The latest effort in this direction was the publication of a new study that is being spun in the media as showing the Actos is far safer than Avandia.
Here's a link to the actual study: Comparison of Cardiovascular Outcomes in Elderly Patients With Diabetes Who Initiated Rosiglitazone vs Pioglitazone Therapy. Wolfgang C. Winkelmayer, MD, ScD; Soko Setoguchi, MD, DrPH; Raisa Levin, MS; Daniel H. Solomon, MD, MPH. Arch Intern Med. 2008;168(21):2368-2375.
The study's finding was this:
After adjustment for a large number of patient characteristics, Cox regression models revealed 15% greater mortality among patients who initiated therapy with rosiglitazone [Avandia]compared with pioglitazone [Actos](95% confidence interval, 5%-26%). Use of rosiglitazone was also associated with a 13% greater risk of congestive heart failure (95% confidence interval, 1%-26%). No differences between the 2 drugs were found in their rates of myocardial infarction or stroke.This makes Actos sound pretty good, doesn't it. But only if you ignore the study design. Let's look more closely at why this is a misleading study.
1. There was no control group of people taking no TZD drug. The finding that Actos causes less heart failure than Avandia sounds like good news until you learn that other studies have found that Actos causes a lot more heart failure than taking no drug at all. In fact, heart failure appears to be a side effect of this class of drugs.
This meta-study discovered the real risks:
Thiazolidinediones and Heart Failure: A Teleo-Analysis Sonal Singh, MD, Yoon K Loke, MBBS, MD and Curt D Furberg, MD, PhD. Diabetes Care, published online ahead of print May 29, 2007
As reported by Bloomberg.com are these:
The analysis in the journal Diabetes Care projected that one in every 50 patients who takes Avandia or Actos over a 26-month period would be hospitalized for heart failure. The researchers found that one-fourth of cases occur in people younger than 60. Heart failure tends to affect older people.Note this comment from the study:
Heart failure can occur even at doses below those used for therapeutic benefit, and the relatively low daily doses of pioglitazone 15-mg or rosiglitazone 2 mg are already at the top end of the dose-effect curve for triggering off episodes of heart failure.
So yes, maybe Actos causes less heart failure than Avandia but it still causes unnecessary heart failure in younger people when taken even at low doses. And it causes heart failure in younger people who did not have cardiac disease before they started taking it.
2. This Study Did Not Look For The Other Well-Known Severe Side Effects of Actos. Heart failure and heart attack are severe side effects, but they are not the only serious side effects associated with Actos and Avandia.
Actos causes macular edema, which leads to blindness. Macular edema is swelling in the retina. You can read about the relationship of Actos to this side effect here:
Medscape: Glitazone Use May Be Associated With Macular Edema in Diabetics
Actos also causes osteoporosis leading to fractures, especially in older women.
This is clearly stated in the Prescribing Information published by the drug's maker:
Fractures: In a randomized trial (PROactive) in patients with type 2 diabetes (mean duration of diabetes 9.5 years),an increased incidence of bone fracture was noted in female patients taking pioglitazone. During a mean follow-up of 34.5 months, the incidence of bone fracture in females was 5.1% (44/870) for pioglitazone versus 2.5% (23/905) for placebo. This difference was noted after the first year of treatment and remained during the course of the study. The majority of fractures observed in female patients were nonvertebral fractures including lower limb and distal upper limb. No increase in fracture rates was observed in men treated with pioglitazone 1.7% (30/1735) versus placebo 2.1% (37/1728). The risk of fracture should be considered in the care of patients, especially female patients, treated with pioglitazone and attention should be given to assessing and maintaining bone health according to current standards of care.The reason for this appears to be that the way that the TZD drugs decrease insulin resistance is by transforming bone stem cells into new fat cells into which insulin pushes glucose. Over time, the bone is weakened because the cells that should have grown into new bone have turned into fat.
Neither macular edema or osteoporosis were investigated in this study. Had they been, it is likely that the finding would have been that Actos caused more of these disastrous side effects.
All These Side Effects and Actos Does Little for Blood Sugar and A Lot For Weight Gain
A study that compared Actos against diet and exercise found that the drug was not as effective as diet and exercise and that, in fact, what it did was add brand new fat cells to people's upper arms and butts.
Effects of Pioglitazone Versus Diet and Exercise on Metabolic Health and Fat Distribution in Upper Body Obesity Samyah Shadid, MD and Michael D. Jensen, MD (Mayo Clinic). Diabetes Care 26:3148-3152, 2003.
This is troubling, because once you add new fat cells, they do not go away even when you diet. It is even more troubling because the Mayo Clinic study cited above also found that The group of insulin resistant volunteers in this study who took no drug but cut 500 calories a day from their diet and exercised for 45 minutes achieved far better improvements in their fasting insulin levels, their fasting triglyceride levels, and their total cholesterol than did the Actos group, while losing weight from both their waists and their "lower fat depot," which is how scientists denote the part of your body that is covered by your undies.
Finally, it is worth noting that the main reason that doctors have been recommending Avandia and Actos for the past decade is because the drugmakers convinced them that these drugs could rejuvenate failing beta cells.
This turned out to be completely false. The follow-up to the DREAM study found that as soon as people who had been taking Avandia for more than 3 years stopped taking it, they became diabetic at the same rate as those did who had not taken the drug. This makes it clear that the drug had no impact on beta cells at all.
BOTTOM LINE: There is NO reason to take either Actos or Avandia. They are both dangerous drugs that make a very small difference in blood sugars at the cost of packing extra fat on you and exposing you to the possibility of developing catastrophic side effects that may shorten your life, make you go blind, or leave you with crumbling bones.
For detailed information about the problems with Actos including links to many peer reviewed studies, including those that proved it did not regrow beta cells as claimed by the manufacturer and that it damages the bones, please read this web page:
Actos and Avandia -- Dangerous Diabetes Drugs