Put drug development to work for diabetic patients

Drug developers and manufacturers often refer to the unmet need of patients when they introduce new products, but what is unmet need and how do we assess it? One way to address this issue is to refer to public health agency reports on causes of mortality and morbidity. Another is to ask what benefits a treatment can confer on patients and others.

Diabetes affects 9% of the U.S. population and is the seventh leading cause of mortality in the U.S., according to the CDC. However, this does not tell the whole story.

Diabetes contributes significantly to cardiovascular disease and stroke (the first and fourth leading causes of death) and to disability due to kidney and neurologic disease and blindness, as well as vascular insufficiency and amputation.

There can also be unmet needs for people with rare disorders or uncommon severe versions of common disorders. Diabetes is a case in point. Many type 2 diabetes patients do reasonably well when they are prescribed and take their medications to control glucose, blood pressure, and lipids. Many patients with type 1 do well with continuous insulin infusions or multiple injections.

However, there are still other patients who suffer the long-term consequences of diabetes. This unmet need is the result of system, scientific and personal issues.

System issues include the high rate of underdiagnosis (which we have discussed in this column before), and the failure to prescribe or follow up on necessary medications. Other system issues go beyond healthcare provision to public health and socioeconomic concerns that impact diet, physical activity and mental health. The National Diabetes Prevention Plan addresses many of these areas.

Personal issues, such as difficulty paying for healthcare and problems implementing life style changes or adhering to medication are also important, and must be accommodated and supported if we are to make further improvements in diabetes outcomes.

Next: Scientific issues

Scientific issues are another matter. The science-based approach to diabetes follows several broad arcs that are dependent on developments in science and engineering:

1. Basic research has been responsible for the discovery of insulin, and the complex interplay of hormones and external signals that are involved in glucose, fat and related metabolism;

2. Development of specific medications for controlling glucose, blood pressure and lipids has contributed significantly to improved longevity and reduced morbidity for people with diabetes. Drug discovery is dependent on science and also on a bit of luck; and

3. Creation of devices such as pumps and monitors has grown along with developments in computing and materials science. Science tends to move at its own pace and is not linear.

Insulin was first injected into a patient with diabetes in 1922 but sulfonylurea based medications were not discovered until 1942. Metformin was first described in 1922. Two other biguanide medications were developed but with drawn from the market. Metformin was not approved until 1972.

Recently, one pharmaceutical company ended the development program for a new basal insulin based on insulin lispro instead of insulin glargine. Peglispro was unique in that it targeted impacted liver glucose metabolism and transport more than muscle glucose activity. This property, which could have proved valuable through reduction in hypoglycemic episodes, eventually proved the undoing of the drug because it led to increasing fat deposits in the liver.

This illustrates both the complexity of glucose metabolism, but also the difficulty in developing drugs with new mechanisms of action or new, and perhaps desirable, properties.

Over the past several years a handful of new drugs, many in the same class, have been approved for use in diabetes (see graph). The most recent additions have been in the SGLT-2 inhibitor class, which not only have a novel mechanism of action (glucose wasting in the kidney) but which are now proving useful in the treatment of diabetic patients with advanced heart disease.

Although the pipeline is not large, we continue to have progress in meeting needs of patients with diabetes. Over time, we can hope to see new drugs that are easier to use, have fewer side effects, and help to reduce complications over time.

In the meantime, screening, diagnosis, appropriate prescribing, and patient adherence to medication, diet and activity regimens will continue to help many patients with diabetes live a long and healthy life.

NME: New Molecular Entity Drug

Data source: CenterWatch.Com

Edmund Pezalla, MD, MPH, is vice president and national medical director for pharmaceutical policy and strategy, Aetna.