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Tight Glucose Control for Renal Protection Challenged

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Experts Clash on Study's Impact

Most of the trials included in the meta-analysis were too short to draw conclusions about the impact of intensive glucose control on renal disease, according to Dr. David M. Nathan.

"Although implementing intensive therapy is difficult and imposes burden and expense, all of the primary data continue to support its long-term benefit," he asserted.

Dr. Karen L. Margolis and Dr. Patrick J. O’Connor, however, said that the study findings underscore the need for clinicians and patients to weigh the risks and benefits of the treatment regimens needed for intensive glucose control.

"We conclude that for many patients with T2DM, the potential benefits of multidrug intensive glucose control regimens, which are only marginally supported by current evidence, must be weighed against the potential risks of such therapy (including hypoglycemia and possible increased mortality risks) as well as the potentially larger benefits of focusing clinical attention on other domains, such as blood pressure lowering, lipid control, and smoking cessation," they wrote.

Dr. Nathan is director of the General Clinical Research Center and of the Diabetes Center at Massachusetts General Hospital in Boston. His remarks were summarized from an editorial that accompanied the study (Arch. Intern. Med. 2012:172:769-70). Dr. Margolis and Dr. O’Connor are from HealthPartners Research Foundation, Minneapolis, and their remarks were summarized from another editorial (Arch. Intern. Med. 2012:172:770-2). None of the editorialists reported having conflicts of interest.


 

FROM THE ARCHIVES OF INTERNAL MEDICINE

Intensive glucose control had no apparent impact on renal outcomes in type 2 diabetes patients compared to conventional glucose control, according to meta-analysis findings published online in the May 28 Archives of Internal Medicine.

The American Diabetes Association and other expert panels recommend intensive control – defined as a target hemoglobin A1c of less than 7% – to help prevent renal disease and other microvascular complications in type 2 diabetes patients, but the impact of intensive control on clinical renal end points remains unclear, said Dr. Steven G. Coca, of Yale University, New Haven, Conn., and colleagues.

The investigators reviewed data from seven trials involving 28,065 adults with type 2 diabetes. Patient follow-up ranged from 2 to 15 years.

Compared with conventional control, intensive glucose control was associated with a reduced risk of microalbuminuria (risk ratio, 0.86) and macroalbuminuria (RR, 0.74).

However, there was no association with a reduced risk of several renal end points, including no doubling of the serum creatinine level (1.06), end-stage renal disease (0.69), or death from renal disease (0.99).

The mean serum creatinine levels at baseline ranged from 0.9 mg/dL to 1.0 mg/dL, and the mean duration of type 2 diabetes ranged from 7 to 12 years (Arch. Intern. Med. 2012:172:761-69).

An additional meta-regression analysis supported the overall findings. In each study, differences in HbA1c between intensive and conventional control were associated with reduced risk of microalbuminuria and macroalbuminuria, but not with improved renal outcomes.

The results were limited by substantially incomplete outcomes data in several studies, the researchers noted. Many factors may contribute to the failure of tight glycemic control to improve renal outcomes. Possible factors include starting intensive glycemic control too late, failing to maintain intensive control long enough, failing to lower HbA1c levels to normal, and reaching an HbA1c level beyond which there is no additional benefit to the patient. Some of the studies also may have been underpowered to detect a significant difference in renal outcomes.

Despite these limitations, however, the researchers concluded that the current evidence fails to support tight control. "There is little compelling reason to initiate intensive glycemic control in midstage of the disease with the aim of preventing renal failure," they wrote.

Dr. Coca and the editorialists reported having no financial conflicts of interest. Study coauthor Dr. Harlan M. Krumholz is the chair of a scientific advisory board for United Healthcare.

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