Diabesity is increasing demand for pens and autoinjectors worldwide
Ian Thompson takes us through the recent history of diabetes and obesity therapeutics, the innovative peptide hormone molecules that have reached the market over the 10-20 years and the equally innovative devices developed to deliver them. Ypsomed is ideally positioned as a leading pen and autoinjector developer with a growing manufacturing footprint to serve the needs of pharma customers globally.
The emergence of «diabesity»
For people of all ages, the risk of type 2 diabetes (T2D) rises with increasing body weight and the prevalence of both obesity and T2D has increased continuously in rich and developing countries since the 1980s. No more so than in USA where 35% of the population is obese, while rates in Europe range between 10-25% depending on the country. Today, the global number of people with T2D is ~500 million and with obesity is ~1’000 million. While around 50 million people or 10% of T2D are insulin dependent, and peak diagnosis of T2D is established at around 50 years of age, there is a 15-30% overlap between the T2D and obesity populations depending on the country. This means that there are many obese people that will potentially develop insulin dependency as they grow older. Considering these numbers there is a huge opportunity to treat obesity and thereby significantly reduce further growth in the number of people developing T2D as well as other life-threatening conditions.
Obesity is now recognised as a disease that increases the likelihood of comorbidities such as heart disease, hyperlipidaemia, hypertension, dementia, cancer and liver disease as well as T2D. The overall costs to healthcare systems of treating these conditions is significant and there is a huge potential to reduce healthcare costs by reducing overall levels of obesity and T2D. The term «diabesity» is used to describe the combined adverse health effects of obesity and T2D / diabetes mellitus, and was coined by Sims et al. to describe the very strong pathophysiological link between diabetes and excess body weight in 1970s. Visceral adiposity, which leads to insulin resistance, is the putative mechanism in the development of diabesity leading to insulin dependent T2D.
How can the treatment of obesity help reduce the number of people developing Type 2 diabetes and other life-threatening conditions?
The rise of the GLP-1 receptor agonists / incretin mimetics for treating T2D and now obesity
Along with newer oral drugs for treating T2D such as the DPP-IV inhibitors and SGLT-2s, the GLP-1 (glucagon-like peptide) drug class is being prescribed to combat T2D and to slow patient progression towards insulin dependency. The commercialisation of GLP-1 receptor agonists or incretin mimetics that enhance the response of the GLP-1 receptor began nearly 20 years ago with the launch of twice daily injections in 2005 of exenatide/Byetta and daily injections in 2010 liraglutide/Victoza. The weekly formulations were launched around 10 years ago, but it was the launch of liquid-stable weekly formulations, such as dulaglutide/Trulicity in 2014, semaglutide/Ozempic in 2017 and tirzepatide/Mounjaro in 2022 that is transforming the treatment of T2D.
The GLP-1 journey did not stop at treating T2D alone but has moved on to treating obesity typically using higher dosing. Following the approval of daily injected liraglutide/Saxenda in 2014 for treating obesity in selected patient populations, the two leading GLP-1s semaglutide/Wegovy in 2021 and tirzepatide/Zepbound in 2023 are now set to transform the treatment of obesity. Today there are around 15 million T2D and obese patients already being treated with GLP-1s and this is likely to increase to more than 60 million patients within 10 years. This number is therefore greater than the current patient population of around 50 million insulin dependent T2D.
Insulin-type pens for peptide hormone therapies
The development of pens for self-injection, which are essentially “cartridge-based” variable dosing, multi-dosing syringes, coincided with the development of peptide hormones and their frequent daily injections, namely insulin, hGH (human growth hormone), FSH (follicle-stimulating hormone) PTH (parathyroid hormone) and ultimately GLP-1. Reusable pens introduced in the 1980s evolved to more convenient prefilled pens in the 2000s with most pen demand today serving diabetics: T1D (Type 1 diabetes) and T2D as well as the growing demand for GLP-1 based injectable drugs. Today over 12 million reusable pens and over 1.7 billion prefilled pens are sold annually with the majority still sold to serve insulin. GLP-1s are now responsible for the additional growth in demand for pens.
All peptide hormones have a low molecular weight between 3-30 kDaltons and are generally preserved formulations for use in multidose pens. Based on daily injections the shelf-life of most peptide hormones like insulin and hGH is up to 28 days. With the development of long-acting peptide hormones which are injected on a weekly basis like GLP-1, hGH and, soon to be joined by insulin, the shelf-life of some of these drugs has been extended to up to 56 days. The fact that some GLP-1s like semaglutide can be formulated in a preserved way means that pens are an option for the GLP-1 family of drugs.
Insulin-type pens improve peptide hormone therapy administration andeffectiveness and are suitable for a broad range of injection regimens for daily and weekly dosing.
2-step autoinjectors for antibody therapies and GLP-1s
Autoinjectors, as their name implies, automatically insert the needle, and perform the injection. They are typically spring driven and usually designed for use with staked needle prefilled syringes. Ideally the drug is liquid-stable, and the full dose is injected. The need to inject a partial dose using a prefilled syringe is not very common. If different doses are needed, then providing syringes with different fill volumes or concentration is preferred. Autoinjectors were introduced in the 1970s for military and emergency use, and reusable autoinjectors were introduced for frequently injected peptide-based interferons for treating MS (multiple sclerosis) in the 1990s.
It was with the introduction of weekly and biweekly antibody-based therapies such as the TNF-inhibitors (tumor necrosis factor) for treating RA (rheumatoid arthritis) in 2006 for adalimumab/Humira and etanercept/Enbrel that the market for prefilled autoinjectors was born. Today’s 2-step manual needle insertion autoinjectors were subsequently launched 10 years later in 2016. They are buttonless, smaller and less complex than 1st generation autoinjector devices. Today there are over 70 different drugs available in prefilled autoinjectors on the market totalling over 450 million units annually. Over the last 7 years more than 30 new devices have been launched and almost all are 2-step push-on-skin devices. The largest proportion of the marketed autoinjectors are already being sold for a handful of GLP-1 therapies dominated and controlled by the two market leaders Novo Nordisk and Eli Lilly.
Significant demand for easy-to-use pens and autoinjectors
As previously discussed, some of the new GLP-1 injected drugs like semaglutide/Ozempic/Wegovy, which are simple peptides, can be formulated to be administered from a pen or from an autoinjector, while others like dulaglutide/Trulicity, which consists of GLP-1 covalently linked to the Fc region (fragment crystallizable region) of human IgG4 (immunoglobulin G4), are not available in a preserved formulation suitable for a pen. It is worth noting that mAb (monoclonal antibody) therapies as typically used for the treatment of autoimmune diseases can only be formulated for single use from an autoinjector.
Future growth of the pen and autoinjector market is largely dependent on the relative success of current and next generation GLP-1 drugs. Even though autoinjectors are more convenient for weekly injections, far fewer pen injectors are needed annually per patient. For example, based on a pen containing 4 weekly injections, a patient would only require 13 pens annually compared to 52 autoinjectors. For every 10 million patients this equates to 130 million pens vs. 520 million autoinjectors annually!
Continued development of incretins and other peptide hormones: dual and triple agonists
The dynamic market for GLP-1s for treating T2D and obesity is growing exponentially and will be even more exciting in future as there are ever more molecules in development from a broad range of pharmaceutical companies. GLP-1 belongs to the incretins which are a group of metabolic hormones that stimulate a decrease in blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood-glucose-dependent mechanism. The main incretins are GLP-1 and GIP (gastric inhibitory polypeptide) which are the active targets of some of the new dual agonists such as tirzepatide/Mounjaro/Zepbound. Other peptide hormone targets that are in development as part of dual and triple agonist molecules include glucagon, IAPP (amylin or islet amyloid polypeptide) and calcitonin.
Novo Nordisk and Eli Lilly clearly have a dominant position and economy of scale for drugs to treat T2D and obesity. New dual and triple incretin agonists are in the pipeline of both companies as well as other companies looking to enter the market. Daily oral drugs will enter the market to join Novo’s Rybelsus in a few years including new oral gliprons with approvals likely from 2027. The new glipron class is a non-peptide GLP-1 receptor agonist which is easier to manufacture than GLP-1 agonists on the market and is expected to be cheaper. How these orals will impact the use of injectables is unclear.
Ypsomed perfectly positioned with the broadest portfolio of self-injection platform products
Ypsomed’s comprehensive pen and autoinjector platform portfolio, including UnoPen and YpsoMate, is ideally positioned to support the burgeoning demand for peptide hormones for treating T2D and obesity. Ypsomed is building its global manufacturing footprint in Switzerland, Germany and China and manufacturing options in USA are currently being assessed. In addition, Ypsomed has ongoing development projects with a range of companies active in the peptide hormone space and is developing next generation devices to better serve the needs of T2D and obesity patients.
Ypsomed's manufacturing footprint for UnoPen and YpsoMate supports global growth for new treatments for T2D and obesity.
Ian Thompson
Ian Thompson has been with Ypsomed, formerly Disetronic, since 1995 in a number of roles in key account management and business development, working with pharma companies to develop and bring innovative self injection systems to market. He studied biochemistry and biotechnology in the UK, working initially in commercial roles in fermentation technology. He has worked in medical device companies since moving to Switzerland in 1990. Since 2003, Mr Thompson’s main focus has been business development and new product innovation leading to the successful development and launch of a range of new pen injector, autoinjector and patch injector customisable platform products for Ypsomed Delivery Systems.
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