Once I invited some friends to my house for dinner. I prepared boiled crab legs, grilled racks of lamb,

chilled asparagus, stewed tofu with mushrooms, and red bean slush for dessert. I have also stocked my

refrigerator with various types of beers. Some bottled water was also there for those who refuse to

indulge themselves. I anticipated that my friends would appreciate my warm hospitality; however, one

gentleman about 50 years old, with a slightly plump figure, shook his head with an extremely bitter

smile: “I don’t dare to consume anything that you prepared, except for the water.” I immediately

realized that this friend must have experienced a gout flare recently, whereas all the food I prepared,

including the beer, was purine-rich and will easily elevate his blood urate levels, potentially trigger

another attack. Oh, my goodness, I certainly didn’t intend to harm him!

Among thousands of human diseases, gout is one of the few possessing a super long history, with its

first identified documentation dating back as early as 2640 BC in ancient Egypt, and with a big name:

King’s disease. The name probably originated from the fact that in the past, only kings had the privilege

to consume extremely rich foods and unlimited wines. Gout fortunately accompanied many famous

people’s lives during their severe pains, including Kublai Khan, Hery VIII, Beethoven, Christopher

Columbus, and Benjamin Franklin.

If not combined with other diseases such as diabetes, hypertension, myocardial infarction, or kidney

failure, gout alone is typically not life-threatening. But as many have attested, it is truly agonizing,

excruciating, and harrowing. The pain that it brings is so piercing and crushing that the patients find it

impossible to focus on work or study, fall to asleep, eat properly, and even stand up straight or walk

gracefully. The swelling and redness in multiple joints, usually starting from the big toe, may persist for

several days to several weeks. The worst of worst, after the traces of damage are completely gone and

the patients hope to enjoy a peaceful time, a new flare can strike suddenly and ruin the lives of the

affected again.

Gout sufferers will love some recent encouraging news. It is widely known that many gout patients are

concomitantly affected with diabetes (you may get an idea by looking at the portraits of Kublai Khan and

Hery VIII). A type of medication, sodium-glucose cotransporter-2 inhibitors (SGLT2is), have been used to

treat type II diabetes since 2014. Researchers observed that SGLT2is benefit the cardiovascular and renal

systems of the diabetic patients and can lower their blood urate levels. Naturally this led to an

assumption that SGLT2is may have the potential to prevent or relieve gout. Did the researchers need to

conduct animal experiments on little white mice to test the hypothesis? Thank God, no. Instead, the

researchers meticulously analyzed tons of historical clinical data. The team led by Hyon K. Choi and

Yuqing Zhang from the Division of Rheumatology, Allergy, and Immunology at Massachusetts General

Hospital, recently investigated the General Population Database spanning from 1 January 2014 to 30

June 2022 on patients with gout and type 2 diabetes, by using Propensity score–matched and new-user

cohort study. These patients were either treated with SGLT2is or dipeptidyl peptidase 4 inhibitors s

(DPP-4is), another glucose-lowering agent which has no effect on lowering serum urate levels, at their

illness duration. The researchers discovered that patients treated with SGLT2is exhibited significantly

fewer recurrent gout flares and experienced much lower rates of myocardial infarction and stroke, as

confirmed by the records from emergency department (ED), hospitalization, outpatient visits, and

medication dispensing records. This important discovery was published in the Annals of Internal

Medicine on 25 July 2023, under the title “Comparative Effectiveness of Sodium–Glucose Cotransporter-

2 Inhibitors for Recurrent Gout Flares and Gout-Primary Emergency Department Visits and

Hospitalizations”. (https://www.acpjournals.org/doi/10.7326/M23-0724) (twitter link:

https://t.co/U00HZG1SHo).

The ink on the Ann Intern Med paper was still moist when another research group, led by Guanghua Lei

and Chao Zeng from the Xiangya Hospital, Central South University, China, published a paper in JAMA on

August 25, 2023, with the title “Gout Flares and Mortality After Sodium-Glucose Cotransporter-2

Inhibitor Treatment for Gout and Type 2 Diabetes”. Notably, the corresponding authors of the Ann

Intern Med paper also served as co-authors on the JAMA paper, demonstrating their collaboration.

(https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808753#:~:text=Findings%20In%20t

his%20cohort%20study,initiation%20of%20active%20comparator%20treatments). This study was a

population-based retrospective cohort study performed on patients with gout and type 2 diabetes for

the period of January 1, 2013 to March 31, 2022, using a UK primary care database. Researchers

discovered that among the 5931 patients with gout and type 2 diabetes, initiation of SGLT2i treatment

was associated with 19% fewer recurrent gout flares and 29% lower mortality than initiation of active

comparators including glucagonlike peptide-1 receptor agonists [GLP-1 RA] or DPP-4i. These research

findings can be viewed as a cross-confirmation on the beneficial role of SGLT2i on gout therapies, in

alignment with the Ann Intern Med paper’s conclusions.

A harsh reality is that the previous King’s disease is becoming increasingly prevalent worldwide, which

affected only 20 million adults globally in 1990, whereas the number has risen to 41 million in 2017.

Gout is no longer only rich old man’s disease, but it has also become the nightmares of young

populations under 40 years and women post menopause. While gout is not curable, it is still

manageable. When considering the safety and cost, older medications that have been already widely

used are often more attractive than novel alternatives.

Interestingly, one of the friends I invited, as I mentioned at the beginning of the story, is a young

endocrine doctor. He always complains that he spends too much time on medical record-keeping. If he

happens to have read those two research papers, he might reconsider his complaints. Some medications

or treatment strategies will survive the scrutiny of time and stand out from the historical data. So,

particularly in the medical field, it is imperative to maintain thorough records and allow time to reveal

the truth.