Effects of early, intensive glycemic control endure for decades, UKPDS data show

Twenty-four years after beginning intensive therapy with a sulfonylurea, insulin, or metformin in the United Kingdom Prospective Diabetes Study (UKPDS), type 2 diabetes patients had significant reductions in mortality compared with patients getting conventional glycemic control.

Early intensive glycemic control with a sulfonylurea or insulin, or with metformin, appears to confer long-term reduced risk of death and myocardial infarction compared with glycemic control methods conventional at the time, according to a 24-year post-trial monitoring study.

Between 1977 and 1991, 4,209 people newly diagnosed with type 2 diabetes were randomized to receive either intensive glycemic control (sulfonylurea or insulin, or if overweight, metformin) or conventional glycemic control (primarily diet) as part of the United Kingdom Prospective Diabetes Study. Researchers previously reported treatment effects during a 10-year post-trial monitoring period. To test whether these effects would wane over time, researchers extended the follow-up by another 14 years, linking 1,489 patients (mean age at baseline, 50.2 years; 41.3% female) to their routinely collected National Health Service data. Findings from the extended follow-up period were published by The Lancet on May 18.

At the end of the follow-up period, in September 2021, mean age was 79.9 years and patients had a median follow-up time of 17.5 years. Compared with conventional glycemic control, early intensive glycemic control with sulfonylurea or insulin therapy was linked with overall relative risk reductions of 10% (95% CI, 2% to 17%; P=0.015) for death from any cause, 17% (95% CI, 6% to 26%; P=0.002) for myocardial infarction, and 26% (95% CI, 14% to 36%; P<0.0001) for microvascular disease, with corresponding absolute risk reductions of 2.7%, 3.3%, and 3.5%, respectively. Metformin therapy showed overall relative risk reductions of 20% (95% CI, 5% to 32%; P=0.010) for death from any cause and 31% (95% CI, 12% to 46%; P=0.003) for myocardial infarction compared with conventional glycemic control, with corresponding absolute risk reductions of 4.9% and 6.2%, respectively. Patients taking metformin did not have a significant reduction in microvascular disease, and neither intensive group had significant reductions in stroke or peripheral vascular disease.

One limitation to the study is that researchers did not have access to participants' HbA1c levels or information about other pharmacotherapy. Overall, "analyses show that the previously identified glycemic and metformin legacy effects do not wane for up to 24 years after the trial ended," the authors wrote. "Achieving near normoglycemia immediately following diagnosis might be essential to minimize the lifetime risk of diabetes-related complications to the greatest extent possible," they added.

The findings may be of particular importance to managing diabetes in low-income settings as all the therapies used in the original study are off patent and have been previously shown to be cost-effective or cost-saving, the authors said.