Insulin first became available for use in 1922 after Banting and Best successfully treated diabetic patients using pancreatic extracts.13 In an attempt to more closely simulate physiologic conditions, additional “designer” insulins with unique kinetic properties have been developed, including a rapid-acting insulin that mimics baseline (before meals) insulin secretion, known as lispro.81,157 The hypoglycemic activity of a sulfonamide derivative used for typhoid fever was noted during World War II, and verified later in animals.90 The sulfonylureas in use today are chemical modifications of that original sulfonamide compound. In the mid-1960s, the first-generation sulfonylureas were widely used. Newer second-generation drugs differ primarily in their potency.
Although insulin is widely used for treating diabetes mellitus, oral hypoglycemic exposures are more commonly reported to poison control centers than are insulin exposures, based on 15 years of data from 2001 to 2015 (Chap. 130). In an older review of 1,418 medication-related cases of hypoglycemia, sulfonylureas (especially the long-acting chlorpropamide and glyburide) alone or with a second hypoglycemic accounted for the largest percentage of cases (63%).147 Only 18 of the sulfonylurea cases in this series involved intentional overdose. However, hypoglycemia is reported in as many as 20% of patients using sulfonylureas.73 In a study of 99,628 emergency hospitalizations for adverse drug events in adults older than 65 years, 14% were due to insulin and 11% were due to oral hypoglycemics. The majority (95%) of the hospitalizations related to insulin and oral hypoglycemics were due to hypoglycemia.24 Other causes of hypoglycemia are listed in Table 47–1.
TABLE 47–1Xenobiotic and Non Toxicologic Causes of Hypoglycemia ||Download (.pdf) TABLE 47–1 Xenobiotic and Non Toxicologic Causes of Hypoglycemia
Chronic myelogenous leukemia
Panhypopituitarism (Sheehan syndrome)
Acute hepatic atrophy
Galactose or fructose intolerance
Glycogen storage disease
Chronic kidney disease
Acquired immunodeficiency syndrome (AIDS)
Muscular activity (excessive)
Postgastric surgery (including gastric bypass)
Protein calorie malnutrition
Systemic lupus erythematosus
Carcinomas (diverse extrapancreatic)
Multiple endocrine adenopathy type 1 Sarcomas (retroperitoneal)
The biguanides metformin and phenformin were developed as derivatives of Galega officinalis, the French lilac, recognized in medieval Europe as a treatment for diabetes mellitus.11 Phenformin was removed from the US market in 1977 because of its association with life-threatening metabolic acidosis with an elevated lactate concentration.
Development of the α-glucosidase inhibitors began in the 1960s when an α-amylase inhibitor was isolated ...