Glucagon-like peptide-1 analogues - an efficient therapeutic option for the severe insulin resistance of lipodystrophic syndromes: two case reports

Abstract

BackgroundLipodystrophic syndromes are uncommon medical conditions which are normally associated with metabolic disorders, such as diabetes mellitus, dyslipidemia, and fatty liver disease. These complications are generally difficult to treat, particularly diabetes, due to severe insulin resistance. We present two case reports of successful treatment of diabetes with glucagon-like peptide-1 analogues in patients with clinical features of lipodystrophic syndromes.Case presentationTwo white women aged 49 and 60 years manifested marked central body fat deposition with severe lipoatrophy of their limbs and buttocks and pronounced acanthosis nigricans. They had hypertension, dyslipidemia, fatty liver disease, and poorly controlled diabetes (glycated hemoglobin 8.3% and 10.2%, respectively) despite the use of three classes of oral antidiabetic drugs taken in combination in the first case, and high doses of insulin in the second case. Four months after the addition of glucagon-like peptide-1 analogue to their previous treatment they both showed a pronounced improvement in metabolic control (glycated hemoglobin 5.6% and 6.2%, respectively). In the first case, a weight loss of nearly 30 kg was recorded.ConclusionsWe intend to demonstrate that glucagon-like peptide-1 analogues could be a valuable tool for patients with lipodystrophic disorders, probably by improving body fat distribution, with favorable results in insulin-sensitivity and glycemic control.

Case Report: Metreleptin Treatment in a Patient With a Novel Mutation for Familial Partial Lipodystrophy Type 3, Presenting With Uncontrolled Diabetes and Insulin Resistance

“…Conventional and intensified antidiabetic treatment failed to normalize glycemic control but the introduction of metreleptin resulted in a drastic improvement of glycemic control and plasma triglycerides. Research data regarding the use of glucagon-like-peptide-1 (GLP-1) agonists in patients with lipodystrophy are scarce and their effect has been described only in case reports (21,22). Contrary to our case, in these previous reports authors pointed out that these regimens resulted in improvement of glycemic control and in reduction of insulin requirements, suggesting the positive effect of GLP-1 analogues in the management of diabetes in lipodystrophy syndromes (21,22).…”

Clinical Characteristics, Phenotype of Lipodystrophy and a Genetic Analysis of Six Diabetic Japanese Women with Familial Partial Lipodystrophy in a Diabetic Outpatient Clinic

“…Therefore, we need to monitor the liver function intensively and perform a liver biopsy at an early stage to diagnose NASH as soon as possible in patients with PL. Body weight reduction is advised in such patients, and TZDs, GLP-1 receptor agonists, SGLT2 inhibitors, and leptin may be beneficial regimens for managing NASH ( 20 , 21 , 27 , 28 ). We must endeavor to prevent the development of NASH in diabetic patients with PL and NASH using these regimens.…”

Lipodystrophies—Disorders of the Fatty Tissue

“…In individual patients with FPLD insulin secretion disruption [ 49 ] or low dipeptidyl peptidase 4 (DPP4) levels were observed in addition to insulin resistance, suggesting the use of glucagon-like peptide 1 receptor agonists (GLP1) [ 50 ] to improve glycemic control and reduce the high insulin demand. However, no studies in the other forms of lipodystrophy have yet been conducted [ 51 ]. Furthermore, SGLT2 inhibitors have been used in individual families of congenital lipodystrophy [ 52 ].…”