Which Antidiabetic Drug Class is Most Renoprotective?

Diabetic kidney disease continues to be a leading etiology of kidney failure. For most of the 20th century, we nephrologists have rightfully focused on the kidney itself while relinquishing diabetes management to our endocrinology colleagues. In recent years, however, a flurry of randomized controlled trials has shown that newer diabetes drugs can both manage blood glucose levels and mitigate deleterious kidney effects.

SGLT2i vs GLP-1a vs DPP-4i

CREDENCE and DAPA-CKD, two of the most highly discussed such trials, focused on the renoprotective effects of sodium-glucose transporter 2 inhibitors (SGLT2i). Other studies, such as LEADER, AWARD-7, and CARMELINA , suggest that glucagon-like peptide 1 agonists (GLP-1a) and dipeptidyl peptidase 4 inhibitors (DPP-4i) also protect the kidneys.

These drugs open a new front in the battle against diabetic kidney disease, but which medication class is the best? Researchers from the St Louis Veterans Affairs Medical Center in Missouri have tried to answer this question.

In the absence of a head-to-head comparisons, they followed a framework proposed by epidemiologists to emulate a 3-year randomized controlled trial of nearly 217,000 US veterans with type 2 diabetes. Patients with suboptimally controlled diabetes and early kidney disease were divided among four treatment arms: SGLT2i, GLP-1a, DPP-4i, and sulfonylureas. Risk for the composite outcome of a decline > 50% in the estimated glomerular filtration rate, development of end-stage kidney disease, or all-cause mortality was measured for each arm over the study period.

Figure 1. Download PDF here

All three of the newer drug classes performed better than the sulfonylureas. Both SGLT2i and GLP-1a offered greater renoprotection than DPP-4i, but neither was notably better than the other, according to the analysis. These findings held for patients at various levels of early and advanced chronic kidney disease and were independent of whether the patients were taking metformin. Data regarding these differences based on insulin or renin-angiotensin-aldosterone system (RAAS) inhibitor use were not included.

Diabetic Kidney Disease Prevention

This randomized controlled trial emulation offers great insights into how we should consider antidiabetic medication classes. SGLT2i and GLP-1a provide a similar and significant renoprotective effect in patients with early chronic kidney disease and suboptimal diabetes control. The foundation for this investigation remains an observational study design. Thus the results should be interpreted with cautious optimism.

Nevertheless, this study highlights antidiabetic agents that we may want to include in our armamentarium along with RAAS inhibitors and selective mineralocorticoid receptor antagonists.

Trial data increasingly suggest that nephrologists should become familiar with newer antidiabetic medication classes and perhaps consolidate their use under the umbrella of a single specialty to stave off diabetic kidney disease. What has been your experience with antidiabetic drug classes and renoprotection? Share your thoughts in the comments below.

Tejas P. Desai, MD, is a practicing nephrologist in Charlotte, North Carolina. His academic interests include the use of social media for physician, student, and patient education. He is the founder of NOD Analytics, a free social media analytics group that serves the medical education community. He has two wonderful children and enjoys spending time with them and his wife.

Follow Tejas P. Desai, MD, on Twitter: @nephondemand

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