We're here at the annual meeting of the Canadian Diabetes Association in Edmonton, a city that was put on the diabetes map with one well-known protocol. There are around 2100 people here, and we've seen some excellent speakers thus far. Some of the highlights of the first two days:
1. Despite the explosion of new drugs for type 2 diabetes, the emphasis here has really been on early and aggressive insulin therapy. Canada is more insulin-centric than the US and of course Byetta isn't approved here yet (although more than a few eager patients are apparently driving to Buffalo to get it). Dr. Hertzel Gerstein, a key thought-leader here, encouraged early glargine use at a sanofi-sponsored symposium this evening.
2. Compliance is a buzz word as well, and Biovail spared no expense in promoting its long-acting release formulation of metformin, Glumetza, at its Wednesday symposium, connecting a lower frequency of dosing with improved patient adherence and improved outcomes. We continue to believe metformin will be key for combination therapy - one major advantage is the safety data over decades - increasingly important in the vioxx era.
3. Novo announced today that its long-acting detemir insulin, Levemir, will be launched in Canada in January 2006. Detemir was approved by the Canadian regulatory body six months earlier than anticipated. It will be available in pen form and will not be sold as a vial, though its introduction in the U.S. near the same time will be as both a vial and a pen. The US is the only region in which vial use is actually increasing. Novo is trying to differentiate its product by stressing that it has lower variability than glargine and less weight gain - pretty key benefits in our view.
4. Surprisingly, we've heard much less about rimonabant than we did at EASD and NAASO, and clincians here don't seem to be as keyed into it. In contrast, sanofi-aventis's Lantus is still a big deal, as it's relatively new in Canada.
5. We look forward to the Saturday morning session on the state of islet cell therapy. Dr. James Shapiro, leader of the Edmonton Protocol, will be presenting an update on islet cell transplantation, while Dr. Greg Korbut will give a side-by-side comparison of adult and embryonic stem cells and their potential applications in diabetes. Check back for updates...
We also address in more detail below two of the first-day symposia: Medtronic on continuous glucose monitoring and Merck on the metabolic syndrome:
#1 Medtronic: Achievement of Treatment Goals Combining Real-Time Glucose Sensing and Insulin Pump Therapy
This symposium combined a presentations on pumps in type 2 patients with a presentation on continuous glucose monitoring.
Dr. Steven Wittlin (University of Rochester) presented on “Reaching Treatment Targets Using CSII in Type 2 Diabetes.” He focused on the spectrum of type 2 diabetes, stressing the fact that patients with LADA, who almost always require insulin (94%), are 10-20% of patients with type 2 diabetes. According to Dr. Wittlin, there are more patients with LADA than there are with type 1 diabetes. Dr. Wittlin suggested that these patients should be on pumps also: “If I can convince you that these patients ought to be on insulin pumps, we’ve just doubled the number of people on insulin pumps.”
Indeed, Dr. Wittlin was quite strong in his support for pump therapy in type 2, one that could obviously expand Minimed’s potential market. We don't think traditional pump use in type 2 patients will take off anytime soon, though we believe disposable pumps have potential to expand the market considerably. Dr. Wittlin addressed the question of whether exogenous insulin might be atherogenic, concluding that it is not - we are amazed this objection is still around. Further, he argued that intensive diabetes therapy might have an effect on beta cell preservation - interesting that this argument is coming around.
He also made an economic argument, stating that “Insulin is cheaper than oral agents, and certainly cheaper than GLP-1 analogs, so far.” He added that, if a patient is on $250 of oral agents per month and $150 in GLP-1, a pump would pay itself off in year - for us, this math raises questions because 1) $4800 is low for the price of a pump and doesn't include cost of disposables, roughly another $1300-$1500/year AND 2) many type 2 patients that go on insulin also remain on some oral or other injectible therapy. We believe GLP-1 combined with insulin will be quite popular, longer term.
Dr. Wittlin explained that CSII can help with postprandial control, arguing that this is an important element of control.
Dr. Wittlin noted that there have been only three studies of pumps in type 2 diabetes. None of these had positive results in terms of outcome. A 2003 study by Raskin et al. of type 2 patients, in which 91% were already on insulin, did not find a significant drop in A1cs. However—and this point was highlighted as the major finding—patient satisfaction surveys showed that they preferred the pump. We wouldn't expect this to be particularly convincing with payors, of course. Dr. Wittlin also advocated for pump use in the elderly - unsurprising to us in terms of his general pump market expansion theme. From our perspective, physiologic therapy is not necessarily equally appropriate in all groups ...
Dr. Bruce Perkins (University of Toronto) presented “Utilizing Real-Time Glucose Sensing and Sensor-Augmented Pump Therapy in Clinical Practice.”
The presentation included scenarios in which glucose sensing had been useful in clinical practice. Several of them were classic examples: an unexplained high morning glucose, which was uncovered to be rebound from nighttime hypoglycemia; a high A1C with good fasting glucose readings that turned out to be long stretches of post-prandial hyperglycemia combined with some worrying hypos.
Dr. Perkins made the point that CGM and CSII in conjunction may improve long-term adherence. He showed the data on the DCCT tightly-controlled group one year after the study’s conclusion, demonstrating that their A1Cs converged with the conventional treatment group. Dr. Perkins proposed that self-management skills require two things: 1) expert knowledge of intensive insulin therapy, and 2) the ability to assess the parameters of success.
Much of the presentation was devoted to case studies. Dr. Perkins showed a sensor augmented pump with bolus calculator. He also discussed the usefulness of the 3-hour screen and trend arrows.
Dr. Perkins showed the GuardControl Trial data as well as a 2004 study by Bode et al. In the Bode study, the Guardian Continuous Monitoring System was used in a 71-subject two-week crossover study. In the alert group, there was 30 minutes less hypoglycemia per week, and the device was found to have 67% sensitivity and 90% specificity.
He noted that one potential concern was information overload, showing that one patient using a sensor had taken 12 injections in one day. While we see information overload as a concern, we believe the degree to which it is ultimately a negative depends on the patient.
He concluded that CGM is well-accepted by patients and appears to have an acceptable impact on the reduction of severe hypoglycemia, glycemic excursions, and A1C.
#2 Merck: Management of Metabolic Syndrome
This session was extremely well-attended, especially given that it was the first session of the conference. The panel featured presentations by pharmacist Scott Simpson (University of Alberta), endocrinologist Richard Lewanzcuk (University of Alberta), and CDE Dorothy Smolek (Regional Diabetes Program). We highlight here three major take-aways from the symposium:
1) The involvement of non-physician personnel is key. The pharmacist highlighted a Canadian study that showed that the average diabetes patient in Saskatchewan sees their pharmacist 14 times per year, while they see a specialist only one time a year on average. As such, the pharmacist has a unique opportunity to help diabetes patients, and in Canada, many pharmacists choose to specialize in diabetes by becoming CDEs as well. We hear a lot about the transfer of responsibilities to non-physicians in the U.S., but in Canada, they’re already there.
2) The complexity of medications is a challenge in the treatment of diabetes. The pharmacist highlighted as well that they can take responsibility for monitoring for drug interactions, as physicians increasingly need to prescribe multiple, multiple medications for diabetes patients: medications for glycemic control, hypertension, cholesterol, etc. According to Dr. Simpson, physicians sometimes fail to pursue aggressive therapy because of the complexity of medication management.
3) Diabetes is “glucose-centric.” This was the first time we had heard this label, and at first glance, maybe it seems obvious—but this is being increasingly challenged. Type 2 diabetes is morphing into something much greater than hyperglycemia, and increasing attention is being paid to lipid problems and cardiovascular risk. This merging of cardiovascular and metabolic has sparked turf wars between specialists, and we heard today about one physician who believes it is more important to treat cholesterol first and glycemia second. Diabetes care has historically concentrated on achieving glycemic control, and this may be changing.
