ORLANDO — Intensive glycemic control did not reduce the risk for developing advanced measures of microvascular outcomes, although it did delay the onset of albuminuria and some measures of eye complications and neuropathy among patients with longstanding type 2 diabetes at high cardiovascular risk.
The mixed results, from a subanalysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, suggest that the microvascular benefits of intensive therapy should be weighed against the increase in total disease-related mortality, increased weight gain, and high risk for severe hypoglycemia that emerged with the main findings of the trial 2 years ago, said Dr. Faramarz Ismail-Beigi said of Case Western Reserve University, Cleveland. The findings were released simultaneously online in the Lancet (doi:10.1016/S0140-6736(10)60576-4).
The ACCORD trial randomized 10,251 adults with type 2 diabetes to either intensive glycemic control with a target hemoglobin A1c of less than 6.0%, or standard therapy aiming for HbA1c values of 7.0%-7.9%. The intensive arm was stopped early in February 2008—after a median follow-up of 3.7 years—because of a 22% higher all-cause mortality in the intensive group. They were then transitioned to standard therapy for the rest of the trial, which also included blood pressure and lipid control arms (N. Engl. J. Med. 2008;358:2545-59).
At the time of that transition and at study end, the two groups did not differ in the prespecified primary composite outcome of advanced nephropathy and diabetic eye complications (development of renal failure or retinal photocoagulation or vitrectomy to treat retinopathy), nor in a second composite end point that added a peripheral neuropathy outcome (score of greater than 2.0 on the Michigan neuropathy screening instrument or the first composite outcome). At the end of the study, 10.9% of the intensive group and 11.5% of the standard treatment group met the first composite end point, and 38.2% and 40.0%, respectively, met the second.
However, microvascular renal outcomes based on urinary measures were significantly reduced in the intensive glycemic therapy group. Intensive glycemia therapy led to a 21% reduction in the development of microalbuminuria at the time of transition. This effect was attenuated to 15% at study end, but remained statistically significant, Dr. Ismail-Beigi reported.
For diabetes-related eye events, three-line worsening of visual acuity was more common in the standard group than in the intensive group at both transition and study end (20.7% vs. 19.1%). Peripheral neuropathy (MNSI greater than 2.0) was less common in the intensive group than in the standard group at study end (55.6% vs. 58.6%).
The ACCORD trial was funded by the National Heart, Lung, and Blood Institute, with contributions of medications, equipment, or supplies from several manufacturers.
Several coauthors declared financial relationships with many manufacturers of diabetes-related products.
Weigh the risks vs. benefits of intense therapy, said Dr. Faramarz Ismail-Beigi (right).
Source Miriam E. Tucker/Elsevier Global Medical News