Efficacy and Safety of SGLT2 Inhibitors in Patients With Genetic Lipodystrophy: A Real-Life Experience From a National Reference Network.

Abstract

Aim: Lipodystrophy syndromes are rare diseases with metabolic and cardiovascular consequences. This study explores the metabolic and renal effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with genetic lipodystrophy.

Patients and methods: Patients with familial partial lipodystrophy (n = 57) or congenital generalised lipodystrophy (n = 2) (86% women) were initiated with SGLT2i in the French reference network PRISIS. We retrospectively collected clinical and biological data before initiation, after 6-18 months (short-term, mean ± SD 12.5 ± 6.4 months) and at the latest follow-up on SGLT2i (long-term, 29.0 ± 10.7 months).

Results: Body mass index decreased from 25 [22.9-28] (median [IQR]) to 24.4 [22.1-26.5] then 23.9 [22.1-26.4] kg/m² (p < 0.001) and HbA1c from 7.8 [7.1-8.8] to 7.3 [6.7-7.7] and 7.3% [6.9-8] (p < 0.01 and p = 0.05, respectively). Systolic blood pressure (130 [120-143.25] to 126 [120-137] mmHg), ALT (33 [23.5-44] to 30 [26-40] IU/L), GGT (44 [28.5-62.5] to 37 [27.85-45.5] IU/L) and liver stiffness (6.8 [5.9-11.8] to 5.8 [5-6.9] kPa) declined significantly at short-term (p < 0.05, 0.02, 0.02 and < 0.01, respectively). The dual-energy X-ray absorptiometry-based fat mass percentage (23.6 [18-29.3] to 20.8 [17.8-25.3], p = 0.07) and truncal-to-lower limb fat ratio (1.36 [1.18-1.50] to 1.17 [0.98-1.41], p = 0.08) tended to decrease at short-term. Urinary albumin-to-creatinine ratio, when elevated at baseline (> 3 mg/mmol, n = 18 patients), decreased from 10.8 [6.3-24.9] to 8.0 mg/mmol [2.8-14.4] (p = 0.02). Treatment discontinuation (7%) was mainly due to vaginal mycoses. No serious adverse events were reported.

Conclusion: In a real-life setting, SGLT2i therapy is associated with improvement in HbA1c, body weight, blood pressure, hepatic parameters and albuminuria in patients with genetic lipodystrophy.