We read the article of Foss-Freitas et al. (1) with great interest. Familial partial lipodystrophy (FPLD) is a rare genetic disease with no cure. Only metreleptin has been approved for treatment by the European Medicines Agency and in Japan (2). Glucagon-like peptide 1 receptor agonists (GLP-1RA) effectively treat type 2 diabetes and obesity. There were only three case reports showing their efficacy on significant glucose reduction in FPLD (1,3). This is the first and largest data set showing that GLP-1RA is a safe and effective treatment for individuals with FPLD.
In the study, the authors included a total of 14 individuals with FPLD, of which 13 had subtype FPLD1 and 1 had subtype FPLD2. After 6 months of GLP-1RA treatment, all achieved good results. Previous studies using GLP-1RA to treat people with FPLD also involved type 1 or type 2 diabetes. This study has drawn our attention because we recently discovered the first case of FPLD6 in China. The individual had been treated with dulaglutide, NovoRapid, and insulin glargine (Lantus) as well as oral hypoglycemic agents, including metformin, pioglitazone, sitagliptin (Januvia), and linagliptin, and lipid-lowering treatments, including fenofibrate and orlistat. After 1 month of treatment, a follow-up examination showed that the patient’s glycosylated hemoglobin (HbA1c) and blood glucose levels both decreased, with triglycerides showing a particularly noticeable drop. However, there was no significant change in weight and BMI, possibly because the patient was already quite lean (height 1.6 m, weight 50 kg) (4). Although other medications were used in combination, the therapeutic effect of GLP-1RA on this person with FLPD6, which is consistent with the research findings of Foss-Freitas et al., could not be ignored. To date, six subtypes and another four unclassified variants of FPLD have been described (2). The gene mutations for each disease are different, so whether GLP-1RA is effective for other types still requires more evidence.
We have some opinions on this study. The control group consisted of people with diabetes who were treated with GLP-1RA, a rigorous setup, since most individuals with FPLD have diabetes. However, the control group’s GLP-1RA results are confused; only HbA1c decreased, with no improvement in other metabolic markers. Previous studies show GLP-1RA not only reduces HbA1c but also lowers blood glucose, controls weight and BMI, and improves blood lipids (5).
FPLD involves variable body fat loss and distribution along with metabolic issues. The study found the treatment group had reduced weight, HbA1c, fasting glucose, and triglycerides, showing GLP-1RA is effective for FPLD. However, fat redistribution was not assessed. Future studies could measure anthropometry or fat thickness using image examination (2). Despite unchanged liver function, imaging should check for fat reduction. These results could better evaluate treatment.
Overall, this study provides new evidence and options for the treatment of FPLD, but data are limited due to its rarity. More follow-up and examination of new cases could add value to FPLD treatment.
Article Information
Duality of Interest. No potential conflicts of interest relevant to this article were reported.
Handling Editors. The journal editor responsible for overseeing the review of the manuscript was Steven E. Kahn.
