SGLT-2 inhibitors and the prevention of autoimmune rheumatic disease Save

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have benefits beyond glycemic control, including cardioprotective and nephroprotective effects, with modest weight loss. Now a recent population study suggests that SGLT-2i may have immunomodulatory effects and the ability to preven autoimmune disease.

SGLT-2i have been shown to reduce major adverse cardiovascular events and hospital admissions for heart failure, and reduce renal progression in people with chronic kidney disease. These effects have also been seen in patients iwth pre-existing autoimmune disease.

SGLT-2i agents include canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Jardiance), bexagliflozin (Brenzavvy), and ertugliflozin (Steglatro).

A retrospective Korean population study by eet al studied the treatment of over 2 million NIDDM patients with either SGLT-2i or a sulfonylurea for a median of 9 months and demonstrated that SGLT-2i was associated with an 11% lower risk of incident autoimmune rheumatic diseases compared with sulfonylureas (hazard ratio 0.89). SGLT-2i use was associated with a significantly reduced risk of future inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis), but not systemic autoimmune rheumatic diseases (systemic lupus erythematosus, Sjögren’s disease, systemic sclerosis, idiopathic inflammatory myositis, mixed connective tissue disease, polymyalgia rheumatica, or vasculitides)).

The rate difference between groups was −6.5 diagnoses per 100 000 person years, yielding a number needed to treat of 15 385. 

This is biologically plausible as SGLT-2 inhibitors can reduce key pro-inflammatory cytokines and induce shifts in macrophages from pro-inflammatory M1 to anti-inflammatory M2 subtypes.

.Autoimmune rheumatic diseases are relatively rare diagnoses, and the number needed to treat were large.  Hence these findings will need to be studied in other populations.

While GLP-1 receptor agonists have been shown to reduce weight and yield cardiovascular and disease outcome benefits in rheumatic patients, it is unknown if GLP-1 receptor agonists are capable or preventing autoimmune rheumatic diseases.