Volume 113, Issue s42

“Insulin will never be a success in the treatment of diabetics without the aid of the general practitioner.” 1 These words, written by Elliott P. Joslin, MD, in 1923, still ring true today. After the first successful insulin injection was administered on January 23, 1922, to Leonard Thompson, a 14-year-old patient with type 1 diabetes mellitus at Toronto General Hospital, it did not take long before a diabetes clinic using insulin treatment was set up. 2 Insulin was subsequently provided to physicians in the United States for clinical trials, although many US patients with diabetes mellitus presented themselves to Sir Frederick Banting, MD, co-discover of insulin, in Toronto for insulin treatment. Within 2 years, insulin was being manufactured by multiple pharmaceutical companies and was available commercially in both the United States and Canada. 2 Almost immediately, health care professionals and others identified the problem of who was going to care for all of these patients. Patients were arriving at diabetes clinics expecting to receive insulin, often overwhelming the few physicians who were educated on the care of diabetic patients. For this reason, the physicians and nurses at the New England Deaconess Hospital in Boston initiated a teaching program so that general practitioners could learn all aspects of the management of diabetes. 1

Progressive hyperglycemia is a characteristic of type 2 diabetes mellitus (T2DM) that poses a challenge to maintaining optimal glycemic control. Achieving glycemic control early in the course of disease can minimize or prevent serious complications. Most patients with T2DM eventually require insulin replacement therapy to attain and preserve satisfactory glucose control. For decades, the use of insulin to address the primary defect of T2DM has been a cornerstone of diabetes therapy. Insulin is indicated for patients with T2DM presenting with clinically significant hyperglycemia, and it is mandatory for patients exhibiting signs of catabolism. Insulin should be considered for patients in whom hyperglycemia persists despite attempts to control the condition through diet and exercise modifications and the use of noninsulin therapies. Many physicians delay initiation of insulin until absolutely necessary, sometimes overestimating patient concerns about its use. Modern insulin analogs, treatment regimens, and delivery devices make insulin more user friendly, and physicians can promote patient acceptance of insulin by reviewing the benefits of controlled glycated hemoglobin levels and addressing patient concerns.

Initiating and advancing insulin therapy in patients with type 2 diabetes mellitus can be challenging. However, with the availability of insulin analogs with more physiologic profiles, and with the initiation of simple insulin regimens (eg, the use of basal insulin administered once daily), an opportunity is created to empower patients to self-titrate their insulin. Self-titration can reduce the burden on the physician as well as improve glycemic control in patients. More options for intensifying insulin now exist, including gradually adding prandial insulin (referred to as a basal “plus” strategy) or using premixed insulin analogs for patients with relatively consistent lifestyles and habits. More-concentrated forms of insulin, such as U-500 insulin, may be helpful for patients requiring very large doses of insulin. The key is to match the insulin regimen to the patient; engage in dialogue to understand the patient's lifestyle, concerns, and skill sets; and develop, through a shared decision-making process, appropriate individualized treatment recommendations. The present review article focuses on the use of insulin replacement therapy in challenging patient cases.

Insulin therapy has been the mainstay of therapy for patients with type 2 diabetes mellitus for the past 90 years. This trend is likely to continue as new formulations are developed to more closely mimic physiologic insulin secretion and to provide patients who have diabetes with more convenient options for integrating this therapy into their lifestyle. The present article reviews how the role of insulin continues to evolve, from its earlier use in the treatment paradigm (even at first diagnosis) to its role in combination therapy with incretin-based therapies, as well as new formulations that provide more-convenient forms of insulin replacement therapy.