Therapeutic indications and metabolic effects of metreleptin in patients with lipodystrophy syndromes: Real‐life experience from a national reference network

Abstract

Aim: To describe baseline characteristics and follow-up data in patients with lipodystrophy syndromes treated with metreleptin in a national reference network, in a real-life setting.Patients and Methods: Clinical and metabolic data from patients receiving metreleptin in France were retrospectively collected, at baseline, at 1 year and at the latest follow-up during treatment.Results: Forty-seven patients with lipodystrophy including generalized lipodystrophy (GLD; n = 28) and partial lipodystrophy (PLD; n = 19) received metreleptin over the last decade. At baseline, the median (interquartile range [IQR]) patient age was 29.3 (16.6-47.6) years, body mass index was 23.8 (21.2-25.7) kg/m 2 and serum leptin was 3.2 (1.0-4.9) ng/mL, 94% of patients had diabetes (66% insulin-treated), 53% had hypertension and 87% had dyslipidaemia. Metreleptin therapy, administered for a median (IQR) of 31.7 (14.2-76.0) months, was ongoing in 77% of patients at the latest followup. In patients with GLD, glycated haemoglobin (HbA1c) and fasting triglyceride levels significantly decreased from baseline to 1 year of metreleptin treatment, from 8.4 (6.5-9.9)% [68 (48-85) mmol/mol] to 6.8 (5.6-7.4)% [51(38-57) mmol/mol], and 3.6 (1.7-8.5) mmol/L to 2.2 (1.1-3.7) mmol/L, respectively (P < 0.001), with sustained efficacy thereafter. In patients with PLD, HbA1c was not significantly modified (7.

Familial Partial Lipodystrophy: Clinical Features, Genetics and Treatment in a Greek Referral Center

“…Even more impressively, the metabolic benefit of metreleptin on glycemic control has not always been consistent among patients with FPLD. In a study by Mosbah et al [21], despite a significant reduction in TGs by approximately 25% after 12 months, no significant difference was observed in HbA1clevelsin FPLD patients, again in contrast to the results in the GL group. In a study by Simha et al [22], who compared the response to metreleptin between Dunnigan-type patients with severe vs moderate hypoleptinemia, serum triglycerides were reduced to a similar extent in both groups, but without a corresponding improvement in the HbA1c values.…”

“…Similarly, endogenous leptin levels failed to predict metreleptin responders in a study by Sekizkardes et al [9], but as mentioned above, a less favorable metabolic profile was associated with higher improvements in terms of TGs and HbA1c. In a study by Mosbah et al [21], the most beneficial effects of metreleptin on glucose homeostasis were shown in the patients with the lowest leptin levels. In general, the endogenous leptin cut-off point that can predict response to metreleptin treatment is still a matter of debate, considering the questionable sensitivity and, therefore, comparability of the commercially available leptin assays.…”

GLP-1 receptor agonist improves metabolic disease in a pre-clinical model of lipodystrophy

“…This is particularly the case given the lack of murine models accurately mimicking more frequently occurring partial lipodystrophies ( 2 , 4 ). As noted above, metreleptin is ineffective in many patients with partial lipodystrophy and so this patient group is particularly in need of new treatment options ( 1 , 5 , 41 , 42 ). One should be cautious extrapolating from our mouse SKO model of CGL2 to partial lipodystrophy.…”

Diagnostic and referral pathways in patients with rare lipodystrophy and insulin-resistance syndromes: key milestones assessed from a national reference center

“…However, patients with CGL could also be diagnosed in mid-childhood or even in adulthood. It is crucial to decrease the diagnosis delay of CGL, since patients may highly benefit from a specific orphan drug therapy with metreleptin [ 23 ]. The important delay from diagnosis to referral, as compared to the delay from first signs to diagnosis, illustrates the fact that reference networks should be promoted among caregivers in France.…”