For centuries, diabetes mellitus has remained a pathologic conundrum, imposing a metabolic wrath destructively ubiquitous and indelibly branded on every medical subspecialty. As a result, diabetes has progressed at an epidemic rate, now affecting approximately 20 million Americans, of whom 6 million are yet to be diagnosed.
1 The condition has invoked a twofold to threefold risk for heart disease in men and a fourfold to sixfold threat to women.
2
With cunning and persistence, researchers have honed their skills and arduously labored to broaden our cache of available therapeutic agents. It is a testament to their creative expertise that the pharmacology now being applied to diabetes represents an assortment of interventional remedies that reflects a diversified array of physiologic mechanisms.
Consistent with the concept of fine wine and the art of viticulture, the past 60 years have engendered some stunning “vintages” with respect to the medicinal breakthroughs in pharmacologic research. Since the discovery of insulin in 1921, medical detectives have methodically investigated a variety of optional pathways by which to address glycemic control.
The 1950s witnessed science taking advantage of an old medieval antidote in the form of French lilac (
Galega officinalis), with the development of biguanides. The investigative effort produced a “harvest” yielding the likes of
phenformin (commercially used in the 1960s), and ultimately
metformin (approved for use by the US Food and Drug Administration in 1995).
3
The 1980s saw “functional diversification” accelerate our insulin arsenal, with the 1990s capitalizing on techniques by which to genetically manufacture the hormone to near-exact in vivo specifications.
From the mid-1990s to the present, investigative science has advanced exponentially by exposing attractive pathways relevant to the maintenance of glycemic regulation. Those uncovered have been admirably illustrated through the refinement of biguanides and subsequent development of α-glucosidase inhibitors, benzoic acid derivatives, and thiazolidinediones.
Our laboratory surveyors of the 21st century have raised the “bar of exploration” even further by engineering a new “crop” of pharmaceuticals distinctly unique and remarkably diverse in character. With the availability of amylin and the incretins, technology has innovatively implemented techniques by which to amplify the properties of endogenous insulin and complement further the remedial advances already in place.
It is with genuine excitement that we offer you the following supplement as a comprehensive overview and perspective on “Incretins: A New Generation of Agents for Treatment of Patients With Type 2 Diabetes Mellitus.” Consistent with the philosophy inherent to osteopathic principles and practice, the content of this literary review underscores the holistic model by which the body “functions as one,” and therefore highlights the interactive link between a distinct regional system and the intrinsic behavioral properties associated with the hormone insulin.