Oral Leptin Formulation Offers Short-Term Benefit for Type 1 Diabetes Patients

Investigative ORMD-0701 has potential to regulate the insulin-glucagon balance in patients.

New findings from the 2021 American Diabetes Association (ADA) Virtual Meeting support the potential and safety of ORMD-0701, a novel oral human leptin formulation, in patients with type 1 diabetes.

“Recent understandings of the role of leptin in glucagon and glucose homeostasis, have flagged it as a target for management of type 1 diabetes,” wrote the investigative team, spearheaded by Miriam Kidron, PhD, of Oramed Pharmaceuticals.

“While historically thought to be involved in long-term regulation of appetite and energy expenditure, leptin is now known to regulate food absorption, mucus secretion, intestinal motility and inflammatory processes,” they continued.

They further indicated that initial mouse model studies have shown that leptin can directly inhibit glucose uptake as well as regulate glucagon levels and insulin requirements.

Studies also show that leptin can improve hyperglycemia in mouse models with type 1 diabetes and reduce the need for insulin in insulin-resistant diabetic patients; however, leptin-based medications are only available as injectables.

While oral protein-based drugs are poorly absorbable, ORMD-0701 was designed with a potent absorption enhancer that promotes absorption of the active ingredient across the intestinal epithelium. The drug also has a species-specific protease inhibitor that offers protection for the active ingredient, thus preventing mechanical and enzymatic degradation.

A First-in-Human Study

Kidron and colleagues conducted a first-in-human, placebo-controlled trial to assess the safety and short-term effects of a single 3 mg dose of ORMD-0701 in fasting patients with type 1 diabetes.

They enrolled a total of 10 patients, 7 of whom were assigned to receive single dose ORMD.

Patient ages ranged from 18-50 year, and all were treated with an insulin pump. Further, glucose levels were between 100 mg and 280 mg. No patient received any other hypoglycemia treatment.

At study outset, basal insulin pump rates were lowered to 50% of their regular program, and the investigators monitored glucose and glucagon for 3 hours post-administration.

“Glucagon area under the curve 30-120-min post-treatment (AUC30-120) was 0.60 ng*min/L lower than baseline values, while it rose by 0.69 ng*min/L in the placebo group,” they reported. 

“Similar trends were recorded for glucose AUC30-120 measures, with an 0.43 mmol*min/L decrease from baseline AUC in the active group versus a 0.24 mmol*min/L increase in the placebo group.”

However, they found that glucose and glucagon levels returned to baseline levels for all patients at the end of the 3-hour monitoring period.

The team noted there no significant changes in blood leptin levels in either treatment cohort.

“These preliminary findings set the stage for further assessment of oral leptin and its impact on normalizing the insulin-glucagon balance in patients with T1D,” they concluded.

The study, “Glucose- and Glucagon-Lowering Effect of a Single Oral Leptin Dose in Type 1 Diabetes Patients,” was presented at ADA 2021.