabetes, who are fortunately at lower risk than those studied in LEADER, would gain the same benefit, but we can at least reassure them that there is no increased vascular risk, which was a concern with rosiglitazone, a drug only withdrawn from use a few years ago.
But an equally important study was published at the same time, and although it has been mostly eclipsed by the Victoza news, it is potentially of even greater value because it shows improved kidney outcomes in Type 2 diabetes. Kidney disease, in its late stages requiring dialysis or transplantation, is one of the commonest serious outcomes of Type 2 diabetes, and although it may have passed its peak in the USA, it is still the commonest reason worldwide for someone requiring dialysis. Good blood pressure control, especially with ACE inhibitor drugs or angiotensin receptor blocking drugs, is central, though good glucose control plays some part as well.
A few years ago we were introduced to the ‘flozins’. This is a group of drugs that lower blood glucose levels by encouraging the kidneys to get rid of glucose into the urine. So – they act on the kidneys, but is this good or not-such-good news? In addition to their blood glucose effects, they also reduce blood pressure and also usually cause some weight loss. It looked as though this unlikely group of drugs could be the new good guys of Type 2 diabetes. Their nice image was polished a little more last year when in a large follow-up of high-cardiovascular risk patients (like the LEADER participants) outcomes – heart attacks, strokes, and, uniquely, heart failure – were found to be meaningfully lower in patients treated with one of this group, empagliflozin (Jardiance).
This week the kidney outcomes in these patients were reported, and again it looks like good news. In patients with both normal and slight impaired kidney function at the start of the study 4 years of empagliflozin treatment reduced the risk of developing significant kidney disease – and that included the need for dialysis.
These benefits have only been seen with the specific drugs that were tested, and we await the outcome of similar trials with the other ‘flozins’, canagliflozin (Invokana) and dapagliflozin (Forxiga).
We need caution: for example, another drug like Victoza, Lyxumia, carries no cardiovascular harm, but in a study similar to LEADER, did not show any benefit.
There’s inevitably much excitement, talk of ‘new eras’ and of bright horizons in diabetes treatment, and it’s certainly true that up to 2015 there were no blood glucose lowering drugs that were definitely good for heart disease or kidney disease. No drug is without its downsides. But the Victoza-type group of drugs has been taken by huge numbers of patients for nearly 10 years, and it’s most unlikely we’ll encounter new or unusual side-effects this far down the line. However, the ‘flozins’ are relative newcomers, and drug regulatory agencies are rightly still expecting us to be highly vigilant for known adverse effects and possible emerging ones. But we can be confident that the newer drugs used in Type 2 diabetes are safe in long-term use, and – a muted hurrah for a change – may carry real benefits for meaningful outcomes that affect millions of patients.