Could Sodium-Glucose Co-Transporter-2 Inhibitors and Glucagon-like Peptide-1 Receptor Agonists Play a Role in Gout Treatment?
This review paper examines whether two major antihyperglycemic drug classes — sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) — may have a therapeutic role in gout management, particularly in patients who also have type 2 diabetes mellitus (T2DM). The authors describe gout as the most common form of inflammatory arthritis, driven by hyperuricemia that leads to monosodium urate crystal deposition in joints and tissues. The review summarizes evidence from multiple clinical studies suggesting that SGLT2 inhibitors lower serum urate (SU) levels, likely by promoting urinary uric acid excretion, which could benefit gout patients with comorbid T2DM. The paper also notes that SGLT2 inhibitors have demonstrated reductions in cardiovascular and renal events. By contrast, the effect of GLP-1 RAs on SU levels and urinary uric acid excretion in humans is described as unclear. The authors review mechanisms of action, structure-activity relationships, uricosuric effects, pharmacokinetic profiles, and adverse effects for both drug classes. Key limitations include the review design, reliance on studies conducted primarily in T2DM populations, and the absence of dedicated gout-specific clinical trials for either drug class.
Why this grade: This is a narrative review synthesizing existing clinical and preclinical literature rather than generating new primary human data, so it is graded as a review-level evidence source.
Gout, a metabolic and autoinflammatory disease, is the most common form of inflammatory arthritis worldwide. Hyperuricemia may result in monosodium urate (MSU) crystals forming and depositing in joints and surrounding tissues, triggering an autoinflammatory response. Effective urate-lowering therapies, as well as anti-inflammatory medications, are used to treat gout. Over the past few decades, new antihyperglycemic drug classes with different modes of action have been added to treat hyperglycemia in type 2 diabetes mellitus (T2DM). Two of these drug classes, sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), have reduced cardiovascular and renal events and mortality. Several clinical studies have demonstrated that SGLT2 inhibitors possess urate-lowering properties, which may be beneficial for treating gout patients, particularly those with comorbid T2DM. Regarding SGLT2 inhibitors, some researchers have suggested that their benefits are partly explained by their ability to reduce serum urate (SU) levels, probably through increased urinary uric acid excretion. The effect of GLP-1 RA on SU levels and urinary excretion of uric acid in humans is unclear. This paper reviews the mechanisms of action of SGLT2 inhibitors and GLP-1RA, both approved and in development. Additionally, it examines what is known about their structure-activity relationships, uricosuric effects, pharmacokinetic profiles, and adverse effects.
Educational summary of published research — not medical advice. License: cc by. Full text is shown only where licensing permits.