ADA: SGLT2 Inhibitors Match GLP-1 RAs for A1c Reduction, Weight Loss

June 25, 2013

Sodium-glucose linked transporter 2 inhibitors lower renal threshold for glucose transport, cause glycosuria, improved glycemic control, weight loss.

Another busy day at the ADA. I started with oral presentations about hypoglycemia-a complication of diabetes therapy that poses significant risks. Most of the information was quite technical, but the session was a reminder that we're seeing more and more emphasis placed on understanding-and avoiding-hypoglycemia.

Mid-morning began another round of awards for scientific achievement and diabetes education. While the specifics aren’t of too much interest here, what is important is how much research and educational effort is being expended to deal with diabetes and possibly even establish a cure.

I spent 3 hours reviewing all the poster material today. There were thousands. Many dealt with the dipeptidyl peptidase-4 (DPP-4) inhibitor class-establishing the  efficacy and safety of these agents as monotherapy and investigating them as add-on to traditional oral agents and as an add-on to insulin. The data from the few safety posters suggest that there is little evidence for concern about pancreatitis or pancreatic cancer with this class.

There were also a number of studies presented on the sodium-glucose linked transporter-2 (SGLT2) inhibitors. This is a new class of medication and became commercially available as canagliflozin (Invokanna) in late March. The SGLT2 inhibitors lower the renal threshold for glucose passage and, thus, cause glycosuria, improved glycemic control, and weight loss of the order seen with glucagon-like peptide-1 receptor agonists (GLP-1RAs). The data presented show that they lower A1C about a full percentage point by lowering the FPG and PPG. While there is some reduction in vascular volume, there is less reduction of GFR than might be expected. Some posters suggested that such GFR changes were only transient and that rates soon return to baseline. The increased glycosuria does lead to increased UTIs and mycotic GU infections but these do not seem to cause much limitation to continuation of the drug.

Many lixisenatide and liraglutide (both GLP-1 RAs) posters were on view along with posters describing these products in use with basal insulin. As mentioned in my earlier bulletins from the ADA meeting, it seems clear that the future trend will be the concomitant use of basal insulin and GLP-1 RAs to control both FPG and PPG to improve glucose control. The combination does not seem to introduce severe hypoglycemia and even leads to weight loss.

My favorite session of the day featured Drs Vivian Fonseca and Paresh Dandona debating the answer to the question of what to do after oral agents have failed. Dr Fonseca supported the use of a GLP-1 RA and Dr Dandona supported the addition of insulin. They did agree that if the A1C is low enough (usually <8.5%) a GLP-1 RA could be added to the orals. If the A1C is higher (>8.5%) it is s more likely that basal insulin will be effective. What I think was most important was that at the end of their respective talks each felt that ultimately clinicians would be using these products in combination.

Tomorrow is the wrap up day, although the vendors have left and the posters have been taken down already. I’ll start off with an interesting morning symposium on obesity management for the practicing clinician. Also, there will be some presentations on new aspects of DPP-4 inhibition. More from me tomorrow!

Charles F. Shaefer Jr, MD
6/24/2013

  Scroll down for links to blogs from the rest of the ADA meeting.