We read with interest the comment from Zhou and Zhai (1) on our article in Diabetes Care documenting the efficacy and safety of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in a group of patients with various forms of familial partial lipodystrophy (FPLD) (2). Our publication builds upon earlier reports by exploring effects of GLP-1 RA on both glycemia and weight loss in this patient population. Our report included experiences from mostly the earlier members of this class, focusing not only on their weight loss but also their diabetes. Regardless of the agent, we noted clinical efficacy with evidence for weight loss and improvement in glucose control.
Zhou and Zhai noted clinical improvements in an individual from China with FPLD type 6 (caused by mutations in the LIPE gene) using 1-month-long GLP-1 RA treatment (3). Although we are intrigued by the brief details provided by the authors, it would be helpful to include the details of the mutation and more information about the clinical case. Longitudinal treatment is of significant interest and likely to be more informative clinically. This form of lipodystrophy has been reported to be associated with lipomatosis in the trunk and with lipodystrophy of the lower extremities (4,5). We agree with the comment that the clinical impact in different and novel forms of FPLD would be of interest to lipodystrophy and metabolism researchers at large. Moreover, prospective and systematic data collection would be beneficial.
Zhou and Zhai also comment on our findings in the control group. Although there was a trend toward improvements in triglyceride levels, these levels did not reach statistical significance in the FPLD population. In our article, we also compared the effects in an age- and gender-matched control group with individuals with type 2 diabetes and noted changes in HbA1c but no changes in triglyceride levels. We did not dwell too much on the latter findings, as the number of individuals in this group was likely too small to draw meaningful conclusions (compared with prior published data examining efficacy for GLP-1 RA in type 2 diabetes). However, we believe our design did lead to a control group that was adequately matched to our FPLD cohort. If more control groups with type 2 diabetes were to be examined, we believe we could also replicate the known improvements in triglycerides and liver enzymes.
Since our study was a retrospective evaluation, it lacked body composition studies and specific liver imaging. Still, we agree with Zhou and Zhai that more detailed studies are, in fact, needed to document the mechanisms of improvement more precisely. Other notable pieces of data that are absent are the assessment of insulin secretion and systemic, liver, and adipose tissue inflammation as well as data on food intake. We aim to fill these gaps in knowledge by conducting a prospective trial evaluating all these missing points with more potent GLP-1 RA treatments.
Article Information
Duality of Interest. No potential conflicts of interest relevant to this article were reported.
Handling Editors. The journal editors responsible for overseeing the review of the manuscript were John B. Buse and Vanita R. Aroda.
