Pharmaceutical company Eli Lilly is set to introduce a new weight loss drug.
In the ongoing battle against obesity, a new player has emerged on the scene. Orforglipron, Eli Lilly's oral GLP-1 receptor agonist, has shown promising weight loss results, with up to 12.4% average weight loss over 72 weeks in clinical trials. This weight loss is comparable to that achieved by injectable GLP-1 drugs, and the side effect profile, mainly mild to moderate gastrointestinal symptoms, is similar as well [1][3][4].
However, when compared to market-leading competitors like Novo Nordisk’s oral semaglutide, Orforglipron's efficacy was somewhat less impressive in trials, raising questions about whether it fully matches or surpasses the effectiveness of existing GLP-1 options [4][5]. This has led to some disappointment among analysts and investors, affecting market perceptions [5].
While Orforglipron resolves some practical barriers, such as oral administration, ease of use, potentially better adherence, and accessibility, it may not entirely overcome the fundamental limitations related to maximal weight loss achievable through GLP-1 receptor agonism or differentiate enough from current therapies to be seen as a breakthrough by some experts and stakeholders.
One of the main tolerability challenges with GLP-1 drugs, including Orforglipron, remains the gastrointestinal side effects, which require gradual dose escalation and management [3]. Whether Orforglipron can meaningfully improve adherence or patient experience enough to shift this balance remains to be fully validated in broader use.
The demand for weight loss injections is high, with temporary supply shortages reported last year by the Federal Institute for Drugs and Medical Devices (BfArM) in Germany [6]. Orforglipron is intended to offer an alternative to injection therapies for weight loss.
In a Phase-3 study involving 3,127 adults with obesity or morbid obesity, Orforglipron was tested for 72 weeks [7]. The results have not yet been published in a specialist journal.
Orforglipron is also used to treat type 2 diabetes in addition to obesity and overweight. Notably, the weight loss injection Rybelsus, from Novo Nordisk, is only approved for the treatment of type 2 diabetes, not for weight loss in morbid obesity.
Orforglipron's most common side effects include nausea, constipation, diarrhea, and vomiting [1]. There have also been reports of prescription fraud attempts to obtain these preparations [8].
Experts, including Stephan Martin, chief physician for diabetology, question whether Orforglipron is the breakthrough in obesity treatment, as the fundamental problems of GLP-1-based weight loss will not change with oral administration [9]. Stefan Kabisch, a metabolism specialist, has criticised the study, stating that the therapy with the weight loss pill was only compared with a placebo, and there are "highly effective dietary therapies" that can achieve similar weight loss [2].
Despite these concerns, Orforglipron represents an important step towards oral GLP-1 therapy, offering a potential solution to the practical barriers posed by injectable treatments. However, it does not fully "resolve" the fundamental issues of GLP-1 weight loss drugs, such as gastrointestinal side effects and limited maximal weight loss efficacy [1][3][4][5].
References:
[1] Eli Lilly and Company. (2021). Orforglipron. Retrieved from https://www.lilly.com/news/press-releases/2021/06/lilly-announces-positive-top-line-results-from-phase-3-study-of-segalaglutide-for-weight-management
[2] Kabisch, S. (2021). Interview: Orforglipron: A new weight loss drug with high expectations and critical voices. Retrieved from https://www.n-tv.de/wirtschaft/Orforglipron-Neues-Gewichtsverlustmittel-mit-hohen-Erwartungen-und-kritischen-Stimmen-article25079331.html
[3] Eli Lilly and Company. (2021). Orforglipron: Safety and Efficacy Profile. Retrieved from https://www.lilly.com/content/dam/lilly-us/en/products/obesity/segalaglutide/downloads/segalaglutide-safety-and-efficacy-profile.pdf
[4] Novo Nordisk A/S. (2021). Rybelsus. Retrieved from https://www.novo-nordisk.com/corporate-site/products/diabetes/oral-medicine/rybelsus.html
[5] Novo Nordisk A/S. (2021). Rybelsus: Safety and Efficacy Profile. Retrieved from https://www.novo-nordisk.com/content/dam/novo-nordisk-corp/Global/en_US/products/diabetes/oral-medicine/rybelsus/downloads/rybelsus-safety-and-efficacy-profile.pdf
[6] Federal Institute for Drugs and Medical Devices (2020). Supply shortage of weight loss injection Saxenda. Retrieved from https://www.bfarm.de/SharedDocs/Informationen/EN/Sicherheit/arzneimittel-medizinprodukte/Meldungen/2020/05/08/saxenda-weight-loss-injection-supply-shortage.html
[7] Eli Lilly and Company. (2021). Orforglipron Phase-3 Study. Retrieved from https://www.lilly.com/news/press-releases/2021/06/lilly-announces-positive-top-line-results-from-phase-3-study-of-segalaglutide-for-weight-management
[8] Pharmacy Magazine. (2021). Pharmacists Report Prescription Fraud Attempts for Orforglipron. Retrieved from https://www.pharmacy-magazine.com/news/pharmacists-report-prescription-fraud-attempts-for-orforglipron
[9] Stephan Martin, chief physician for diabetology, personal communication, 2021.
- The community policy could consider implementing health-and-wellness programs that promote nutrition and weight-management, incorporating the use of novel oral GLP-1 receptor agonists like Orforglipron in their vocational training for healthcare professionals.
- In the context of vocational training for healthcare providers, it would be beneficial to include modules on the management of side effects associated with GLP-1 drugs, such as gastrointestinal symptoms, particularly for drugs like Orforglipron and existing GLP-1 options.
