Pages

Tuesday, May 29, 2012

Tight Glucose Control No Help to Kidneys

medpagetoday.com Link


Intensive glucose control for type 2 diabetes may help control some markers of kidney health, but doesn't clearly prevent clinical kidney problems, a meta-analysis determined.
Tighter control in clinical trials with hemoglobin A1c (HbA1c) targets ranging from 7.1% to less than 6% significantly cut down on micro- and macroalbuminuria compared with conventional glucose control, Steven G. Coca, DO, MS, of Yale and the VA Medical Center in West Haven, Conn., and colleagues found.
However, the intensive strategy had no impact on doubling of serum creatinine level, risk of end-stage renal disease, or death from renal disease, they reported in the May 28 issue of the Archives of Internal Medicine.
Given the risks of severe hypoglycemia, minimal cardiovascular benefit, and potential increased risk of death seen with tight glucose control, the renal findings don't do much to justify it, Coca's group argued.
Because of the low rates of end-stage renal disease with conventional treatment, "there is little compelling reason to initiate intensive glycemic control in midstage of the disease with the aim of preventing renal failure," they wrote.
However, that message drew criticism in an accompanying editorial by David M. Nathan, MD, of Massachusetts General Hospital in Boston, who argued that it ignores the benefit of intensive intervention early in the course of diabetes.
He pointed to more than 20-year follow-up results from the UKPDS in type 2 and DCCT study in type 1 diabetes showing a reduction in more advanced clinical outcomes, including cardiovascular events.
That is proof that "early intensive therapy, combined with assiduous attention to control of other recognized risk factors, is necessary to improve long-term prospects of patients with diabetes," he wrote.
The meta-analysis largely included studies with follow up "far too brief to address the effects of intensive therapy on end-stage renal disease," he explained.
When combined with the low absolute rates of severe renal outcomes, it couldn't have hoped to do anything but rule out harm, Nathan argued.
"We should be cautious not to abandon the goal HbA1c level of less than 7% for most patients," he concluded.
The guidelines recommend a target of less than 7% but also allow for personalizing treatment goals to anywhere from less than 8% to less than 6.5% based on factors such as age, comorbidity, complications, and hypoglycemia risk.
But there's little trial evidence supporting a goal less than 7%, argued a second editorial.
The UKPDS tested treatment with metformin, a sulfonylurea, or insulin soon after diagnosis but not any specific glycemic target, wrote Karen L. Margolis, MD, MPH, and Patrick J. O'Connor, MD, MPH, both of HealthPartners Research Foundation in Minneapolis, Minn.
"It is clear that using these drugs has benefit and that they may often lower HbA1c to well below 7%, but the UKPDS did not demonstrate the benefit of sustained multidrug therapy to maintain HbA1c less than 7%," they wrote.
ACCORD and ADVANCE were the first trials to achieve and maintain HbA1c less than 7%. Both showed some reductions in early manifestations of microvascular complications with intensive treatment needed for tight glucose control, but neither reduced more advanced microvascular complications or showed benefits for cardiovascular or mortality outcomes.
Those studies were included, along with the two UKPDS cohorts and three other randomized trials, in the current meta-analysis, for a total of 28,065 adults followed over 2 to 15 years.
Compared with conventional glucose control, intensive glucose control was associated with:
  • 14% reduced risk of microalbuminuria (RR, 0.86, 95% CI 0.76 to 0.96)
  • 24% reduced risk of macroalbuminuria (RR 0.74, 95% CI 0.65 to 0.85)
  • No difference in risk of serum creatinine doubling (RR 1.06, 95% CI 0.92 to 1.22)
  • No significant impact on end-stage renal disease (RR 0.69, 95% CI 0.46 to 1.05)
  • No impact on risk of death from renal disease (RR 0.99, 95% CI 0.55 to 1.79)
The greater the difference in HbA1c among the intensive and conventional therapy arms in any particular study, the greater the benefit in terms of microalbuminuria and macroalbuminuria (P=0.01 and P=0.008, respectively).
But the actual median HbA1c in the intensive group didn't correlate with the magnitude of the relative risk for any of the endpoints.
The average diabetes duration prior to study enrollment ranged from 6.5 to 12 years, but that appeared to be a factor only in risk of serum creatinine doubling.
The researchers cautioned about the low cumulative incidence of the clinically important endpoints across the trials (4% doubling of the serum creatinine level, 1.5% end-stage renal disease, and 0.5% death from renal disease), which may have left the meta-analysis underpowered to detect significant differences.
"Regardless, with a baseline rate of end-stage renal disease so low in the standard therapy group and the overall lack of benefit for cardiovascular or all-cause mortality, it does not seem prudent to expose patients to this therapy to achieve an absolute risk reduction for end-stage renal disease that will be less than 1% in a best-case scenario," Coca's group concluded.
Krumholz reported a grant from the National Heart, Lung, and Blood Institute and receiving a research grant from Medtronic through Yale University.
He also reported chairing a scientific advisory board for United Healthcare.
Margolis, O'Connor, and Nathan reported no conflicts of interest.
Primary source: Archives of Internal Medicine
Source reference:
Coca SG, et al "Role of intensive glucose control in development of renal end points in type 2 diabetes mellitus: systematic review and meta-analysis" Arch Intern Med 2012; 172: 761-769.
Additional source: Archives of Internal Medicine
Source reference:
Nathan DM "Understanding the long-term benefits and dangers of intensive therapy of diabetes" Arch Intern Med 2012; 172: 769-770.
Additional source: Archives of Internal Medicine
Source reference:
Margolis KL, O'Connor PJ "Prioritizing treatments in type 2 diabetes mellitus" Arch Intern Med 2012; 172: 770-772.

No comments:

Post a Comment