Intensive Glucose Control in Older Patients With Diabetes

An 82-year-old patient was diagnosed with diabetes several years ago based on a fasting blood glucose level of 150 mg/dL (8.32 mmol/L) and confirmed by an A1C of 8%. She was otherwise healthy and physically active and, until then, had used diet and exercise to keep her A1C at approximately 8%. When the A1C increased to 9%, you prescribed low-dose metformin, lowering the A1C to 8.5%. But her son worried and took her to an endocrinologist, who convinced both of them that tighter control was necessary to prevent a stroke, severe kidney disease, or death.

The endocrinologist prescribed an intensive regimen of nighttime insulin glargine, sitagliptin (Januvia), and the maximum metformin dose, decreasing the patient's A1C to the endocrinologist's desired goal of 6%. The endocrinologist prescribed a continuous glucose monitor so the patient could track her blood glucose levels constantly. Soon her gait became unsteady, and she developed dizziness, fatigue, and occasional confusion. The endocrinologist referred her to a neurologist, cardiologist, and nephrologist, and more drugs were prescribed. The patient's son was happy with his mother's improved A1C level, but she was not. She asked you, “Why do I feel so terrible?”

Benefits of Intensive Control of Type 2 Diabetes

In 1998, the American Diabetes Association broadened its definition of diabetes, lowering the cutoff fasting glucose value from 140 mg/dL (7.77 mmol/L) to 126 mg/dL (6.99 mmol/L). This change nearly doubled the number of Americans with diabetes from 2.2 million to 4.1 million and led to more intensive blood glucose targets, even though no randomized data prompted the change and no evidence demonstrated that lower targets would lead to better outcomes.¹ Since then, the introduction of a new diagnosis of prediabetes has broadened calls for more surveillance and intensive treatment, although no evidence shows any prognostic value to labeling people with prediabetes.² In fact, the American Diabetes Association now states that 75% of Americans older than 65 years have prediabetes (50%) or diabetes (25%).³

As a 2013 Cochrane review found, virtually all data demonstrating benefit from intensive glucose control in adults—pushing A1C levels lower than 6.5% —derive from observational studies that may not have adequately controlled for confounding factors. In contrast, the Cochrane review's analysis of several large randomized trials showed that intensive control does not improve macrovascular outcomes at any age, does not increase longevity, and likely does not improve microvascular outcomes other than surrogate markers such as albuminuria.⁴

The ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial—one of the largest randomized trials of adults— was discontinued because the mortality rate increased in the intensive treatment group.⁵ A large Veterans Affairs study⁶ and the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) study⁷ showed no clinical benefit other than a reduction in nonfatal myocardial infarctions, but they did not replicate the ACCORD trial's finding of increased mortality rates. No subsequent randomized studies have shown benefits in patient-oriented outcomes, although the study durations may not be sufficient to do so.^8,9