Ten-Year Follow-up of Intensive Glucose Control in Type 2 Diabetes

Abstract

Conclusion: With 10 years of follow-up, patients with newly diagnosed type 2 diabetes initially treated with intensive glucose reducing therapy have lower long-term risk of myocardial infarction and death from any cause. Summary: The United Kingdom Prospective Diabetes Study (UKPDS) found patients with newly diagnosed type 2 diabetes who received intensive glucose therapy had a lower risk of microvascular complications than patients who received only conventional dietary therapy. This study sought to determine whether improved glucose control persisted in the UKPDS patients and whether such therapy affected macrovascular outcomes in the long term. The original UKPDS study randomized 5102 patients with newly diagnosed type 2 diabetes. Of these, 4209 were randomly assigned to receive dietary restriction (conventional therapy) or intensive therapy using sulfonylurea or insulin, or, in overweight patients, metformin. UKPDS clinics were held for 5 years after the trial ended, and 3277 patients were asked to attend. No attempts were made to maintain previously assigned therapies. Patients unable to attend the clinics were queried with annual questionnaires, and questionnaires were used for all patients in years 6 to 10. Data was analyzed on an intention-to-treat basis with respect to the original randomization categories. Differences in glycated hemoglobin levels among the groups were lost after the first year of completion of the trial. However, the relative reduction in risk persisted at 10 years in the sulfonylurea/insulin group for any diabetes-related end point (9%, P = .04) and microvascular disease (24%, P = .001). Risk reductions were also found for myocardial infarction (15%, P = .01) and death from any cause (13%, P = .007). Patients treated with metformin also had persistent risk reduction for any diabetes-related end point (21%, P = .01), myocardial infarction (33%, P = .005), and death from any cause (27%, P = .002). Comment: This study, with more than 66,000 person-years of follow-up, indicates benefit of intensive blood glucose control in patients with newly diagnosed type 2 diabetes that are followed for 10 years after cessation of randomization intervention. This occurred despite the fact that early trial differences in glycated hemoglobin levels between groups were lost over time; a so-called legacy effect. At first glance this trial would appear to be in direct opposition to the ADVANCE and ACCORD trials, which appeared in the New England Journal of Medicine also in 2008 (N Engl J Med 2008;358:2560-72, and N Engl J Med 2008;358:2545-59). However, the current study, and ADVANCE and ACCORD, studied different groups of patients. The UKPDS group used only newly diagnosed type 2 diabetic patients. The ADVANCE and ACCORD trials involved higher-risk patients aged 8 to 12 years older than those in the UKPDS trial and patients who had been treated for diabetes for 8 to 10 years. A history of macrovascular disease was also present in about 33% of the patients in ADVANCE and ACCORD but in only 7.5% of the patients in the UKPDS. Perhaps the most intriguing result of this study is the sustained legacy effect of early-on intensive glucose control in patients with newly diagnosed type 2 diabetes. Early aggressive treatment appears beneficial, suggesting there may be a move away from the traditional paradigm of initially trying diet alone as therapy for newly diagnosed type 2 diabetes.