A few weeks ago, we wrote about pharmaceutical company AstraZeneca halting an ongoing trial of its drug Farxiga (generic name dapagliflozin) for the treatment of chronic kidney disease (CKD) due to an “overwhelming” benefit from the drug seen in preliminary results. This was a potentially major development in the treatment of CKD, since there are currently few effective drug treatments available for the disease. Farxiga was developed, and is already approved, as a drug for type 2 diabetes. It works by preventing reabsorption of glucose in the kidneys.
Since diabetes is the leading cause of CKD due to the damaging effect of high blood glucose levels on the small blood vessels in your kidneys, any beneficial side effects on kidney function in people who take a drug for diabetes would be especially welcome. And a new study confirms that Farxiga and other SGLT2 inhibitors — which all work in much the same way, by making your kidneys excrete more glucose in your urine — appear to protect against major kidney problems in people who take them for diabetes.
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Published in the journal BMJ, the new study looked at the use of three different SGLT2 inhibitors — Farxiga, Jardiance (empagliflozin) and Invokana (canagliflozin) — in nearly 30,000 people who started taking the drug for their type 2 diabetes. Researchers compared this group against an equal number of people with diabetes who started taking a drug from a different class, DPP-4 inhibitors, which includes Januvia (sitagliptin), Tradjenta (linagliptin), Nesina (alogliptin) and Onglyza (saxagliptin).
From the start of taking their respective drug, participants were followed for an average of 1.7 years. At the beginning of the study, the average age of participants was 61 years, and 19% of them had cardiovascular disease, while 3% already had CKD.
The main outcome the researchers were interested in was serious renal (kidney) events, defined as a combination of renal replacement therapy (dialysis or hemofiltration), death from kidney-related causes, or admission to a hospital for a kidney-related event. The researchers also looked at each of these outcomes individually.
The researchers found that participants who took SGLT2 inhibitors experienced 2.6 serious renal events per 1,000 people per year, compared with 6.2 in the DPP-4 inhibitor group — an overwhelming difference, indicating that the SGLT2 inhibitor group was only 42% as likely to experience these outcomes. Furthermore, the SGLT2 inhibitor group was 32% as likely to need renal replacement therapy, 41% as likely to be hospitalized for kidney-related events, and 77% as likely to die from kidney-related causes.
After adjusting for differences between the two study groups including those in HbA1c level (a measure of long-term blood glucose control), blood pressure, body-mass index (BMI), and smoking status, the researchers found that members of the SGLT2 inhibitor group were still only 55% as likely to experience serious renal events as those in the DPP-4 inhibitor group.
As noted in a ScienceDaily article on the study, the researchers also found that participants who already had CKD experienced an even greater benefit from taking SGLT2 inhibitors, in terms of serious renal events, than participants who didn’t have CKD. This result suggests that SGLT2 inhibitors may be a good choice of medication for people who have both type 2 diabetes and CKD.
It’s important to note a couple of potential limitations of the new study. First, it took place in Sweden and Denmark, and its results may not translate to all populations with diabetes or CKD. Second, as an observational study, it didn’t randomly assign participants to either of the two groups, which means that certain factors could have influenced both which drug a participant was prescribed and the outcomes of the study. In fact, the change in risk reduction from 42% to 55% once researchers took certain differences between the groups into account shows that these characteristics did, in fact, influence outcomes. It’s unknown whether other factors that the researchers didn’t look at could have also influenced the results.
Still, the large difference in serious renal events between the two groups — even after controlling for factors like HbA1c and BMI — suggests that SGLT2 inhibitors offer kidney protection. Further studies may be useful to examine which SGLT2 drugs offer the greatest benefit in this area.
Want to learn more about keeping your kidneys healthy with diabetes? Read “Managing Diabetic Kidney Disease,” “Kidney Disease: Your Seven-Step Plan for Prevention” and “Ten Things to Know About Kidney Disease.”
