What are doctors and medicine for? To help people achieve better health, and maybe even save some lives, right? Well, over the last decade or so I’ve noticed that certain factions within the medical establishment seem to have, largely, forgotten this. We doctors, it occurs to me, are being asked to put more and more emphasis on controlling indices such as blood pressure, cholesterol and blood sugar levels. The subliminal thought here is that by doing so, we will automatically be improving the health of our patients. But is this really so?
If cyanide turned out to be a very effective blood pressure reducing agent, would it make sense for people to take cyanide every day? Of course not. The reason for using this example is to make clear that just because an agent may help improve blood pressure, blood cholesterol, blood sugar or whatever does not mean it automatically improves health. Modern-day medical history contains a few examples of where drugs which have been touted for their chemical properties that turn out to be, as far a health is concerned, quite useless. For instance, the beta-blocker atenolol which has enjoyed decades of use as a blood pressure reducer, was recently shown to make no difference to risk of important outcomes such as heart attack and overall risk of death . Some drugs, in fact, might even be downright dangerous. For example, cholesterol-reducing agents known as ‘fibrates’ (now, thankfully outdated) have been shown, in healthy individuals, to actually increase risk of death by some 25 per cent .
I was triggered into writing about this issue now by a study published this week in the New England Journal of Medicine which, on the face of it, appeared to herald a major breakthrough in the management of type 2 diabetes . This study compared the effects of the relatively new diabetes drug rosiglitazone (marketed under the names Avandia and Avandamet) and two older drugs (metformin and glibenclamide). The ‘outcome’ that this study focused on was the time it took before treatment with just one of these drugs was deemed insufficient. Using this measure, rosiglitazone came out on top. The press release that I got from the makers of this drug – GlaxoSmithKline (GSK) – heralded this as a ‘landmark study’. In this press release, Dr Lawson Macartney, senior vice president of the Cardiovascular and Metabolic Medicine Development Centre at GlaxoSmithKline is quoted as saying that this study: adds to the growing body of evidence released this year supporting the rationale for incorporating rosiglitazone as a cornerstone of treatment of type 2 diabetes by demonstrating patient benefits in terms of long-term glucose control.
Now, let’s focus less on the rhetoric of one of the GSK’s employees and more on the actual health effects of rosiglitazone. First of all, while it delayed the point at which individuals needed to adjust their medication, the drug did not improve actual blood sugar control much (as measured by levels of ‘glycosylated haemoglobin’ which gives a good measure of blood sugar control over the preceding 2 -3 months). Also, compared to one or both of the drugs it was compared to, rosiglitazone use was related to a significantly increased risk of weight gain, swelling (oedema), bone fractures, and perhaps most worryingly of all, ‘cardiovascular’ complications such as heart failure. And it should perhaps be borne in mind that GSK’s new drug is significantly more costly too.
Put all of this into the mix, and the purported superiority of rosiglitazone looks somewhat diminished. So much so, that in an editorial accompanying this study, Dr David Nathan (endocrinologist at Massachusetts General Hospital in the USA) concludes that: metformin remains the logical choice when initiating pharmacotherapy for type 2 diabetes . You might want to compare this opinion with that of GSK’s own employee, Dr Macartney. Spot the difference?
Pharmaceutical companies may look big and powerful but I reckon their situation is quite precarious. Research and development costs spiral and innovation is slowing down over time. Just this week, Pfizer decided to pull a drug (designed to raised levels of ‘healthy’ HDL cholesterol) in the last stages of development because it increased death rates and heart problems. This as not before Pfizer had pumped some $800 million into the development of this drug. News of this spectacular and unexpected failure wiped some $20 billion off Pfizer’s market value. Ouch. A few years back, the pharmaceutical giant Bayer almost went to the wall when it had to pull an already-licenced cholesterol-reducing drug due to complications.
So, I suppose in the face of these sorts of challenges, it’s no surprise that the pharmaceutical industry is trying to eek more and more out of the products it has. And even when a drug has little or no real value, let’s not be too taken aback when the industry attempts to divert our attention to an ‘outcome’ which appears to put their product in a positive light. The next time a pharmaceutical company unveils a new ‘wonder-drug’, I recommend we all endeavour to keep our eye on the ball.
1. Carlberg B, et al. Atenolol in hypertension: is it a wise choice? Lancet. 2004;364:1684-1689]
2. Studer M, et al. Effect of different antilipidemic agents and diets on mortality: a systematic review. Arch Intern Med. 2005;165(7):725-30
3. Kahn SE, et al. Glycemic Durability of Rosiglitazone, Metformin, or Glyburide Monotherapy. Published at www.nejm.org December 4, 2006 (10.1056/NEJMoa066224)
4. Nathan MD, et al. Thiazolidinediones for Initial Treatment of Type 2 Diabetes? Published at www.nejm.org December 4, 2006 (10.1056/NEJMe068264)