More problems with insulin

I have previously blogged about my concerns with the use of insulin therapy in patients with type 2 diabetes (The Problem With Insulin and The Problem with Insulin- Part 2). Several studies show new concerns using insulin to treat type 2 diabetes. The most notable is the ACCORD study which investigated intensive diabetes treatment and was stopped early because patients in the intensive treatment group had more heart attacks and death. Many experts suspect that even though controlled blood sugar is desirable, blood sugar that is too low may cause problems. This seems to be especially true for insulin, most likely because insulin causes hypoglycemia, or blood sugar that is too low. Hypoglycemia can be dangerous and may explain the excess deaths seen in the ACCORD and other studies. One of the main reasons for my concern is that some recent recommendations from worldwide experts in diabetes suggest that we are not using insulin enough! These guidelines dismiss or leave out altogether newer and potentially safer agents, suggesting that the older (all be it cheaper) diabetes pills which are known to fail over time continued to be used with advancement to insulin once they have failed.

However, a new study from the Lancet gives further evidence to more cautious use of insulin in type 2 diabetes. This UK study looked at two groups of diabetics. One group of about

28,000 patients were already on a diabetes pill (metformin or sulfonylurea) and had their regimen adjusted by adding another pill (metformin plus sulfonylurea). In the second group of about 20,000 patients, patients on one pill that were not under control were either switched to insulin alone, or insulin was added to their diabetes pill. The chart is below, but as you can see the higher your A1c (high A1c means that diabetes is under poor control) is, the greater your chance of death (and heart attack, seen in similar graphs), EXCEPT when your A1c is too low (under 7) and you have a greater risk of death. This is known as a U shaped curve, which means that treatment works, but you need to be careful because over-treatment can cause harm. Both groups saw this effect, but the effect was much greater in the second group that got insulin. In other words, similar to what waas seen in the ACCORD study, if you are on a diabetes pill and you need to get to a goal of below 7, you should probably reserve insulin as a last resort, since it will increase the likelihood of killing you compared to a diabetes pill. In addition, one of the side effects of sulfonylureas is hypoglycemia. It would be very interesting to see how these curves look when non-sulfonylurea drugs such as the TZD's (Avandia, Actos), DPP4 inhibitors (Januvia, Onglyza) or even incretin mimetics (Byetta and just approved Victoza) that DON"T cause hypoglycemia were used. I would suspect the difference would be even greater.

Again, this study lends further evidence that insulin should be used cautiously and other agents should be considered to get diabetes under control before going to insulin. This is in stark contrast to the recently released consensus as mentioned above. I have previously speculated ( here, here, here, and here) why certain experts continue to recommend older drugs and insulin when evidence continues to point to the benefit of some of the newer drugs

Insurance Free Medicine

I never thought I would be in academic medicine for so long. When I was hired about 12 year ago, I figured I would stay in academics for a few years and then join a private practice Internal Medicine group. Now, I can't even fathom that idea. One of the reasons I have stayed at my institution for so long is that I love teaching and the academic environment. However, a second reason is that the "real world" for primary care medicine is a scary one. As a salaried employee in a large practice, I am somewhat sheltered from the harsh realities of running a business in the current health care environment. Yet, I hear horror stories from my colleagues in the community that are struggling to survive. With reimbursement rates from insurances so low, and administrative burdens so high, many older physicians have retired and younger physicians have adopted new models of delivering care. These have various names such as "concierge medicine" or "boutique practices".

Though I have no intention of leaving any time soon, I know that (assuming there are not major changes via health care reform) the current model of a small group of primary care physicians who accept insurance is simply not sustainable. Yet, I have a hard time imagining myself practicing in one of these new models, or even attracting patients to my practice. Retainer medicine is one model, where primary care physicians are able to see a much smaller panel size (and thus increase access) by charging patients an annual fee, which ranges from hundreds to thousands of dollars. Though the model makes financial sense, the word "retainer" sounds too legalese for me and likely not easily understood by the lay public. I would prefer something like "membership fee" similar to something would pay to join a club. However, "membership medicine" or "club medicine" just doesn't seem to have a good ring.

"Boutique" practices often use a retainer model, but boutique can also refer to primary care physicians who charge for extra services such as laser hair removal or botox injections. There are many primary care physicians who still take insurance that have started using these kind of practices or have found other ways to meet their bottom line, such as selling nutritional supplements. Though there is no question that the public has a demand for these services, providing them for a fee as a primary care physician seems to carry some conflict of interest, since none of these services show any benefit in overall health. "Concierge medicine" is another term used with retainer models and boutique practices. This implies some sort of preferential treatment, but also usually is associated with "executive physicals" and a battery of unnecessary testing and high technology that again provides little in the way of proven health benefits.

Some physicians have continued to practice normally, but simply do not accept insurance. They have figured out that they can sustain a primary care practice if they simply refuse to accept the substantially reduced rates that insurance companies give them. These are often referred to as cash only practices. Yet, the term "cash only" seems to imply (at least to me) something shady or under the table. In addition, most patients who see cash only physicians, pay for these services using a credit card, making the name somewhat illogical.

However, the reason that all these new models of medicine exist boils down to one single reason: health insurance. Rates from insurance companies are so low, that the only way a primary care physician can make ends meet is to increase volume to the point that both access and care delivery suffer substantially. In addition, the administrative headaches which include fighting to get tests/medicines covered and arguing over claims once submitted, make the practice of medicine less than enjoyable. The often quoted study (that I co-authored) showing that only 2% of medical students are interested in primary care internal medicine, is often used to support the argument that primary care physicians need to be paid more. While the need to substantially reduce the growing income discrepancy between primary care physicians and specialists is critically important, the study actually showed that educational experience, nature of patient care and lifestyle were the primary factors influencing career choice, not income. This was regardless of students' medical school debt. In other words, it was more about the hassles of primary care medicine and less about the how much money they would make, that led students away from careers in primary care.

Thus, I think a term that I would like to propose for use in further discussions of newer ways of practicing primary care (in blogs, media, etc.) is "insurance free medicine." In my opinion, the term "insurance free medicine" captures the essence of the newer models of primary care. Patients have certainly seen their premiums and deductibles increase and can probably relate quite well to reasons why a doctor would not accept insurance. Insurance free primary care practices could certainly adopt retainer membership fees and promote improved access, but eliminating terms like "boutique," "concierge," and "cash only" might help eliminate the notion that primary medical care without insurance is somehow tainted or only for the super-wealthy. In a previous post on KevinMD, I discussed that without substantial changes, primary care will soon go the way of psychiatry in that patients who use their insurance to see a psychiatrist get one kind of care (very brief visits, mostly management by a non-physician) and those who pay their psychiatrist out-of-pocket get the kind of care that we see in TV and the movies. With a more frequent use of the term "insurance free medicine," patients might start realizing that if they continue to pay their primary physician using their health care insurance, they should expect even briefer visits, longer waits to get in, seeing non-physicians, and greater delays getting a return phone call or results back.

Though I have no immediate plans to leave the world of academia any time soon, I could certainly see starting an insurance-free practice if I ever did.

Why You Should Care About Treatment with Monoclonal Antibodies against Clostridium difficile Toxins

The New England Journal of Medicine just published an article regarding using monoclonal antibodies to treat clostridium difficile toxins (called C.diff). This is a very small study regarding a condition that most people are not familiar with. However, it is very representative of the future of medicine and findings like this have major implications for the cost and delivery of health care.

Monoclonal antibodies are engineered versions of the body's own defense system. They are usually given by injection or infusion. Currently, there are only a few that are used in clinical practice. Remicade (infliximab) is probably the best example, and treats a variety of conditions including psoriasis, arthritis and Crohn's disease. Xolair (omalizumab) is another for asthma. These drugs are not extensively used because of cost, side effects (Remicade can cause serious, life threatening illness) and convenience (Xolair injections are as frequent as allergy shots and no more effective or safer).

C.diff is an intestinal infection that people get after taking antibiotics. Your intestines have normal bacteria that help with digestion (like the Activia adds) and prevent other bacteria, like C.diff from taking over and causing problems. When taking antibiotics you not only kill the bacteria from the infection that is making you sick, you are also killing some of the bacteria that keep you healthy. The stronger the antibiotic(s) and the longer you take them, the more likely you are to get C.diff, which is why we see this in the hospital so often. C.diff is a common complication of a hospitalization, especially if a patient was on antibiotics. In addition, though older, cheaper medications can treat C. diff infections, recurrence of C. diff is not uncommon.
The study in the New England Journal studies 200 patients with a C.diff infection. Half got two monoclonal antibodies to the disease causing toxins made by the C.diff bacteria. The researchers found that the patients who got the antibodies has a much lower rate of recurrence (7% vs. 25%) and re-hospitalization (9% vs. 20%).

The reason you should care about this is because biologics are the wave of the future. Biologics are agents like monoclonal antibodies, blood products, vaccines and gene therapy; that are produced by biologic processes as opposed to chemical processes like most pills that people take today. The days of the blockbuster pills are over. Most pills are generic or will be generic soon. There are very few agents in the drug companies' pipeline. This is why so many drug companies are buying up smaller biotech companies. But more importantly, this is why pharma is so supportive of health care reform and even happy to cover the cost of seniors' medications when they fall into the "donut hole." Pharma realizes that their profits are no longer going to come from single pills that are taken daily by millions of people, but biologics that are taken by a few, really sick people. In addition to potential side effects (often way worse than pills), biologics are very, very expensive. Xolair and Remicade are both about $700 a dose. This does not cover the cost of infusion or injection, which can be quite pricey. Xolair is given every other week for a few years. In the current study, where both groups of patients were already taking the older, cheaper drugs; would it be worth say $1500 extra to reduce the rate of a recurrence by 18%? There are probably about 200,000 cases of hospital associated C.diff infections a year. That's a cost of $300 million! With the rising cost of health care, and efforts to control these costs, be on the look out for biologics.

Comparative Effectiveness: Stroke May Be First

It is very likely that health care reform will pass in the very near future. If you are one of about 30 million who will now get some form of coverage, one of the many patients with pre-existing conditions that fear a job change due to loss of health care, or a senior citizen that struggles with medicine during the "donut hole" period; this bill will have an important impact on your life. However, for most Americans, passage of a health care reform will have no short term effect. In fact, this will essentially be a major first step in hopefully a long series of moves that will positively impact our entire health care system.

One part of the proposed legislation that may have an important impact in the short term for Americans not the aforementioned categories will be comparative effectiveness. I have blogged about comparative effectiveness in the past. Essentially, there is money in the proposed legislation that will have the government do studies comparing two agents or devices to see if the newer medication/device/procedure is worth paying for over the current standard of care. This is extremely important, since most studies regarding treatment are funded by the drug and device companies. Not that these studies don't have merit, but many important studies such as comparing two existing treatments are never done because a negative study is generally not worth the financial risk for the company. See what happened to Merck's stock when the ENHANCE study failed to show that Vytorin was any better that generic simvastatin.

However, there are potential issues to comparative effectiveness as well. Many future decisions on what the government will pay for will be based on this research, and what the government feels is worthwhile may be different than patients with a given disease or condition. The US Preventative Health Task Force is the government agency that recently stated that some mammograms are not worthwhile. There were many women upset about this. The first area that you might see, assuming an agency is set up soon, is with stroke.

Patients at risk for stroke generally take a blood thinner called warfarin. Warfarin is essentially rat poison (not kidding here) that thins the blood, prevents it from clotting, and because of this prevents stroke. It has been proven to save lives. The problem with warfarin is that is has what's called a narrow therapeutic window. This means the dose has to be just right. If the dose is too little, the blood is not thin enough and a stroke could follow. If the dose is too high, a patient could bleed to death. In order to get the dose just right, patients have their blood checked on a regular basis, usually once or twice a month. This is quite inconvenient, but potentially life saving.

A new drug, that will likely soon be approved by the FDA (already approved elsewhere) is called dabigatran. Dabigatran works is a different way so that the blood does not have to be monitored. The heart.org is an excellent source of the latest information in cardiology (need to sign up for free to get the articles). They do a great job of discussing the outcomes of the Re-LY study, which compares dabigatran to warfarin. This was a large study with over 18,000 patients at risk for stroke. The study showed that at the higher dose, dabigatran was better (prevented more strokes) than warfarin, and there was no more bleeding events compared to warfarin, i.e. it was just as safe. In fact, the worse complication feared is hemorraghic stroke (bleeding into the brain) and this was better with the new drug. Thus, the new drug is just as safe or possibly safer, and works better, and patients don't have to go to their physician's office twice a month to get their blood checked for the rest of their lives. Thus, it should be a slam dunk that dabigatran is used over warfarin, right? Here's the problem: warfarin is cheap as dirt, pennies a day; dabigatran will likely be quite expensive, potentially dollars a day. Will the government, based on this kind of comparative effectiveness research, be willing to pay for the better drug? Probably not, since so many patients are currently on warfarin. It will probably come out with something along the lines of that it will pay for it, but only for patients who have problems with warfarin.

In an effort to control health care costs, these are the kind of conversations that you should expect to hear in the not to distant future.