Saturday, August 20, 2011

Actos Risks

Many patients have recently seen notices from lawyers about Actos risks.
In fact, if you search “Actos risks”, about all that shows up on the first page are tort lawyer firms looking for business.

So what’s up? Should you stop Actos? What are the risks?

Actos is the brand name in the U.S for pioglitazone. Actos has been available in the U.S. since 1999 for treatment of Type 2 Diabetes. Actos will be available as a generic in about another year. The price should drop by then. Actos is expensive now.

Actos works by making insulin more effective. Another way of stating this is that Actos reduces insulin resistance. Insulin resistance is reduced effectiveness of insulin. Almost all people with Type 2 Diabetes have insulin resistance.

The best treatment for insulin resistance is weight loss. Exercise also helps reduce insulin resistance.

When people with Type 2 Diabetes lose weight and exercise they have much better blood glucose levels and they are healthier overall. The problem is that most neither lose weight nor do they exercise. That’s where drugs come in.

Actos is a very effective drug for blood glucose control.
It does not cause hypoglycemia. And Actos tends to help maintain blood sugar control over years better than pills called sulfonylureas and better than metformin.

Actos can be combined with other medications including insulin. Good glucose control over time means a lower risk of the complications of diabetes.

Improvements in blood lipids often are seen with Actos. The HDL cholesterol and triglycerides improve. And fatty liver improves with Actos treatment.

So those are some of the benefits of Actos. How about Actos risks or side effects?

There were 4 main risks with Actos. Now a 5th has emerged.

There is an increased tendency to weight gain with Actos especially as compared to metformin. Leg edema or fluid with swelling under the skin of the legs is more common with Actos.

There is an increased risk of congestive heart failure with Actos. In one large study of over 5000 patients with Type 2 Diabetes, the risk of heart failure was 5.7 % on Actos and 4.1% with placebo, an inactive pill; that’s almost a 40% higher risk in the Actos users.

Heart failure is impaired pumping action of the heart.
Heart failure is not a heart attack.
Actos is not associated with increased heart attacks.
And no increased risk of death from heart failure has been seen in those on Actos.
Blockage in the arteries appears to be less with Actos than with glimepiride, one of the sulfonylureas.

The cause for the increased heart failure with Actos is not clear. It probably relates in part to the fluid retention or edema that can occur from Actos. For most patients, heart failure is not a problem. In that large study of over 5000 people, about 95% did not develop heart failure. And they were at fairly high risk of developing it for many reasons.
Keep in mind that diabetes itself, regardless of medications, increases the risk of heart failure.

The risk of fractures, broken bones, is higher for post-menopausal women taking Actos. That risk appears to be up to 2 fold higher in women on Actos compared to those not. Measurement of bone density is important in these women taking Actos.
I make sure that vitamin D levels are adequate for all my patients.

That brings us to the most recent Actos risk reported. A recent study conducted in France suggested an increase in bladder cancer. Bladder cancer appeared to be about 10-15% more frequent in Actos users versus non-users. Actos remains on the market in Europe.

Overall the risk of bladder cancer is very low: in one analysis, only 19 people developed urinary bladder cancer out of 12,506 who were taking Actos for years.

Another analysis was recently published  that examined bladder cancer in Actos users versus non-users in northern California. This study included 30,173 Actos users versus 162,926 non users of Actos. They found that those who used Actos more than 2 years were more likely to have bladder cancer.
But how much more likely?

They calculated an incidence rate of 69 cases of  bladder cancer out of 100,000 people treated each year who had Type 2 Diabetes and never used Actos. This number was lower than the 103 cases of bladder cancer in 100,000 people taking Actos for more than 2 years.

95% of the bladder cases in Actos users were at an early stage. The authors of this study could not fully account for factors that are known to increase risk of bladder cancer, like smoking.
So that means, there could have been, for example, more smokers in the patients taking Actos. And that could explain the differences that were seen.
 
More will be learned as this group of patients is reported on again next year.

For now, it is best to avoid Actos in those with a history of bladder cancer or heart failure.
All drugs for diabetes have their pluses and minuses.

No drug is perfect. I find Actos to be very helpful for many of my patients.

Good glucose control over time means a much lower risk of blindness, nerve damage and kidney failure from diabetes.

Before starting any new medication, I always discuss the risks and benefits with each patient.
How each person feels about the options discussed helps me to decide what might be best for that person. No one drug is good for all patients.

Fortunately, we have a fair number of drugs to choose from.
Our goal is to provide the best care for each person we see.
I hope this update helps you.

Your Diabetes Endocrine Nutrition Group

3 comments:

  1. Eli Lilly Zyprexa can *cause* diabetes.

    I took Zyprexa a powerful Lilly schizophrenic drug for 4 years it was prescribed to me off-label for post traumatic stress disorder was ineffective costly and gave me diabetes.
    Eli Lilly's #1 cash cow Zyprexa drug sale $40 billion dollars so far,has a ten times greater risk of causing type 2 diabetes over the non-user of Zyprexa. So,here we have a conflict of interest that this same company also is a big profiteer of diabetes treatment.

    -- Daniel Haszard

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  3. Very good points. Anti-psychotic drug associated weight gain, glucose intolerance and diabetes are very important and complex issues. Given the concerns with drugs in this class, we ought to be cautious in prescribing and monitor people closely when on these drugs. Weight and glucose problems, in my experience, tend to be reversible. That is they resolve when the drug is stopped. Of course, some people are more likely to get diabetes in any case. Thanks for the comment.

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