SUN-660 Efficacy of Thiazolidinediones in the Control of Insulin Resistance in Patients with Congenital or Acquired Lipodystrophy

Abstract Disclosure: N.K. Balarezo: None. A.D. Felomeno: None. G.B. Coscarelli: None. J.D. Panzan: None. L. Pizetti: None. R.S. Ranieri: None. A. Galhardo: None. I.C. Magalhães: None. Q.M. Andrade: None. A.N. Guanaes: None. V.B. Iervolino: None. Introduction: Lipodystrophies are genetic or acquired disorders characterized by selective fat loss and a predisposition to insulin resistance. Depending on fat loss severity, patients are at higher risk for metabolic complications such as early-onset diabetes, hypertriglyceridemia, and hepatic steatosis. Insulin-resistant individuals exhibit increased endogenous insulin secretion or require high exogenous insulin doses. Thiazolidinediones (TZDs) improve glucose uptake in adipose tissue, muscle, and liver. Their potential in lipodystrophy management includes metabolic improvements and adipose tissue redistribution. However, their effects on lipid metabolism and cardiovascular risks require careful evaluation. Methods: A systematic review with meta-analysis of randomized controlled trials and clinical trials published from January 2003 to January 2025 in PubMed, Embase, and Cochrane. Studies on congenital or acquired lipodystrophy patients using TZDs for insulin resistance were included. Results: A 6-month trial with 37 patients showed that metformin and rosiglitazone similarly reduced insulin resistance, but only rosiglitazone increased subcutaneous adipose tissue (SAT). Metformin caused more gastrointestinal symptoms, while rosiglitazone lowered HbA AUC but increased fasting remnant-like particle cholesterol (RLP-C) and triglycerides. A study of 28 HIV-associated lipodystrophy patients found rosiglitazone improved insulin sensitivity and adiponectin levels while lowering free fatty acids but increasing LDL and total cholesterol. A comparative study with 31 HIV-positive patients found both metformin and rosiglitazone reduced fasting insulin and HOMA index. Metformin improved HDL and lowered total cholesterol, while rosiglitazone worsened lipid profiles. Metformin also had stronger anti-inflammatory effects, reducing MCP-1 levels. A 24-week trial with 30 HIV-positive patients showed rosiglitazone reduced fasting insulin and hepatic fat but worsened triglyceride and cholesterol levels without improving HDL. Conclusion: Both rosiglitazone and metformin improved insulin sensitivity, but their metabolic effects differed. Rosiglitazone promoted peripheral fat gain and insulin sensitivity but worsened lipid profiles. Metformin reduced visceral and subcutaneous fat, improved lipid markers, and had stronger anti-inflammatory effects but limited fat redistribution. These findings highlight the need for individualized treatment, balancing benefits and risks to optimize lipodystrophy management. Presentation: Sunday, July 13, 2025