By Athena Philis-Tsimikas, MD, Scripps Health
In 1920, a Canadian surgeon by the name of Dr. Frederick Banting decided to test a theory. He believed that diabetes might be related to the function of the pancreas. Two years later, Banting and his assistant tested their insulin extract on their first human subject, a 14-year-old boy with severe diabetes who was close to death. The boy responded positively to the insulin treatments, as did other volunteers. Through further researcher, Banting found that adjusting blood glucose levels helped the insulin work more effectively. For the first time in history, doctors had a treatment for diabetes, and in 1923 Banting was awarded the Nobel Prize in Physiology or Medicine. In 1924, Scripps Metabolic Clinic in downtown La Jolla became one of the first sites on the West Coast to offer insulin therapy.
Since Banting’s initial discovery, diabetes treatments have steadily improved. The first oral medications created for patients with type 2 diabetes were designed to stimulate the pancreas to produce more insulin, thereby increasing the amount of insulin in the bloodstream and lowering blood glucose. These medications were known as sulfonylureas and included Glucotrol and Diabeta. A more effective generation of insulin-producing oral medications followed, marketed under the brand names Prandin and Starlix.
While these insulin-producing medications were effective when combined with diet and exercise, they also posed the risk of reducing blood sugar to dangerously low levels. In addition, patients had to be capable of producing at least some insulin on their own in order for the drugs to work.
It was not until the early 1990s that pharmaceutical companies began releasing new diabetes medications into the U.S. market. Over the next 10 years, a number of drugs were introduced that treated diabetes in various ways when coupled with proper diet and exercise, and many of these are still widely in use today.
Introduced in the 1990s, metformin helps people with diabetes maintain more stable blood sugar levels by reducing the amount of glucose that enters the bloodstream. Metformin accomplishes this by either decreasing the amount of glucose produced by the liver or by temporarily slowing the body’s absorption of glucose.
Thiazolidinediones were also introduced in the 1990s. Known as TZDs, these oral medications address the body’s inability to use insulin effectively to control blood sugar. Marketed under the brand names Actos and Avandia, TZDs temporarily increase the body’s sensitivity to insulin, enabling it to process insulin more effectively. As with earlier drugs, TZDs can be used only in patients who produce at least some insulin naturally. Additionally, the FDA has determined that TZDs may increase the risk of heart attack in people who have heart failure.
In 2006, the FDA approved the first DPP-IV inhibitor, an oral medication that increases the body’s ability to produce insulin when needed by blocking the actions of an enzyme. Glucagon-like peptide-1 (GLP-1) agonists, taken by injection, also increase insulin levels when needed, reduce the amount of glucose produced by the liver and reduce the rate of digestion. As a result, patients may have less appetite and lose weight. Both DPP-IV inhibitors and GLP-1 agonists help glucose remain stable for longer periods of time and have few side effects. Unlike the sulfonylureas used decades earlier, these medications do not increase the risk of hypoglycemia.
Other recent medications include starch blockers such as acarbose, which slows the digestion of food to prevent blood sugar from increasing significantly after meals. Symlin, an injectable medicine used with insulin, also helps to control blood sugar after meals.
Medications continue to be improved and refined. Whereas GLP-1 agonists used to require several daily injections, they are now approved for use just once per week. Newer types of insulin may soon be available that allow much more flexibility; for example, longer-acting insulin can be taken once a day and effectively control insulin levels for eight to 40 hours. Conversely, ultra-short-acting forms of insulin mimic our biological insulin mechanisms by producing insulin within minutes of eating.
Blood glucose testing methods have dramatically changed as well. The first blood glucose meters dated back to the early 1970s and weighed several pounds. Testers placed a drop of blood on a treated paper slip, waited one minute, and then matched the color to a chart to determine their glucose level. Now, blood glucose meters are tiny, computerized and give instant, accurate results.
Insulin pumps, too, have come a long way. In the 1970s, insulin pumps were cumbersome devices the size of a videotape player that people carried on like backpacks. Today, they are the size of a small mobile phone and disposable— patients simply toss them when they are empty. On the horizon are closed loop pumps which detect blood sugar levels every few minutes and deliver insulin accordingly.
Diabetes treatments are improving constantly. Until there is a cure, we will continue to find new and better ways to successfully manage and prevent this disease.