Diabetes Treatment: Increasing Complexity and Cost

Dr. David J. Holcombe
Dr. David J. Holcombe

Diabetes has increased parallel to the epidemic of obesity in the United States.  It now affects over 10% of the adult population, many of whom are unaware they have the disease.  Diabetes contributes to strokes, heart disease, neuropathy, renal failure, blindness, peripheral vascular disease and amputations.  The morbidity and mortality continue to soar as does the price tag for treatment, which reached $245 billion dollars a year in 2012 (around 20% of the healthcare budget).


While Americans seems to have become more health conscious, the ubiquitous presence of processed foods, fast foods, sugary drinks, plus the limited opportunities for physical exercise in general have created the perfect storm for promoting obesity and developing diabetes.


Traditionally, diabetes has been divided into “insulin dependent” and “non-insulin dependent”.  The former is “juvenile onset diabetes” which is an autoimmune disease that destroys the body’s capacity to make insulin.  The non-insulin dependent group were traditionally adults, mostly overweight, whose body cannot produce enough insulin for their increased needs (but who often have higher than normal amounts of endogenous insulin) and must take various oral agents.


The distinction between these groups has become blurred in recent times with many “adult onset diabetics” beginning in children and adolescents, and many of these patients requiring supplemental insulin, in addition to other medications.  The first line of treatment, diet and exercise, associated with significant weight loss, proves unattainable for many diabetic patients.


The dramatic increase in diabetes has been associated with an impressive increase in the number of new non-insulin treatments, many of them with hefty price tags.  What follows is a brief review of some of the non-insulin medications, along with their mode of action and administrations.  The names here are the scientific rather than brand names.  A quick look on Google will help you navigate the many brand names.


  1. “Secretogogues” are oral medications that promote insulin release from the pancreas. This group includes Glimeprimide, Glipizide and Glyburide, and the Glitinides (Replaginide and Nateglinde).


  1. Biguanides, such as Metformin, decreases liver production of glucose. Rosiglitazone and Pioglitazones (Thiozolidinediones) increase the body’s sensitivity to its own insulin.  They are taken orally.


  1. Alpha-Glucosidase Inhibitors are taken orally, but are not absorbed by the digestive track. In the gut, they slow the breakdown of carbohydrates into glucose. This group includes Acarbose and Miglitol, both can cause significant digestive symptoms, including bloating and diarrhea.


  1. DPP-4 Inhibitors block the enzyme that degrades GLP-1 (Glucogan-Like Poly peptide), an incretin, a substance that stimulates insulin production in the pancreas. This group includes the oral agents, Sitagliptin and Saxagliptin.


  1. GLP-1 Analogs act as a synthetic incretins, which enhance insulin secretion, but also delay gastric emptying, reduce liver fat and decrease appetite. Exenatide and Liraglutide, are GLP-1 Analogs, and both require injection.


  1. Amylin Analogs (Pranlintide) are injectable, and act by decreasing appetite, slowing gastric emptying and reducing liver output of glucose.


  1. Last but least, there are the Sodium-Glucose Linked Transporter (SGLT-2) Inhibitors, which inhibit glucose re-absorption in the kidney by about 90%. The inhibitors are called Glifozins and the first available agent was Canoglifozin.  Use of this agent requires a normal functioning kidney and its recent release means that its long-term safety remains to be established.


In addition to these single agents from these various classes, there are hosts of combination medications making use of their complimentary modes of action.  Among all diabetic medications, methods of delivery (oral vs. injectable), modes of action, side effects and price vary wildly from one agent to the next.  Some older medications (such as Metformin) exist in inexpensive generic forms, while the newer agents can cost hundreds of dollars a month.


This amazing diversity of treatment options can be daunting for the physician and both confusing and expensive for the patient.  Direct advertising, aggressively promoting newer medications, is certainly not the best method by which to choose, either for the patient or the physician.  The multiple billion-dollar diabetic drug industry, while responding to our increasing need for diabetic medications, should not make anyone forget the fact that significant weight loss and dietary modifications can greatly help the average diabetic achieve control, often without the need for medications at all.