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SGLT2 inhibition: A possible mode-of-action for inflammatory skin diseases?

Presented by
Allison Holt, UMass Chan Medical School, USA
AAD 2024
Comparing incidence rates of various inflammatory skin diseases among patients starting their type 2 diabetes treatment either on sodium-glucose cotransporter-2 (SGLT2) inhibitors or dipeptidyl peptidase-4 (DPP4) inhibitors, a population-based cohort study found a lower hazard for all skin conditions besides psoriasis in patients on SGLT2 inhibitors.

Besides their glucose-lowering and weight-lowering properties, SGLT2 inhibitors are suggested to include anti-inflammatory and immunological features associated with protective cardiorenal effects [1]. For MD candidate Allison Holt (UMass Chan Medical School, MA, USA) and colleagues, these properties of SGLT2 inhibitors together with existing data on links between inflammatory skin diseases and diabetes, induced an interest in a possible effect of SGLT2 inhibition on the occurrence of these conditions in diabetic patients.

Their population-based cohort study analysed 550,195 patients with type 2 diabetes who initiated treatment with SGLT2 inhibitors in the US between 2014 and 2024. Based on a propensity score, these were matched to the same number of patients starting DPP4 inhibitors. Besides matching for demographics and socioeconomics, the covariates included comorbidities such as cardiovascular and renal disease, laboratory data such as mean HbA1c, and knowledge about medication, smoking, and healthcare utilisation. The participants were followed up for new onsets of inflammatory skin diseases like psoriasis, seborrheic dermatitis, lichen planus, acne vulgaris, alopecia areata, and vitiligo.

The results revealed differences in the incidence of the diseases between the SGLT2 inhibitors and the DPP4 inhibitors users. Incidence rates of alopecia areata, vitiligo, acne vulgaris, and seborrheic dermatitis were decreased in the cohort on SGLT2 inhibitors with incidence rates per 1,000 person-years of 0.09, 0.09, 0.56, and 1.24 compared with 0.17, 0.15, 0.83, and 1.8 in the DPP4 inhibitors cohort.

Using a Cox proportional hazard model, the corresponding hazard ratios for the likelihood of a new onset of these conditions were calculated: alopecia areata 0.7 (95% CI 0.60–0.82), vitiligo 0.79 (95% CI 0.68–0.92), acne vulgaris 0.87 (95% CI 0.81–0.93), and seborrheic dermatitis 0.89 (95% CI 0.86–0.94). In contrast, a hazard ratio of 1.08 (95%CI 1.03–1.13) stood for a somewhat increased risk of psoriasis on SGLT2 inhibitors. “This is consistent with an earlier study,” explained Ms Holt, referring to a population-based Taiwanese investigation [1,2].

Bearing in mind that these findings stemmed from medical record data, the researchers believe that future clinical trials are warranted to evaluate the safety and efficacy of SGLT2 inhibitors in patients with type 2 diabetes and concomitant inflammatory skin disease [1].

    1. Holt A. Inflammatory skin disease following the use of SGLT2 inhibitors for diabetes mellitus. LB2, 2024 AAD Annual Meeting, 8­–12 March, San Diego, USA.
    2. Ma SH, et al. Clin Exp Dermatol. 2022;47(12):2242-2250.

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