Intensive Glucose Control in Elderly AdultsIntensive Glucose Control in Elderly Adults

To the Editor: In his Clinical Crossroads article, Dr Abrahamson¹ reviewed medications for intensifying glucose control. We were dismayed by his recommendation for intensive glycemic therapy for a 74-year-old woman with no known microvascular disease. Abrahamson implied that the UK Prospective Diabetes Study (UKPDS) clinical trial provided evidence that intensive glycemic control produces cardiovascular benefit in type 2 diabetes; this is not the case. Reviewers of the epidemiological evidence have concluded that for type 2 diabetes (1) there is no experimental evidence suggesting that improved glycemic control produces cardiovascular benefit (the UKPDS clinical trial found no discernable improvements in diabetes-related mortality, cardiovascular events, vision, renal function, pain, symptomatic peripheral neuropathy, amputations, or quality of life over a 10-year period); (2) the UKPDS found significantly lower diabetes-related mortality, stroke, and visual decline from adding 3 to 4 blood pressure medications in pursuit of tight blood pressure control; and (3) in patients who were overweight (>120% of ideal body weight), treatment with metformin monotherapy was associated with reduced diabetes-related mortality and microvascular outcomes, while monotherapy with insulin or sulfonylureas was not, despite similar levels of glycemic control.^{2 - 4} Additionally, and of particular concern for those considering intensifying therapy, combination oral therapy (metformin plus sulfonylurea) was associated with higher diabetes-related mortality.²

Abrahamson may have mistaken cohort (observational) analyses conducted using UKPDS data for true clinical trial results.^{2 ,5} Unfortunately, such cohort analyses do not even represent good observational analyses unless methods are used that adequately account for biases due to differential adherence and selection (eg, healthy volunteer effects).⁵ Journal editors could help prevent such confusion by more rigorously enforcing appropriate labeling of observational studies that use clinical trial databases.⁵

In addition, contrary to Abrahamson's assertion, rigorous examinations of the association between glycated hemoglobin (HbA_1c) values and microvascular disease progression suggest that patients older than 65 years without microvascular complications at baseline will receive little or no appreciable decrease in end-stage microvascular complications from tight glycemic control.^{3 - 4} Therefore, pursuit of tight glycemic control in older patients using intrusive and costly polypharmacy and complex insulin regimens is likely to incur harms and costs that far outweigh the benefit.

For now, whether intensive glycemic control improves cardiovascular outcomes for those with type 2 diabetes is an important but unanswered question. Fortunately, there are 2 large clinical trials in progress designed to answer this question. Until then, intensive, expensive, and intrusive glycemic interventions for elderly persons, like those proposed by Abrahamson, are speculative and potentially dangerous.