Intensive Glucose Control, Long-term Kidney Benefit in Diabetes

Marlene Busko

April 05, 2016

Compared with patients with type 2 diabetes who received standard care, those who received 5 years of intensive glucose-lowering treatment were less likely to develop end-stage renal disease (ESRD) during a total of almost 10 years of follow-up, new research indicates.

The study, by Dr Muh Geot Wong, from the George Institute for Global Health, University of Sydney, Australia, and colleagues, was published online March 23 in Diabetes Care.

The researchers homed in on renal outcomes in 8494 patients who had first been randomized to receive intensive glucose lowering vs standard care in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Released Controlled Evaluation (ADVANCE) study and then completed the follow-up ADVANCE-ON trial.

"This study highlighted that a period of intensive glucose control continues to protect against the development of ESRD in patients with type 2 diabetes," Dr Wong told Medscape Medical News.

Importantly, those with initial preserved kidney function and without systolic hypertension benefited the most.

Thus, "our results highlight the importance of achieving intensive glucose control as early as possible to prevent the development of future serious diabetic kidney disease," Dr Wong emphasized.

Moreover, unlike in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial — where intensive glucose lowering was tied to an increased mortality risk in patients with chronic kidney disease (CKD) — in ADVANCE-ON, a period of tight glucose control did not affect overall all-cause mortality, cardiovascular mortality, major cardiovascular events, MI, or stroke — regardless of baseline kidney function.

Diabetes Now Number One Cause of ESRD

Despite the implementation of "best-practice" standards of care for lifestyle modification and blood-pressure lowering, there remains a high level of progression to ESRD for those with diabetic kidney disease, Dr Wong and colleagues note.

And diabetes has now surpassed glomerulonephritis as the most common cause of ESRD in the developed world and many developing countries.

Hence, there is a renewed interest in the role of intensive glucose control in development of ESRD, they note.

The type 2 diabetes patients in ADVANCE received intensive or standard glucose-lowering interventions for a median of 5.0 years, and those who went on to participate in the ADVANCE-ON posttrial all received standard care and were followed for a further 6 years (median, 5.4 years).

In September 2014, the researchers published overall results from ADVANCE-ON; the current analysis takes a deeper dive into how intensive glucose control in diabetic patients with different initial renal function affected the risk of ESRD (defined as needing dialysis or a kidney transplant), cardiovascular events, and death.

Patients who received intensive glucose lowering in ADVANCE were less likely to develop ESRD than patients who received standard care (seven events vs 20 events; hazard ratio [HR], 0.35; P = .02), and this benefit persisted in the posttrial follow-up, ADVANCE-ON (29 events vs 53 events; HR, 0.54; P < .01).

NNT to Prevent One ESRD Event Is 109 for Those With Early Disease

Expressed differently, the number needed to treat (NNT) with intensive glucose-lowering therapy to prevent one ESRD event during 9.9 years was 194 patients.

The NNT to prevent one ESRD event was lower for patients with baseline stage 1 or 2 CKD, at 109, or systolic blood pressure < 140 mm Hg, at 120, and it was greater for patients with baseline stage 3 or higher CKD or systolic blood pressure > 140 mm Hg (NNT = 393 and 368 patients, respectively).

"Our results highlight the importance of commencing intensive glucose control before diabetic kidney disease develops, as lesser renal benefit was observed in participants with an established reduction in kidney function," Dr Wong and colleagues state.

"Our data build on a growing body of evidence indicating an important role for intensive glucose control in limiting the progression of kidney disease and in curbing the growing number of patients around the world with type 2 diabetes requiring dialysis or transplantation as a result of diabetic kidney disease," they conclude.

The ADVANCE trial and ADVANCE-ON follow-up study were funded by unrestricted grants from Servier and the Australia National Health and Medical Research Council. Dr Wong reports fees for scientific lectures from AstraZeneca. Disclosures for the coauthors are listed in the article.

Diabetes Care. Published online March 23, 2016. Abstract

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