Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely popular for managing type 2 diabetes in patients. This class of medications lowers blood glucose levels by increasing glucose-dependent insulin secretion. In addition to triggering insulin release, they inhibit production of glucagon—a hormone that induces the liver to release stored sugar into the bloodstream. Furthermore, they slow glucose absorption into the bloodstream by reducing the rate of gastric emptying and slowing the speed of nutrient absorption in the bloodstream, thus reducing appetite.
GLP-1 RAs were only available as injectable drugs until an oral tablet formulation was approved by the FDA in September 2019. Oral semaglutide, developed for oral administration for type 2 diabetes treatment, presents significant benefits to patients.
A study conducted by Novo Nordisk in collaboration with Ossian Health Economics and Communications found that semaglutide—both in injected form (1 mg) and oral form (14 mg)—was the most cost-effective GLP-1 RA in the US with regard to bringing patients to glycemic control targets.
The study compared the short-term cost effectiveness of oral and injectable semaglutide with several currently-available injectable drugs. The cost analysis was performed in terms of achieving glycemic control targets of HbA1c ≤6.5% and HbA1c <7.0%, as recommended by the American Diabetes Association (ADA) and the American Association of Clinical Endocrinologists.
Cost of control assesses the value for money for each intervention simply and transparently. In order to analyze cost of control, the annual treatment cost associated with each aforementioned GLP-1 RA was divided by the ratio of patients accomplishing target treatment. This methodology is consistent with cost of control analysis previously published in peer-reviewed literature. Payment amounts were calculated in US dollars and based on wholesale acquisition charges for 2019. The calculations for cost of control were implemented using a cost of control model, which was programmed using Microsoft Excel. Projected outcomes were limited to a 1-year time horizon; this obviated the need to discount cost and clinical outcomes.
Two treatment targets were used to determine successful control: HbA1c <6.5% and HbA1c <7.0%. Seven GLP-1 RAs were evaluated: oral semaglutide 14 mg, once-weekly dulaglutide (1.5 mg), semaglutide (1 mg), and exenatide (2mg), once-daily liraglutide (1.8 mg) and lixisenatide (20 mg), and twice-daily exenatide (10 mg).
Once-weekly (injectable) semaglutide 1mg and oral semaglutide 14 mg were found to achieve the lowest costs of control among all drugs. For achieving a target of HbA1c <6.5%, semaglutide 1mg and oral semaglutide 14 mg respectively cost $15,430 and $17,383 per patient annually. For a target of HbA1c <7.0%, the cost of control was $12,627 with once-weekly semaglutide 1mg, and $13,493 with oral semaglutide 14mg per patient per year. All other drugs cost higher amounts.
In the base case analysis, for achieving HbA1c <6.5%, lixisenatide 20 µg was associated with the highest expense for control, at $36,552 per patient. And exenatide 10 µg had the highest cost of control, at $20,695 per patient achieving target, for the endpoint of HbA1c <7.0%.
The transparency of the cost-effectiveness analysis in the present study allows replication by other research groups and ease of updates with new clinical and cost data. The study also assesses cost-effectiveness over a 1-year period, thus reducing the uncertainty associated with traditional long-term cost modeling, which projects short-term trial data over long lifetimes.
Studies have shown a general preference for oral administration of drugs over injections. Oral semaglutide thus removes a barrier to medication adherence, which can improve outcomes with the exception of cases where patients may prefer a once-weekly injection to daily oral medications. The optimal medication route and dosage differs from patient to patient and should be determined based on physician discussions and ADA recommendations.