Contemplating pioglitazone

A question that's been on my mind for literally years now.

Of all the conditions that plague those denizens of the overdeveloped world, the umbrella of fatty liver—nonalcoholic fatty liver disease (NAFLD) and the more serious nonalcoholic steatohepatitis (NASH)—has the fewest pharmaceutical options available. Heart disease? Drug options are legion. Type 2 diabetes? I could list them...how many hours do you have? But for fatty liver, the legit options basically come down to diet and weight loss. Some drugs are coming down the pike, but virtually nothing exists at this time.

I say virtually because there is one drug that is a possibility for people who have NASH that has been diagnosed via liver biopsy. Pioglitazone, also known by its brand name Actos, is a drug mainly used for type 2 diabetes. It has been shown in a number of trials to be effective at reducing fat deposits and potentially inflammation in the liver, both in people with and without type 2 diabetes. It is a "glitazone," or more accurately, a thiazolidinedione drug. It improves insulin sensitivity. It acts on peroxisome proliferator-activated receptors, known as PPARs. They increase glucose intake in peripheral organs and decrease gluconeogenesis in the liver.

But for now, let's cut a bit more to the chase.

History and Current Status

In August 2015, I was officially diagnosed with perhaps the least severe form of NASH possible. Biopsy demonstrated very minimal, but definite fibrosis or perhaps scarring of the liver. Yay. By that regard, I qualified for being placed on pioglitazone, if seen as appropriate. It's not a trigger drug; by that, I mean a diagnosis doesn't automatically mean to go on the drug. Try diet and weight loss first, and if that doesn't work, then consider it.

For obvious reasons, weight loss hasn't been quite the best way to go about addressing this for me. I like being big, and so I wanted to have my cake and eat it, too. From 2015 to 2022, my weight has been fairly constant, around 285-290. In August 2022, I began doing intermittent fasting, and between then and the end of the year, I lost roughly 20-25 pounds. Since then, I've been at the same weight. Went off intermittent fasting, put on a few pounds and began feeling worse. Then started again, and am slowly losing weight again and feeling a bit better. I did a 40-hour fast, then made the mistake of enjoying a full pizza as my second meal after ending the fast. My liver/gallbladder rebelled painfully; this made me feel like maybe things had worsened to the point where I could use some extra help. I'm currently around 267 pounds.

I'm currently taking vitamin E, 400 IU bid, indicated for NASH. Also am taking...um...some amount of alpha lipoid acid qd. Occasional milk thistle, probably too occasional to be of much use, but I can boost it.

Ads/DAs

The advantages are obvious. Documented reduction in liver fat deposits. Potential reduction in inflammation. And one of the probable interesting benefits (at least for me): virtually guaranteed weight gain. But the improvement to liver health and all that entails is most significant. If cirrhosis or liver cancer were to happen, pioglitazone could forestall or even prevent it.

Disadvantages, unfortunately, do exist. It is not the best tolerated drug out there. Horror stories of bad effects abound. Obviously people are not happy with weight gain, which might be less of an issue with me. But other issues like ankle edema, heart problems, fatigue, other liver issues, tooth issues, and even a remote risk of bladder cancer are possible with this drug. None of these are guaranteed. There is always the possibility that none of these occur, but some may occur. Seems that edema is the most possible/probable occurrence.

I'll be honest: I vacillate on this question hugely. One possibility is I do a trial run and see how I react to it. If I'm okay, then I stick with it; if not, I drop it, no further obligation necessary.

Interesting side note: pioglitazone in high doses may have benefits on behavior and other related symptoms in autism spectrum disorder. It would be very interesting and slightly amusing if I were to see improvement in certain symptoms here if I were to take pioglitazone.

Well, this is not the end of this. I'll be talking with my doc in a week about this.