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Pegbelfermin improves lipid profile in type 2 diabetes with obesity
Treatment with pegbelfermin for 12 weeks improved lipid profile in adults with obesity, type 2 diabetes and a predisposition for nonalcoholic fatty liver disease, or NAFLD, according to findings from a phase 2 study published in Obesity.
Brent A. Neuschwander-Tetri, MD, a professor of internal medicine, division of gastroenterology and hepatology at the Saint Louis University School of Medicine in St. Louis, and colleagues conducted the study with a randomized, double-blind, placebo-controlled design across 12 weeks. Pegbelfermin (Bristol-Myers Squibb), which is a polyethylene glycol-modified recombinant human fibroblast growth factor 21 analogue, was assessed for how well it is tolerated and how it affected HbA1c, lipids, adiponectin and biomarkers for liver fibrosis, NAFLD and nonalcoholic steatohepatitis (NASH).
Researchers analyzed data from 120 adults with obesity and type 2 diabetes from 15 sites in the U.S. and Canada, enrolled between July 2014 and September 2015.
Researchers randomly assigned participants to one of five groups based on the size of dosage of pegbelfermin: 1 mg daily (n = 24; 46% women; mean age, 55 years); 5 mg daily (n = 24; 54% women; mean age, 55 years); 20 mg daily (n = 24; 37% women; mean age, 56 years); 20 mg weekly (n = 24; 50% women; mean age, 55 years) and placebo (n = 24; 42% women; mean age, 58 years).
After 12 weeks of treatment, there was no difference in HbA1c levels across the cohort, regardless of dosage of pegbelfermin. There were no between-group differences for body weight, fasting plasma insulin, C-peptide or insulin sensitivity. However, the researchers noted that the 20 mg weekly group experienced a mean decrease in fasting plasma glucose (P = .028) vs. placebo, whereas researchers observed an increase in whole-body insulin sensitivity in the 20 mg per day group vs. placebo group based on the Matsuda index (P = .033). The 20 mg per day group also exhibited improved levels of HDL cholesterol (P = .015) and triglycerides (P = .037).
“The improvements in HDL and triglycerides observed in the 20 mg/d treatment group are consistent with findings from clinical trials of other [fibroblast growth factor 21] analogs,” the researchers wrote. “These findings, if confirmed in subsequent studies, could be of clinical significance, as a lipid-lowering agent could reduce the overall cardiovascular risk of patients with obesity and [type 2 diabetes].”
The researchers also noted that adiponectin levels increased in the 1 mg per day (P = .043), 5 mg per day (P = .011), 20 mg per day (P = .002) and 20 mg per week (P = .034) groups vs. placebo.
Additionally, reports of adverse events were relatively stable throughout the treatment groups and the placebo group. The researchers noted that injection-site bruising, other injection-site reactions and diarrhea were the most commonly reported adverse events.
“These results suggest that pegbelfermin is generally safe, well-tolerated and associated with improvement in liver-related biomarkers and multiple metabolic parameters in patients with obesity and [type 2 diabetes] who have a high prevalence of fatty liver and who are at risk for developing NASH,” the researchers wrote. – by Phil Neuffer
Disclosures: Bristol-Myers Squibb funded this study. Neuschwander-Tetri reports he received personal fees from Bristol-Myers Squibb, Cymabay, Enanta, Gilead, Intercept, Lexicon, Madrigal and NGM Bio. Please see the study for all other authors’ relevant financial disclosures.