Dataset Information

LLF580, an FGF21 Analog, Reduces Triglycerides and Hepatic Fat in Obese Adults With Modest Hypertriglyceridemia.

ABSTRACT:

Purpose

To evaluate the safety and potential efficacy of LLF580, a genetically engineered variant of human fibroblast growth factor-21, for triglyceride lowering, weight loss, and hepatic fat reduction.

Methods

A multicenter, double-blind, parallel design trial in obese, mildly hypertriglyceridemic adults randomized (1:1) to LLF580 300 mg or placebo subcutaneously every 4 weeks for 3 doses.

Results

Of 64 randomized study participants, 61 (mean ± SD: age 45 ± 11 years, 49% male, 80/15/5% Caucasian/African American/other, body mass index 36.1 ± 3.8 kg/m2) received LLF580 (n = 30) or placebo (n = 31) at 7 research sites in the United States. LLF580 lowered serum triglycerides by 54% (least square mean placebo adjusted change from baseline), total cholesterol 7%, low-density lipoprotein cholesterol 12%, and increased high-density lipoprotein cholesterol 36% compared with placebo (all P < 0.001) over 12 weeks. Substantial reduction of liver fat of 52% over placebo (P < 0.001) was also demonstrated in the setting of improved liver function tests including alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, the composite enhanced liver fibrosis score, and N-terminal type III collagen propeptide (all P < 0.05). Insulin and C-peptide levels and insulin resistance by homeostatic model assessment for insulin resistance were all lower, and adiponectin higher with LLF580 treatment compared with placebo, whereas fasting glucose and glycated hemoglobin were unchanged. Reductions in biomarkers of bone formation without differences in markers of bone resorption were observed. LLF580 was generally safe and well tolerated, except for higher incidence of generally mild to moderate gastrointestinal adverse effects.

Conclusions

In obese, mildly hypertriglyceridemic adults, LLF580 was generally safe and demonstrated beneficial effects on serum lipids, liver fat, and biomarkers of liver injury, suggesting it may be effective for treatment of select metabolic disorders including hypertriglyceridemia and nonalcoholic fatty liver disease. Assessments of longer term safety and efficacy are warranted.

Clinicaltrials.gov identifier

NCT03466203.

SUBMITTER: Rader DJ

PROVIDER: S-EPMC8914500 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

LLF580, an FGF21 Analog, Reduces Triglycerides and Hepatic Fat in Obese Adults With Modest Hypertriglyceridemia.

Rader Daniel J DJ Maratos-Flier Eleftheria E Nguyen Amanda A Hom Doug D Ferriere Michael M Li Yifang Y Kompa Jill J Martic Miljen M Hinder Markus M Basson Craig T CT Yowe David D Diener John J Goldfine Allison B AB

The Journal of clinical endocrinology and metabolism 20220101 1

<h4>Purpose</h4>To evaluate the safety and potential efficacy of LLF580, a genetically engineered variant of human fibroblast growth factor-21, for triglyceride lowering, weight loss, and hepatic fat reduction.<h4>Methods</h4>A multicenter, double-blind, parallel design trial in obese, mildly hypertriglyceridemic adults randomized (1:1) to LLF580 300 mg or placebo subcutaneously every 4 weeks for 3 doses.<h4>Results</h4>Of 64 randomized study participants, 61 (mean ± SD: age 45 ± 11 years, 49% m ...[more]

PMID: 34431493

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Dataset Information

LLF580, an FGF21 Analog, Reduces Triglycerides and Hepatic Fat in Obese Adults With Modest Hypertriglyceridemia.

Purpose

Methods

Results

Conclusions

Clinicaltrials.gov identifier

Publications

LLF580, an FGF21 Analog, Reduces Triglycerides and Hepatic Fat in Obese Adults With Modest Hypertriglyceridemia.

Similar Datasets

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