The Annual American Diabetes Conference (Washington D.C., June 9-12)
The Byetta LAR trial releases highly favorable results.
Byetta LAR is the long-release form of Byetta that would only require weekly injections - a huge improvement, obviously, from the twice-daily insulin therapy many type 2 patients follow today. The results of the LAR trial released at ADA were very positive: 45 patients receiving 2.0 mg doses of the drug for 15 weeks showed an average A1c drop of 2% and an average weight loss of 8.4 pounds, "with no evidence of plateau". No plateau means huge therapeutic gains are possible with LAR: longer treatment may only mean more glycemic improvement and weight loss. By the end of the trial, a whopping 86% of subjects achieved a target A1c of fewer than 7%. There were no safety issues, and we hear anecdotally that "real world" patients may fare even better than patients in the trials if the Byetta experience offers any clues.
We expect Byetta LAR to be available by 2009, and we believe that about half of the patients on Byetta "classic" will convert to Byetta LAR in the first year alone.
DPP-4 inhibitors, one of which has received FDA approval, generate excitement for type 2 patients.
Incretins are gut hormones that stimulate insulin secretion after meals, and DPP-4 is a natural enzyme that degrades those incretins. So researchers are trying to develop DPP-4 inhibitors that prevent this destructive process in diabetics.
The big two DPP-4 inhibitors that received the most attention at ADA were Januvia and Galvus; Januvia has since received FDA approval, and the same is expected for Galvus later this year.
Our impression is that these drugs won't offer the same kind of weight loss as Byetta, which may be a bit of a disappointment. But they also don't promote weight gain, which puts them a cut above traditional TZDs (Avandia and Actos) and sulfonylureas (Glucotrol and Amyryl, for example). The biggest excitement over DPP-4 inhibitors is the possibility that they may preserve or even regenerate beta cells. Novartis's GLORIOUS mega-trial on Galvus will shed light on this question.
For a complete discussion of the incretin craze, please see our Learning Curve column.
Continuous Glucose Monitoring (CGM) remains a focal point.
In terms of excitement, CGM was second only to incretins at the conference. We expected nothing less. CGM is another step down the road to an artificial pancreas, and several models are now available. DexCom's small and sleek STS (see page 2), Medtronic's Minimed, and Abbott's coming Navigator are the frontrunners. At the conference, new data suggested that the Navigator looks like the most accurate but the Paradigm Real-Time 522/722 is still the only integrated device, which makes it closest to the artificial pancreas. We've heard about the artificial pancreas for years upon years and know you have too - we think we're actually getting closer, especially since JDRF has added some very important funding recently.
Verdict is still out on inhaled insulin.
Exubera, which finally started shipping to patients in September, got a lot of hype, but some physicians would like to see some more years of safety. Sure, Pfizer's four-year trials indicate that side effects on lung function are too small to matter in patients without pre-existing pulmonary conditions. But, truthfully, we'd like to see a 20-year trial before we start lining up. Although physicians mobbed the booth, we think that, in this respect, seeing is different from believing, buying, and prescribing. In fact, besides the safety issue, just seeing the product was a little disappointing due to its cumbersome size: much larger than a dainty asthma inhaler.
Look out for a faster-acting insulin.
The drug company Biodel may have developed an even faster insulin than Novolog, Humalog, and Apidra. Early data at the meeting showed that Viaject worked faster than rapid acting analogs in patients. It was only a few minutes faster, mind you, but time is money! The company is going to test this new drug in 66 centers across the United States. See www.clinicaltrials.gov for more info.
Bad lows may not damage cognitive function.
Researchers have long feared that recurrent episodes of hypoglycemia can impair a patient's cognitive function. But Dr. Alan Jacobson from the Joslin Diabetes Center has been following up with patients from the DCCT for an average of 18 years, and his results show that recurrent severe hypoglycemic episodes had no effect on cognitive function in any of the domains measured: problem solving, learning, immediate memory, delayed recall, spatial information processing, attention, psychomotor efficiency, and motor speed. Phew!
