About Insulin and Diabetes

Insulin is a hormone, normally produced in the pancreas, that signals tissues in the body to take up glucose from the blood and store it (or its energy), thereby lowering blood sugar and creating a reservoir of glucose that the body can call on when blood sugar drops. Diabetes is a condition in which an individual has insufficient internally-produced insulin and consequently experiences chronically elevated blood glucose that can cause serious side effects.

In Type 1 diabetes (T1D) the pancreas produces no insulin. Individuals with T1D must inject insulin multiple times daily to stay alive. These injections must be precise – doses must account for current blood glucose levels, planned carbohydrate consumption, planned exercise, and other factors – and precisely timed to account for the time-action profile of the insulin being used. Constant finger-sticks to measure blood glucose and worry about insulin overdose causing hypoglycemia (very low blood sugar) contribute to the significant burden that this necessary therapy places on the 1.25 million people in the United States with T1D.

In Type 2 diabetes (T2D) the body resists the glucose-lowering effects of insulin (called “insulin resistance”), and the pancreas is continually challenged to produce more insulin to keep blood sugar levels in check. While medications that stimulate the pancreas or mitigate insulin resistance help, approximately one-quarter of all T2D patients have progressed to the point where they must supplement their insulin through daily or more frequent injections. More than 24 million Americans have T2D.

Worldwide, diabetes affects 371 million people and is expected to affect 552 million by 2030. The cost of diabetes and its side effects in the U.S. are approximate $245 billion per year.

About Insulin Therapy for Diabetes

Until the 1980s, all commercial insulin formulations were made from either beef or pork pancreata. In 1982, the U.S. FDA approved human insulin for diabetes patients. It was the first drug produced using recombinant-DNA technology and was developed by the first American biotechnology company in collaboration with a large pharmaceutical company. Since then, pharmaceutical companies have at least six novel “insulin analogs” – proteins very similar to insulin but with characteristics that improve on insulin’s therapeutic performance.

Insulin formulations today come in several varieties, many of which rely on the special qualities of insulin analogs. For example, rapid-acting insulins are taken before (or with) meals and used in insulin pumps because they are absorbed quickly. Long-acting, “basal” formulations are taken once or twice a day because they absorb slowly and can provide or augment the needed base level of insulin. Biphasic formulations, containing two physical forms of insulin (in solution and in microcrystals), start acting quickly but have a prolonged tail of action.

Insulin analogs, formulated as a water-based solution, are administered into the subcutaneous fat just below the skin by needle (using a syringe or injection pen; ~85% of people with T1D and almost all people with T2D administer insulin this way) or by micro-catheter connected to a continuous infusion insulin pump. Because the protein is not sufficiently stable alone, insulin formulations contain buffers, salts and other small molecules (called “formulation excipients”) that stabilize the insulin sufficiently to ensure adequate shelf life and patient safety.

Insulin therapy puts a significant burden on patients requiring it; these patients must:

• carry equipment with them everywhere;
• prick their finger to measure their blood sugar with a meter multiple times each day;
• count the expected carbohydrates in each meal before they eat;
• perform a complex calculation each time to determine insulin dose;
• pierce their skin with a needle between one and seven times each day to administer the insulin; and
• worry about the risk of hypoglycemia caused by a miscalculated dose.

This high burden hurts adherence, which undermines blood sugar control, leading to chronically elevated blood sugar levels and resulting in serious sequalae (e.g., kidney failure, blindness, amputations, heart disease, and stroke), leading in turn to very high costs for the healthcare system.

Existing insulin products are all going “biosimilar” (generic) and have significant limitations.  Existing rapid-acting insulins, for example, are not fast enough to optimize the performance of so-called closed-loop pumps (the next generation of insulin pumps that automatically determine insulin dose, thereby lowering the burden on patients and greatly improving blood sugar control) and cannot be used in the concentrated formulations needed for miniaturizing insulin pumps. All insulin products today increase the risk of hypoglycemia because, once administered, they will lower blood sugar even if blood sugar is already low. As a result, patients and pharmaceutical companies recognize a need for improved insulin products that will lower the burden of insulin therapy, enhance patient outcomes, and reduce the overall cost of caring for people with diabetes.

The insulin market today is over $25B/year and is expected to grow to over $70B over the next 15 years as more and more people worldwide get the disease.