We got to Capetown yesterday and today are feeling ever so lucky, and even a little bit ashamed, that we spend so much time talking back and forth about new drugs, new devices .. so much of the world has barely anything. This couldn't be more evident than here at IDF. Yes, the conference center and the city look ever so spiffy, but spend two hours walking through the country federation diabetes booths - Zambia, Ethiopia, Chad - that is ever so unsettling. It makes me so grateful for all the hundreds and hundreds of people that have helped me with my diabetes over time and it makes me grateful to have an HMO (when did I think I would say that?) and to be able to afford rapid acting insulin, to say nothing of Symlin and my STS and my Insulet pods - how lucky could I be?
It is a world of contrasts here, riding in from the airport, watching the shantytowns, then moments later pulling up at a fancy Sheraton, right next door to a gleaming conference center. Of course, we are pulled in right away - there is so much happening here. More new data will be reported nearly every day - tomorrow is ADOPT, then a day off (but some new guidelines), then Sanofi's SERENADE (rimonabant in treatment naive patients with diabetes) then DREAM wash out data. Plus, we already see Merck and Novartis going all out - they have the same time slot for events for Januvia and Galvus on Tuesday - again, we feel lucky we could bring a small team rather than just send one person.
The symposia today were first rate. Roche sponsored talks on continuous, SMBG, and pumps, while Lilly and Novo and Bayer all had top sets of talks - to be sure, there's so much happening. Bayer announced a new trial called ACE that will test Glucobay and look at long-term cardiovascular outcomes - the trial will be led by Dr. Rury Holman of UKPDS (actually, and ADOPT, DREAM, etc) fame, but will be carried out in China. Very interesting! We hadn't realized, but Glucobay is actually approved for pre-diabetes in 25 countries and we assume a positive trial will do much toward gaining that in the US and EU - even though the trial is in China.
Does Novo know how to build interest! It has plastered the town, and its symposium today attracted upwards of 1000 people. What a good chance to discuss novel insulins like Levemir.
On the Lilly front (that was the fourth symposia we attended), interest in Byetta continues to be strong, and if the response here is any indication, while Amylin's stock plummets stateside, we feel more sure than ever about Byetta helping more people. Here are a few outtakes from our time spent at Lilly today:
Dr. Michael Nauck, one of the highly regarded speakers at Lilly's symposium, is widely regarded as an incretin expert. His talk began with an overview of the incretin effect and incretin hormones, after which he presented some clinical data on exenatide, liraglutide, and the DPP-4 inhibitors, offering valuable comparisons of these various therapies.
• In Dr. Nauck’s opinion, loss of the incretin effect in type 2 diabetes patients is not caused by lower incretin secretion so much as a defect in the way these hormones act on the pancreas. This, we thought, was an interesting position because it implies that simply restoring physiologic levels of GLP-1 (as DPP-4 inhibitors do) may not work as well as infusing pharmacologic levels of GLP-1 receptor agonists (as exenatide therapy does).
• Dr. Nauck favored GLP-1 agonists over DPP-4 inhibitors in his comparison of the two: he noted that longer-acting incretin mimetics lower A1C substantially more than DPP-4 inhibitors and cause progressive weight loss as opposed to weight neutrality. The higher hypoglycemia with exenatide depends on co-medication – GLP-1 alone does not cause hypoglycemia, as it is glycemic-dependent. Other differences between GLP-1s and DPP-4s are the injection vs. tablet form and pharmacologic (6x) vs. physiologic (2x) concentrations of GLP-1 restored (with exenatide vs. DPP-4 inhibitors, respectively).
Dr. John Buse, incoming ADA president and another very highly regarded name in the diabetes field (it doesn't get higher actually) gave a slightly more clinical angle on incretin therapies, though he covered most of the same ground as Dr. Nauck. He emphasized the weight loss advantage for exenatide as compared to the DPP-4 inhibitors and reviewed exenatide LAR data. He seemed very optimistic about LAR because of the weight loss advantage and greater A1C drop.
- Dr. Buse noted that many people think incretins should have been a fourth second-line therapy in the ADA/EASD algorithm for treating type 2 diabetes – we certainly think so and thought it a little bit, well, lame that the group decided there wasn’t enough yet data to feature the new class anywhere in the line up. (Clearly, far be it from us to say - this is just our patient perspective as always.) He said he thinks GLP-1 has a good potential future indication with TZDs. In the US, exenatide is considered competitive with insulin, but oral medications are still preferred. He reviewed data from EASD showing that exenatide lowers A1C comparably with premixed insulin and flattens glucose profiles more. (He didn’t mention it, but as many readers know, it has also been shown exenatide compares favorably with Lantus in terms of glycemic reduction and wins out on the weight loss side.)
- Dr. Buse said that weight loss is “what has really captured the hearts and minds of US physicians.” In an open-label extension of exenatide phase 3 trials, patients had sustained progressive weight loss of 5% body weight through 104 weeks. In contrast, sitagliptin is weight neutral, though it is not associated with GI side effects and does not cause antibody formation. Again, although he didn’t mention it, we also know that three-year data with a smaller number of patients taking exenatide showed durability of A1c reduction and increased weight loss versus year two (which has been an increase over year one).
- Regarding vildagliptin, Dr. Buse said, “I don’t know whether it will be approved by the FDA or whether it will have a broader set of indications but we should know that very soon.” Interesting to us he didn’t mention side effects, since that was the original reason for the delay.
- On the initial exenatide LAR trial, Dr. Buse hypothesized that the reason there was no weight loss on the 0.8 mg dose but a very large weight loss on the 2.0 mg dose is because weight effects are associated with the level of GLP-1 activity and the lower dose was below the threshold for weight loss but above threshold for glycemia effects (which made sense to us and we assumed this is probably also the case for DPP-4 inhibitors).
The Q&A session for the incretin section of Lilly’s symposium was quite interesting, with all three panelists giving their opinion on topics including the role of SFUs, choosing between exenatide and DPP-4 inhibitors, where incretin therapies fit into the algorithm for type 2 diabetes, and whether exenatide has a role in type 1 diabetes. Other topics included clarifications about weight loss, cost, beta cell mass, diabetes prevention, and what long-term studies should be done next on incretin mimetics. Fascinating, and we'll have updates in DCU and diaTribe next issues...
All for now, in the meantime ...
Kelly, another great report. Your insights are much-appreciated by very many. All the best.
p.
Posted by: Paul B | 12/05/2006 at 04:39 AM