Gout and Obesity

Hi, I'm Jack Cush with RheumNow. In this video, we're going to discuss obesity and gout. Can you think of two diseases that fail to reach their target as much as gout and obesity? Are these then not the two most difficult disorders to manage in primary care and in rheumatology? Is it surprising that they are so intimately connected? They both have dietary issues. They both have behavioral tie-ins. They both when not well-managed end up in cardiovascular risk if not death. So gout is a substantial problem in the United States as is obesity, and having both leads to significant medical consequences.

The thing about it is that gout is treatable and that obesity is the strongest modifiable risk factor for gout. So we do know that as your BMI goes up, for every unit above 25 — the upper limit of normal — there's a 5% increased risk of gout for every one unit of BMI. 70% of gout patients are overweight or obese. So when you're considering gout, we often talk about obesity as being one of the comorbidities. It's not the most common one. The most common one is probably metabolic syndrome in three quarters, and hypertension and renal disease in 70% or more. But obesity is at least present in 53–54%. And again, important because that's a modifiable risk factor through behavioral interventions.

It is nonetheless interesting that as I have slides on gout and its prevalence — I think it started at a prevalence of 8.3 million in the United States, and then it went up to nine something, and it went to 10.1. The most recent prevalence statistic is 12.1 million Americans have gout. What's happened in these different eras? The obesity epidemic — the frequency of obesity has gone up and up and up in the United States. In 1990, if you looked at the prevalence of gout and then compared it to almost 30 years later in 2019, the prevalence of gout rose by almost 100% in males and almost 50% in females. If you look at obesity, it's tripled in the last six decades in the United States. It was 13% in the 1960s, was 23% in 1990, it was 30% in 2000, and it's reached 42.5% in 2022. This is a problem. A BMI of greater than 40 increased from less than 2% to over 9% in the same era. If you look at normal weight, the risk of gout is about 1%. If you look at a BMI of greater than 35, the risk of gout is like 7%. So again, these problems are interconnected. They're connected through behavior. They're connected by being, I think, key elements of the metabolic syndrome. I think gout should be a member of the metabolic syndrome, but they haven't called me about this yet.

We do know that obesity will increase uric acid production and decrease uric acid excretion and lead to more adipokines that are pro-inflammatory, that can lead to not just gout but gout flares. Obesity does all this through increase in purine turnover and purine synthesis — that's again why we have more uric acid. Overall, a BMI of greater than 30 has at least a two-fold increased risk of gout.

In a study of urate-lowering therapy, 633 patients taking febuxostat — if they looked at the patients who were obese, they were less likely to achieve their treat-to-target goal of less than six. The obese patients only 39%, the normal weight patients 64%. And similarly, obese and overweight patients in that trial had more gout flares.

We do know that — I think it's a 2016 ACR guideline — says that for every increase in BMI of more than 5% there's a resultant higher risk of gout flares, maybe a 60% or higher risk of gout flares. If you look at the 2020 ACR guidelines on the management of gout, number one on the list of recommendations is address education, diet, lifestyle, and comorbidities, and that includes obesity. Now all of that is just a conditional recommendation. They do admit that lowering weight has a variable effect but should lower uric acid and should be beneficial to the patient. But there isn't like great data on this, right? And kind of the same for EULAR when they've addressed this.

So what happens when people do lose weight with gout? First off, I would state that diet alone is no way to treat gout and to achieve targets — it's adjunctive. There are systematic reviews of like 20 or 25 trials that show that weight loss of between three and 30 kilograms lowers uric acid significantly by almost 3 milligrams per deciliter, and those people are less likely to have gouty attacks — 75% reduction. Sustained weight loss lowers uric acid. That we know is true, and it does so by improving insulin sensitivity and uric acid handling.

Interestingly, the diabetic drugs Jardiance, Farxiga, and Invokana — the SGLT2 inhibitors that are being used in diabetes and renal disease and heart failure — have uricosuric effects that lower uric acid, result in modest weight loss, and also lower
cardiovascular risk. Of all the diabetic drugs, the SGLT2 drugs are the most beneficial in gout, much more so than GLP-1s. GLP-1s, interestingly, while they're so fabulous in so many rheumatic disorders, they are good in gout, but have a modest effect or an inconsistent effect on uric acid, and in fact have been shown to not reduce the number of gout attacks and flares. That's GLP-1s.

The other strange tidbit here is that other measures to produce weight loss, when especially effective giving rapid, dramatic weight loss — like from bariatric surgery or strict ketogenic diets like Atkins — these lead to more gout flares, because one, they don't affect uric acid. They cause uric acid fluctuations because of the induced ketosis and tissue catabolism that's so rapid, leading to this transient hyperuricemia and uric acid fluctuations resulting in attacks. You don't get more attacks with GLP-1s, ever.

So my practical guidelines are that urate-lowering therapy is important in gout, but so should be obesity management, and that they should occur contemporaneously, because starting on one doesn't mean you should avoid the other. That SGLT2 inhibitors are preferred in diabetes management and for weight loss and for gout management as well. I think you should pitch the fact that weight loss has both short-term benefits — less flares — and long-term benefits with better outcomes. That's been shown, I think, repeatedly.

So obesity and gout are strange metabolic bedfellows. Treating one well requires anticipating its effect on the other, especially now that our weight loss tools are more powerful and faster acting. Again, this is the goal that we want to have with our patients — not just control of their gout, but control of their weight.