The reduction of microvascular complications, such as nephropathy, neuropathy, and retinopathy, by achieving intensive glycemic control with the use of insulin, has been well established in patients with T1DM or T2DM.45-48 Nonetheless, the landscape of glycemic control changed with the completion of the Action to Control Cardiovascular Risks in Diabetes (ACCORD) trial, the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, and Veterans Affairs Diabetes Trial (VADT).49,50,51 Based on the findings from those trials, caution is advised against the indiscriminate setting of very low glycemic targets. Findings from subanalyses of data from those trials suggest that while most patients are likely to achieve a microvascular benefit from intensive control, others may potentially be harmed by cardiovascular events. Those likely to benefit are those with short-duration DM, a long life expectancy, and no significant cardiovascular disease. Those who may be harmed and in whom an A1C goal <7.0% may not be appropriate are those with a history of severe hypoglycemia, a limited life expectancy, advanced microvascular or macrovascular complications, extensive comorbidities, or long-standing DM in whom the more stringent A1C goal may be difficult to attain.52
Misconceptions and Limitations Regarding Insulin
Insulin therapy is considered by some clinicians and patients to be the most complicated and time-consuming of the glucose-lowering therapies. Concerns about self-injection, the need for dosage adjustment, and cost, as well as the stigma of insulin as last-line therapy, are common. Additionally, in some studies with follow-up to 24 months, patients’ adherence to insulin therapy has been reported to be 54% to 81% in patients with T2DM.53-55 When used properly, insulin is the most efficacious glucose-lowering therapy and, therefore, may help motivate patients to adhere to insulin therapy. Hypoglycemia and weight gain are also common concerns of patients and clinicians, although insulin analogs are an improvement compared with older insulins. The risk for hypoglycemia requires that patients be educated regarding the signs and symptoms and actions to be taken should a hypoglycemic episode occur. Self-monitoring of blood glucose is required and is of crucial importance in patients using multiple insulin injections or insulin-pump therapy.56 Devices for continuous glucose monitoring may also be used to reduce the incidence of hypoglycemia. Because weight gain associated with insulin therapy may be a demotivating factor in patients, lifestyle management and patient education are essential. Education should include consequences of poor glycemic control and disease progression, and the expected benefits with regard to quality of life. Using a collaborative approach to individualize therapy and to match the type of insulin and insulin dosing with a patient’s lifestyle habits, such as food intake and daily activities, fosters patient self-management and may help to minimize the risks and maximize the benefits of insulin therapy.
Conclusions
Since its discovery nearly a century ago, insulin has evolved to greater purity, with pharmacokinetic and pharmacodynamic profiles that more closely resemble insulin secretion by the pancreas. The insulin analogs are now recommended for treatment of patients with T1DM or T2DM because they are better tolerated and more physiologically similar to endogenous insulin compared with older formulations, including human insulins. Insulin analogs delivered and monitored with current pens and devices provide clinicians with improved ability to better manage patients with DM.
