SGLT2 Inhibitors Do Not Reduce Psoriasis Risk in T2DM: Study

Psoriasis is a chronic immune-mediated inflammatory skin disease, which is also fueled by the activation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and the interleukin (IL)-17/23 inflammatory pathway. Given the anti-inflammatory effects and the potential modulation of these pathways by SGLT2 inhibitors, it was hypothesized that SGLT2i therapy could lower the risk of psoriasis. However, there has been a lack of real-world data on this association.

SGLT2 inhibitors are common glucose-lowering drugs in T2DM, with established cardiovascular and renal protective effects. In addition to glycemic management, experimental evidence indicates that SGLT2i therapy could reduce systemic inflammation in psoriasis by regulating pivotal immune pathways, including the NLRP3 inflammasome and IL-17/23 signaling. The researchers performed a retrospective cohort study using data from the Taiwan National Health Insurance Database from 2007 to 2018.

The study population consisted of:

• 103,745 patients with T2DM treated with SGLT2 inhibitors

A control group of patients with T2DM not treated with SGLT2 inhibitors, matched in a 1:2 ratio according to:

• Age

• Sex

• Duration of diabetes

• Insulin use

• Comorbidities

The primary outcome was the development of psoriasis. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for potential confounders.

Key findings

• After adjusting for confounding variables, there was no statistically significant difference in the risk of incident psoriasis between SGLT2i users and non-users.

• The adjusted hazard ratio for psoriasis in SGLT2i users was 1.24 (95% CI 0.95-1.64), which showed no significant overall protective or harmful effect.

• However, certain clinical variables were independently linked with an increased risk of psoriasis.

• The use of insulin was significantly linked with an increased risk of psoriasis, with an HR of 1.65 (95% CI 1.24-2.19).

• Chronic liver disease and cirrhosis were also linked with an increased risk, with an HR of 1.34 (95% CI 1.01-1.77).

• The subgroup analysis revealed a significantly increased risk of psoriasis in SGLT2i users with renal disease.

• In this subgroup, the use of SGLT2i was linked with a 2.73-fold increased risk of psoriasis, with an HR of 2.73 (95% CI 1.45-5.13).

• This observation indicates a possible interaction between renal impairment and SGLT2i exposure in the modulation of psoriasis risk.

The protective role of SGLT2 inhibitors in psoriasis could not be confirmed in patients with type 2 diabetes mellitus. The risk of psoriasis was not significantly different between SGLT2 inhibitors and non-users, but SGLT2 inhibitor therapy was found to be associated with a 2.7-fold higher risk of psoriasis in patients with T2DM and underlying renal disease.

Reference:

Ma, S.-H., Wu, C.-Y., Lyu, Y.-S., Chou, Y.-J., Chang, Y.-T., & Wu, C.-Y. (2022). Association between sodium-glucose co-transporter 2 inhibitors and risk of psoriasis in patients with diabetes mellitus: a nationwide population-based cohort study. Clinical and Experimental Dermatology, 47(12), 2242–2250. https://doi.org/10.1111/ced.15385