New T2D Agents Help Prevent, Treat Associated Kidney Disease

By Brenda L. Mooney, /alert Contributor
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Chronic kidney disease (CKD) is a significant risk for patients with type 2 diabetes (T2DM).

A recent review in Expert Opinion on Pharmacotherapy looked at the add-on value of new glucose-lowering agents compared or combined with inhibitors of the renin angiotensin aldosterone system (RAAS) on renal outcomes in T2DM patients.

Belgian researchers summarize the results reported with RAAS inhibitors, the gold standard of nephroprotection in T2DM with albuminuria. The study team from the University of Liège also  describes positive results with both glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter type 2 inhibitors (SGLT2is), pointing out that the latter appeared to be much more effective.

Elderly woman with swollen foot. Source: Getty

In additional to looking at the  potential of combined therapies, the research suggests some new approaches currently in development.

Essentially, study authors report that RAAS inhibitors exert renoprotective effects beyond their blood pressure lowering effects, while SGLT2is, and possibly GLP-1RAs, exert nephroprotection independently of their glucose-lowering activity.

“These effects were demonstrated not only on surrogate endpoints such as albuminuria and estimated glomerular filtration rate decline, but also on hard endpoints, including progression to end-stage renal disease requiring replacement therapy,” they wrote.

The researchers noted, however, that underlying mechanisms are different and potentially complementary on glomerular hemodynamics, arguing for combined therapies.

The authors also called for development of new therapies, adding “there is still room for new emerging drugs to tackle CKD in T2DM.”

The issue is a serious matter, according to an earlier study in the Journal of the American Society of Nephrology, which calculated that kidney disease predominantly accounts for the increased mortality observed in type 2 diabetes.

To reach that conclusion, University of Washington-led researchers examined 10-year cumulative mortality by diabetes and kidney disease status for 15,046 participants in the Third National Health and Nutrition Examination Survey (NHANES III). To do that, they linked baseline data from NHANES III with the National Death Index.

Researchers determined that kidney disease, defined as urinary albumin/creatinine ratio ≥30 mg/g and/or estimated GFR ≤60 ml/min per 1.73 m2, existed in 9.4% and 42.3% of individuals without and with type 2 diabetes, respectively.

Results indicated that, among the reference group -- people without diabetes or kidney disease -- 10-year cumulative all-cause mortality was 7.7% (95% confidence interval [95% CI], 7.0%–8.3%), standardized to population age, sex, and race. At the same time, among patients with diabetes but without kidney disease, standardized mortality was 11.5% (95% CI, 7.9%–15.2%), representing an absolute risk difference with the reference group of 3.9% (95% CI, 0.1%–7.7%), adjusted for demographics, and 3.4% (95% CI, −0.3% to 7.0%) when further adjusted for smoking, BP, and cholesterol.

Among patients with both diabetes and kidney disease, however, standardized mortality was 31.1% (95% CI, 24.7%–37.5%), representing an absolute risk difference with the reference group of 23.4% (95% CI, 17.0%–29.9%), adjusted for demographics, and 23.4% (95% CI, 17.2%–29.6%) when further adjusted. The researchers observed similar patterns for cardiovascular and noncardiovascular mortality.