The American Association of Clinical Endocrinologists (AACE) 16th Annual Meeting & Clinical Congress

The AACE (American Association of Clinical Endocrinologists) took place in early April in Seattle. The main themes, we found, were the lowering of glycemic targets (like A1c) and the growing recognition of the harmful effects of glycemic variability (when blood glucose fluctuates).

Better, tighter glycemic control is always a theme at this meeting. This year, the focus was on postprandial glucose management and the greater use of combination therapy to push A1c values below 6.5 percent. The American College of Endocrinology (ACE) and AACE will soon publish a joint “roadmap” for the prevention and care of diabetes. We were able to get a preview: Compared to the ADA’s guidelines, it will emphasize a lower A1c target as well as the need for patients to receive different treatments depending on their A1c level.

Fasting and postprandial glucose make different contributions to overall hyperglycemia. We note that this is based on the work of Dr. Louis Monnier, who published an important paper in 2003 that showed that post-meal glucose spikes are a bigger contributor to overall hyperglycemia for patients at lower A1c, while high fasting glucose is a bigger contributor for patients at higher A1c. For example, for patients with A1c <7.3 percent, postprandial glucose accounts for 70 percent of overall hyperglycemia while fasting glucose accounts for only 30 percent . The contributions are reversed for patients with A1c >10.3 percent. For patients with A1c between 7.4 percent and 10.3 percent, postprandial and fasting glucose make equal contributions to overall hyperglycemia.

Combination therapy is needed to treat both fasting and postprandial glucose. The logic, then, is that in order for patients to achieve lower A1c targets, they need a combination of treatments that target both fasting and postprandial plasma glucose levels. Examples of drugs that focus on fasting plasma glucose are: basal insulin (Lantus and Levemir), metformin (generic), and sulfonylureas (generic). Examples of drugs that focus on postprandial plasma glucose are: rapid-acting insulin analogs (Novalog, Humalog, and Apidra), pramlintide (Symlin), exenatide (Byetta), DPP-4 inhibitors (Januvia), and thiazolidinediones (Actos and Avandia). ACE/AACE recommends that diabetic patients achieve fasting plasma glucose <110 mg/dL (pre-meal) and postprandial plasma glucose <140 mg/dL (post-meal).

The ACE/AACE roadmap will include newer drugs. The ADA currently recommends metformin and lifestyle intervention (diet and exercise) as first-line therapy for patients diagnosed with type 2 diabetes, in order to achieve a target A1c <7 percent. For patients who still remain uncontrolled on metformin alone, it recommends adding a sulfonylurea, thiazolidinedione (TZD), or basal insulin. The ADA’s algorithm does not endorse newer drugs like Januvia or Byetta. However, in sessions at AACE this year we learned that the ACE/AACE roadmap will likely include more options for first-line therapy, including Januvia, and that it will also include other postprandial-specific drugs like Byetta and Symlin as additional therapeutic options for patients who are not at A1c goal on one drug alone.

There was a lot of focus on earlier insulin use as well as moving toward more use of meal-time insulin. Some research suggests that early use of insulin – at diagnosis of type 2 diabetes, even – can have long-term effects on reducing complications. Sanofi-Aventis is currently conducting a 12,500-patient 5-year trial called ORIGIN to determine whether early use of its basal insulin, Lantus, can delay the development of type 2 diabetes in people with prediabetes, or whether basal insulin can delay the development of complications in people with early type 2 diabetes. The trial results will likely be unveiled in 2010. Speakers at AACE also advocated earlier use of meal-time as well as basal insulin – this hearkens again to Dr. Monnier’s work, which showed that controlling mealtime glucose excursions is crucial for people at lower A1c’s.

Lots of focus on driving down A1c targets – some well-known endocrinologists recommended A1c <6 percent. This underscores the importance of achieving near-normal glucose targets – we thought it was great to hear a respected endocrinologist like Dr. William Cefalu actually say this. His whole point was that traditional drugs increase insulin action (metformin, TZDs, sulfonylureas, and insulin itself), but the new ones reduce glucose production (Byetta, Symlin, and Januvia), which should really help people achieve near-normal blood sugars. He gave a dramatic talk about how incretins are exciting because they may alter the natural history of diabetes by improving beta cell function and perhaps slowing what we used to think was the “inevitable” progression of disease in type 2 diabetes. Only time (and longer clinical trials) will tell whether these drugs can actually do this.