Novel Super Long-Acting Insulin, GLP-1 Receptor Agonist Show Promise in Diabetes

Adopting a 'Cascade of Care' Approach to Diabetes
Adopting a ‘Cascade of Care’ Approach to Diabetes
PE0139, a super long-acting basal insulin, and PB1023, a weekly GLP-1 receptor agonist, may lead to novel approach to treating diabetes.

BOSTON — Two new therapies — the super long-acting basal insulin PE0139 and the weekly glucagon-like peptide-1 (GLP-1) receptor agonist PB1023 — may lead to a novel approach for treating diabetes, according to data presented at the American Diabetes Association (ADA) 75th Scientific Sessions.

Both PE0139 and PB1023 are based on ELP biopolymer technology in which an inert repeating polymeric elastin-like peptide (ELP), which is expressed in Escherichia coli (E. coli), is fused to the protein of interest, such as insulin and GLP-1, respectively.

“Both products … are fully stable in a simple liquid formulation. On injection subcutaneously, they go through a heat-induced phase transition which leads to an effective depot being formed under the skin, and the product is then slowly released into the circulation and then slowly cleared from the circulation, so we get prolonged exposure through two distinct mechanisms,” Jim Ballance, PhD, an employee of PhaseBio Pharmaceuticals, which is developing PE0139 and PB1023, told Endocrinology Advisor.

PE0139 First-in-Man Clinical Trial

At this year’s meeting, Poul Strange, MD, PhD, also an employee of PhaseBio Pharmaceuticals, presented data from a first-in-man dose escalation trial evaluating PE0139 in patients with type 2 diabetes.

HbA1c ranged from 6.0% to 10.0% and patients were taking a stable dose of basal insulin and at least one oral antihyperglycemic agent for 3 months before study entry. Insulin was withheld for 7 days before and 7 days after dose.

Results indicated that PE0139 demonstrated dose-related increases in mean serum concentrations and mean decreases in fasting plasma glucose (FPG) with PE0139 vs. placebo (–2 mg/dL to –34 mg/dL; P=.06). PE0139 also resulted in consistently lower free fatty acid levels vs. placebo, measured 7 days after dosing.

The researchers found no dose-limiting toxicities, as well as no severe adverse events or hypoglycemia. In more than 5% of patients, treatment-related adverse events included mild injection site erythema (8%).

“Results from the trial demonstrated that the pharmacokinetic properties of our new insulin will make it well suited for an injection once a week for patients, provided further development,” Strange told Endocrinology Advisor.

“The drug candidate was safe and well tolerated, and we were able to demonstrate the effect that we like to see with an insulin for these patients.”

Combining PB1023 and PE0139

In a second study presented by Ballance, researchers evaluated the potential combination of the super long-acting insulin PE0139 with the once weekly GLP-1 receptor agonist PB1023.

Ballance and colleagues administered the subcutaneous injection PE0139, PB1023 and a co-formulation to db/db mice and analyzed the effect on FPG and an intraperitoneal glucose tolerance test.

The researchers noted normalized FPG and glucose tolerance when sub-therapeutic doses of the individual components were administered in co-formulation.

In addition, administration of a co-formulation of PE0139 and a rapid-acting insulin-ELP to STZ-treated mice resulted in a rapid but sustained reduction in FPG. Pharmacokinetic analysis also showed that sustained and rapid release ELP fusion proteins are independently released into the circulation

“The field in terms of GLP-1 receptor agonists is moving toward less frequent injections. There are now three weekly GLP-1 receptor agonists on the market but no weekly insulins to be combined with it. We have shown in animal models a synergistic effect when we combine the two,” Ballance said.


  1. Marquez F et al. Abstract 100-OR: PE0139, the First Recombinant Fully Human Monomeric Super-Long-Acting Basal Insulin to Display a Sustained Nearly Peakless Insulin Profile following a Single Subcutaneous Dose in Subjects with T2DM Supporting Weekly Dosing.
  2. Arnold S et al. Abstract 168-OR: Synergistic Action of PE0139, a Super-Long-Acting Basal Insulin, and PB1023 a Weekly GLP-1 Receptor Agonist. Both presented at: American Diabetes Association (ADA) 75th Scientific Sessions; June 5-9, 2015; Boston.