Beyond blood sugar control, SGLT2 inhibitors reduce kidney complications: Lancet

Australia: Sodium-glucose co-transporter-2 (SGLT2) inhibitors -- drugs used for lowering blood sugar in people with type 2 diabetes -- also reduce the risk of kidney complications and provides protection against acute kidney injury in diabetic people, according to a recent study.

The study, published in The Lancet Diabetes & Endocrinology journal found that SGLT2 inhibitors reduced the risk of dialysis, transplantation, or death due to kidney disease in individuals with type 2 diabetes. The data provide substantive evidence supporting the use of SGLT2 inhibitors to prevent major kidney outcomes in people with type 2 diabetes.

According to the FDA, SGLT2 inhibitors are a class of prescription medicines that are FDA-approved for use with diet and exercise to lower blood sugar in adults with type 2 diabetes. Medicines in the SGLT2 inhibitor class include canagliflozin, dapagliflozin, and empagliflozin.

They are available as single-ingredient products and also in combination with other diabetes medicines such as metformin. SGLT2 inhibitors lower blood sugar by causing the kidneys to remove sugar from the body through the urine.

Having high blood glucose levels over a number of years is a well-established risk factor for the development of diabetic nephropathy (kidney disease as a result of diabetes). Progression of kidney disease reduces how well the kidneys function and can lead to kidney failure.

Brendon Neuen, The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia, and colleagues performed this systematic review and meta-analysis to assess the effects of SGLT2 inhibitors on major kidney outcomes in patients with type 2 diabetes and to determine the consistency of effect size across trials and different levels of eGFR and albuminuria.

The researchers analyzed data from 4 different studies. More than 38,500 people were included in the analysis. Participants had either been given an SGLT2 inhibitor to take or a placebo.

Among the participants, 943 developed acute kidney injury and 335 went on to develop end-stage renal disease. 252 participants went on to receive kidney dialysis, undergo kidney transplantation or died from kidney disease.

Key findings include:

• SGLT2 inhibitors substantially reduced the risk of dialysis, transplantation, or death due to kidney disease (RR 0·67), an effect consistent across studies.


• SGLT2 inhibitors also reduced end-stage kidney disease (0·65), and acute kidney injury (0·75), with consistent benefits across studies. Although we identified some evidence that the proportional effect of SGLT2 inhibitors might attenuate with declining kidney function, there was clear, separate evidence of benefit for all eGFR subgroups, including for participants with a baseline eGFR 30–45 mL/min per 1·73 m ² (RR 0·70).


• Renoprotection was also consistent across studies irrespective of baseline albuminuria and use of RAS blockade.

"SGLT2 inhibitors reduced the risk of dialysis, transplantation, or death due to kidney disease in individuals with type 2 diabetes and provided protection against acute kidney injury," wrote the authors.

More Information: "SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis" published in The Lancet Diabetes & Endocrinology.

DOI: https://doi.org/10.1016/S2213-8587(19)30256-6

Journal Information: The Lancet Diabetes & Endocrinology