On-Site at the ADA: Initial Triple Therapy for T2DM?

June 24, 2013

Initial triple-agent therapy for type 2 diabetes, compared with step-wise add-on therapy, produced a durable drop in A1C.

This mornrning, John Anderson, an internist and president of the ADA, delivered his address. He focused on the shortage of primary care providers and endocrinologists who are and will be available to treat type 2 diabetes (T2DM). His lecture also revealed the lack of funding for diabetes research, especially compared to other chronic diseases.

All of this is a complex problem with no immediately clear solution. Dr. Anderson said medical students should be shown primary care for the rewarding profession that it is. He urged that some way be developed to overcome the overwhelming educational debt so many students accumulate. And he recognized that NPs and PAs will play an increasingly important role in provision of diabetes care. These are critical and enduring themes that face all of us today.

The Banting Award for Outstanding Scientific Achievement went to Graeme Bell, PhD. He has done outstanding work on the genetics of insulin and diabetes. He raised the interesting possibility that some “diabetics” may have only genetically elevated glucose set points and no disruption in actual metabolic control at all.

Today was a day to take in some posters and I was drawn to the area of new therapies and incretins.  A poster by Gokhale and associates titled Dipeptidyl peptidase-4 inhibitors and comparative pancreatic cancer risk was of particular interest. The gropu looked at close to 19,000 DPP-4 inhibitor initiators. The authors found no increased incidence of work-up for pancreatic cancer (PC) or incidence of PC in dipeptidyl peptidase-4 (DPP-4) inhibitor users compared to thiazolidinediones (TZD) or sulfonylurea (SU) users.

Abdul-Ghani and colleagues looked at initial triple therapy compared with add-on conventional therapy in patients with newly diagnosed type 2 diabetes. This is an idea carried forward from Dr. Ralph DeFronzo’s Ominous Octet Banting lecture 5 years ago wherein he proposed the use of metformin+exenatide+TZD for initial T2DM therapy. Abdul-Ghani et al, showed that in the triple therapy group the A1C was reduced to the same degree as with add on therapy, but the initial drop in A1C was preserved during the 2 years of the study. The add-on group had a 0.5% rise in A1C over the 2 years of study after an initial drop. Compared to the add-on group, triple therapy patients had a 13.6-fold greater reduction in hypoglycemia and -1.2 kg weight loss vs. 3.6 kg gain among the add-on patients. I’m sure we’ll hear more about this in the not-too-distant future.
 
Finally, for now, Koro and associates reported on the current use of GLP-1 RAs and DPP-4 inhibitors. They found that these drugs are used mostly as add-on agents with only 8% of GLP-1 RA prescriptions going to new users vs 15% of DPP-4 inhibitor prescriptions. This suggests that most prescribers are much more likely to use a DPP-4 inhibitor than a GLP-1RA. The discontinuation rate for both classes was high:  80% for GLP-1 RAs and 69% for DPP-4 inhibitors. Clearly we need to further assess why so many patients discontinue these drugs.

Tomorrow is another full day of lectures and posters and I hope to get to the vendor area to see what’s new.

Charles F Shaefer, Jr, MD
6/23/2013 
Scroll down for links to blogs from the rest of the ADA meeting.