Pharmacological Management of Diabetes Mellitus: A Century of Expert Opinions in Cecil Textbook of Medicine.

Background: Drug therapy for diabetes mellitus (DM) has had a significant impact on quality of life and work potential of affected persons and has contributed to a remarkable decrease in the frequency and severity of complications, hospitalizations, and mortality. The current approach is the result of incremental progress in using technological advances to increase the safety and effectiveness of insulin therapy and the introduction of new molecules as oral and injectable antidiabetic drugs.

Study Question: What are the milestones of the changes in the expert approach to the pharmacological management of DM in the past century?

Study Design: To determine the changes in the experts' approach to the management of DM, as presented in a widely used textbook in the United States.

Data Sources: The chapters on describing the management of DM in the 26 editions of Cecil Textbook of Medicine published from 1927 to 2020.

Results: In 1927, DM was treated with insulin extracted from the pancreas of large animals (cattle, hogs, and sheep) and purified with alcohol to prevent the tissues' proteolytic action on the hormone. The therapeutic milestones in DM marked 2 avenues for innovation. The first created advances in insulin therapy, starting with processes that led to the production of crystalline insulin and protamine zinc insulin (1937), synthetic human insulin (1996), and prandial (2000) and basal (2004) insulin analogues. The second was an effort to develop and introduce in clinical practice in the United States oral antidiabetic drugs, starting with tolbutamide, a sulfonylurea (1955), followed by metformin, a biguanide (1996), thiazolidinediones, alpha-glucosidase inhibitors, and benzoic acid derivatives (2000), dipeptidyl peptidase-4 inhibitors and glucagon-like peptide 1 receptor agonists (2008), and sodium glucose cotransporter 2 inhibitors (2020). A latent period of 40 years between significant advances was likely because of searches for new technologies (eg, recombinant DNA for the production of synthetic insulin and analogues) and, at least in part, to the impact of the controversial University Group Diabetes Project on the development and acceptance of oral antidiabetic drugs.

Conclusions: The pharmacological management of DM has progressed unevenly, with a long latency period in the second half of the last century followed by highly encouraging advances in the first 2 decades of the 21st century. In chronological order, the major advances were synthetic insulins obtained through DNA recombinant technology, adoption of metformin as first line therapy, and introduction of antidiabetic medication classes that also promote weight reduction and cardiovascular health.