San Diego, CA—During the 2011 Scientific Sessions of the American Diabetes Association (ADA), American Health & Drug Benefits interviewed Robert Henry, MD, ADA President, Medicine & Science, and Chief, Endocrinology Division, San Diego Veterans Affairs Healthcare System, and Professor of Medicine in Residence at the University of California, San Diego.
Q: In the current era of cost containment, and with a wealth of new and expensive drugs available for the treatment of type 2 diabetes, what are current best practices for newly diagnosed patients and for those with poorly controlled type 2 diabetes?
Dr Henry: For new-onset diabetes, lifestyle modification and metformin are the cornerstones of therapy. Metformin has a long track record, with beneficial effects on glycemic control. It is cheap, and it works without significant side effects in about 90% of patients.
For patients with suboptimal glycemic control, therapy should be individualized. One of the problems in treating poorly controlled type 2 diabetes is that the available algorithms are not targeted to individual patients. Not every drug is good for every patient. Certain individuals would benefit more from one drug than another. For example, an obese patient with poor glycemic control could benefit from the addition of a GLP [glucagon-like peptide]-1 agonist to metformin. A patient with less obesity and mild-to-moderate elevation in hemoglobin A1c may do well with a DPP [dipeptidyl peptidase]-4 inhibitor added to metformin.
Other medications are available. Sulfonylureas are not my first choice, because they do not exert their effect for very long and do not spare the pancreas very well. There have been long-standing concerns about the cardiovascular effects of sulfonylureas, although they are not clearly documented. However, sulfonylureas are cheap and effective, and will continue to have a role in the management of diabetes.
Q: What about all the new insulin preparations becoming available?
Dr Henry: These preparations can be valuable for most patients with type 1 diabetes, and for about 20% to 25% of patients with poorly controlled type 2 diabetes who are not responding adequately to oral therapy. Basal and bolus preparations may be needed to optimize glycemic control. Thus, the development of ultra-rapid-acting insulin and insulins that mimic normal physiology are welcome advances.
Q: Are the newer drugs, such as DPP-4 inhibitors, GLP-1 agonists, and SGLT2 inhibitors, really advances for patients?
Dr Henry: The DPP-4 and GLP-1 drugs are advances, because they enable care providers to individualize treatment based on patient characteristics. SGLT2 [sodium glucose cotransporter2] inhibitors are not approved yet, but they have a unique mechanism of action that leads to increased excretion of glucose in the urine. Because of this unique mechanism of action, these agents, if approved, are potentially useful with insulin, GLP-1 agonists, or with any of the oral agents, and they have the added value of modest weight gain.
Q: What are the current unmet needs regarding treatment for patients with type 2 diabetes?
Dr Henry: The biggest gap is a need for effective and safe insulin sensitizers. The drugs that are directed at insulin sensitizing will ultimately be the drugs that most significantly delay progression to diabetes. The thiazolidinediones (TZDs; rosiglitazone and pioglitazone) improve insulin sensitivity by about 30% to 40%, but they have undesirable side-effect profiles. The only identified major mechanism for insulin sensitization is PPAR [peroxisome proliferator-activated receptor]-mediated, and the pharmaceutical industry has backed off from developing new drugs, because of the problems with current TZDs. Hopefully, new basic science insights will encourage the development of insulin sensitizers with a good side-effect profile.
In my opinion, another major gap for type 2 diabetes is compliance, primarily because the drugs are so costly. When money gets tight, many people may stop taking their drugs for periods of time. It may take about a week or 2 for them to start to feel the effects of stopping, but the worsening of glucose levels is immediately doing more damage to their eyes, kidneys, nerves, and other tissues.
Q: What are the major challenges physicians, nurses, and other clinicians face in managing type 2 diabetes?
Dr Henry: Obesity. Weight gain contributes to the pathophysiology of type 2 diabetes. Some of this may be genetically driven and some of it is the individual’s responsibility, but it is also partly due to the food industry and poor choices available to people. Another challenge is getting people to exercise and improve their levels of physical fitness. I see this as a problem of our society, but solutions are being implemented at the community level, and will undoubtedly have benefits for patients.