Over 460 million people worldwide are now on lifelong diabetes medication, which has become an epidemic. How close are we to discovering a diabetes drug capable of curing this chronic illness by diabetes research and clinical practice?
Diabetes is a leading cause of heart attacks, strokes, kidney failure, and blindness. Diabetes is expected to affect 700 million people globally by 2045. As a consequence, the World Health Organisation now considers diabetes to be an epidemic.
Diabetes, although having a substantial detrimental impact on the world’s population, presently has no recognised therapy. Although most medicines help patients regulate their symptoms to some extent, diabetics continue to face a number of long-term health complications.
High blood sugar levels result from diabetes’ effects on the hormone insulin’s regulation, which is required for cell glucose absorption. Although the symptoms of the two types of diabetes are similar, they develop in different ways.
Type 1 diabetes, an autoimmune disease, destroys the beta-pancreatic cells that create insulin. Type 2 diabetes patients, on the other hand, develop insulin resistance, which reduces insulin’s ability to decrease blood sugar.
The biotech industry is attempting to develop new diabetes medicines and is looking for the cure, the proverbial “holy grail.” Let’s take a look at what’s going on in the industry and how it will change how diabetes is controlled.
Diabetes type 1 is being treated using cell therapy to replace lost cells.
Even though it is still in its early stages of development, cell therapy is one of the most promising avenues for discovering a cure for diabetes, especially type 1 diabetes. To potentially restore normal insulin production and cure patients, insulin-producing cells must be replaced.
Early attempts to transplant pancreatic cells, however, were mostly unsuccessful, owing to the immune system’s rejection and destruction of the transplanted cells. Another constraint is a paucity of donors.
As one of the most cutting-edge solutions, the Diabetes Research Institute in the United States is working on a bioengineered mini-organ in which insulin-producing cells are surrounded in a protective barrier. This small pancreas is then implanted via the omentum, a part of the abdominal lining. In 2016, the DRI announced its first successful results, revealing that the first patient in Europe treated with this method no longer requires insulin treatment. A phase I/II trial is still ongoing.
A similar device is being developed by the American company ViaCyte in collaboration with the nonprofit JDRF. The device’s safety has previously been shown in an ongoing phase I/II research. The company is currently working to improve the engraftment of insulin-producing cells.
Furthermore, ViaCyte will initiate a phase I research of an over-the-counter beta cell replacement therapy in which beta cells are reintroduced into diabetes patients to boost insulin production. This experiment will be done in conjunction with CRISPR Therapeutics, a Swiss gene-editing company.
Evotec, a German business, is pursuing a similar technique with its stem cell-based beta cell replacement therapy, which is now in the preclinical stage of development. Sanofi and Evotec had been developing the drug jointly, but since Sanofi stopped their collaboration last year, Evotec will continue to work on it alone.
Overall, big pharma is still developing its own cell therapy treatments for diabetes. For example, Novo Nordisk, one of the world’s largest diabetes treatment firms, is developing a stem cell and encapsulating technology, and the first in-human clinical trial is now underway.
Despite the high promises, these technologies are still a long way from commercialization. Clinical trials must first establish their effectiveness. Furthermore, the cost might be expensive, considering that cell therapies for other purposes, such as cancer, have six-figure price tags and are difficult to get coverage from health insurance companies. Certain countries’ health insurance might be unwilling to finance the medication since, unlike cancer, diabetes does not usually represent an imminent threat to life.
Using Immunotherapy To Combat The Source
In type 1 diabetes, the immune system eventually damages insulin-producing cells. If the process is halted early enough, the cells may be saved and a therapy may be available.
Imcyse, a Belgian firm, is undertaking a phase I/II clinical investigation to treat type 1 diabetes using an immunotherapy that targets and destroys the immune cells responsible for pancreatic damage. A phase I trial discovered some therapeutic benefits as well as the lack of any major safety problems with the immunotherapy.
“It is estimated that 10% of insulin-producing cells are still alive and working three to six months after diagnosis. According to Imcyse CEO Pierre Vandepapelière, the surviving beta cells would be protected and able to continue producing insulin if the autoimmune process was halted.
ActoBio Therapeutics, a subsidiary of Precigen in the United States and located in Belgium, is now undertaking phase I/II clinical research to use a novel technique to prevent the development of type 1 diabetes. The company uses cheese-making bacteria to deliver two drugs that activate regulatory T cells and teach the immune system not to attack insulin-producing cells.
Pieter Rottiers, CEO of Precigen ActoBio, stated that “it is potentially a safe oral treatment that will be given for a short period of time and could result in patients who develop type 1 diabetes not needing to use insulin, or delaying the need for insulin after diagnosis.”
Automated treatment with an artificial pancreas
For those who have already lost their insulin-producing cells, a “artificial pancreas” — a completely automated device that can assess blood glucose levels and administer the appropriate amount of insulin into the circulation, much like a functional pancreas — may provide a more immediate solution.
Diabetes type 1 is unique from other kinds of diabetes. According to Roman Hovorka, a professor at the University of Cambridge, the quantity of insulin required changes significantly from day to day, and patients cannot possible know how much they need.
His research team hopes to develop an algorithm that can accurately predict an individual patient’s insulin demands in real time and use that knowledge to manage insulin delivery using an insulin pump.
If computers replaced humans, patients could be able to better manage their blood sugar levels and suffer fewer long-term repercussions. Before insulin therapy may be completely automated, a number of obstacles must be resolved. Quicker kinds of insulin are necessary to react to changes in blood sugar levels quickly enough. Furthermore, current algorithms must be considerably improved in order to provide exact forecasts.
Diabetic Type 2
Boosting Insulin Production
“Over 40 new diabetes medications and injections have been approved in the last ten years.” According to Kurt Graves, CEO of Intarcia, the majority of type 2 diabetes patients still have poor glycemic control.
One of the most successful therapies for type 2 diabetes is glucagon-like peptide (GLP)-1 receptor agonists, which boost insulin manufacturing in beta-pancreatic cells while suppressing the release of glucagon, a hormone with the opposite function of insulin.
Every major pharmaceutical firm, including Sanofi, Eli Lilly, Roche, AstraZeneca, and Boehringer Ingelheim, has GLP-1 medications on the market or in the works. However, Novo Nordisk took things a step further in 2019 when it received permission for the first oral version of the GLP-1 medicine semaglutide, which is now accessible.
Poxel, a French company, is exploring a novel technique with a medicine that lowers blood sugar by concurrently targeting the pancreas, the liver, and the muscles. The medicine exhibited this benefit in a phase III research done in Japan, and as a consequence, it was approved in summer 2021. Poxel is planning a phase III research in Europe and the United States for the same medicine, following which it will petition for approval.
Betagenon and Baltic Bio are developing a first-in-class medicine with the ability to simultaneously manage blood sugar levels and reduce blood pressure, a key risk factor in patients with type 2 diabetes who are also obese. The drug is now undergoing Phase II clinical trials.
MorphoSys, a German business, is also targeting the obesity-related part of type 2 diabetes by collaborating with Novartis on phase II research for an antibody that is meant to reduce fat, prevent insulin resistance, and manage binge eating.
Forcefully Striking The Microbiome
Scientists have learned in the past 10 years that the microbes that dwell inside and on us have a substantial influence on our health. Several chronic diseases, including diabetes, have been linked to the human microbiome, namely the gut microbiome.
In 2017, researchers at the University of Amsterdam discovered that faecal transplants, which transfer a healthy person’s microbiota to the stomach of a diabetic, may temporarily improve insulin resistance in type 2 diabetics who are obese. In 2021, patients who had just been diagnosed with type 1 diabetes had similar results.
Some companies are working on diabetes treatments that target the microbiome. According to the French business Valbiotis, a drug aimed to boost microbiome diversity as a treatment for type 2 diabetes in its early stages is now completing phase II/III research.
Although fascinating, the microbiome field is still very young, and because of its complexity, proving causation after detecting connection may be difficult. The real potential of the microbiome in this sector will be impossible to judge until new diabetes treatments are clinically tested.
The needle-free revolution
Diabetes patients are often need to puncture their skin with lancets to monitor their blood sugar levels, which is an unpleasant and painful operation. However, several firms are developing non-invasive alternatives to finger pricking.
Integrity Applications, for example, has developed GlucoTrack, a device that can monitor glucose using electromagnetic waves and is already available in Europe.
Similar technologies are evolving, with MediWise utilising radio waves to monitor sugar levels and DiaMonTec using an infrared laser to fire light through the skin of the finger. According to MediWise co-founder Panos Kosmas, the device “could reduce healthcare costs, which in the case of diabetes account for €90B per year in Europe.”
Patches, such as the FreeStyle Libre, an inch-wide patch that may be worn for up to two weeks and requires a continuous, subcutaneous needle prick to implant the device, are also gaining favour as a non-invasive approach to detect blood glucose. Researchers at the University of Bath are developing a graphene patch that might increase accuracy by monitoring sugar levels individually in different hair follicles.
According to the Dutch firm NovioSense, the little device would be implanted under the eyelid and would be less costly than current continuous glucose monitors.
While FreeStyle Libre has experienced stiff competition, notably in Europe, Senseonics and Roche have developed a three-month glucose monitoring device that is implanted under the skin.
However, accuracy issues with non-invasive blood sugar measurement technologies are common. Four years after Google released its famed glucose-measuring contact lens, it was declared “technically infeasible” and further study would be necessary to match the accuracy of finger-pricking procedures.
What does the future of diabetic care look like?
The market for diabetes drugs is expected to reach €68 billion ($78 billion) by 2026, at which time a slew of ground-breaking technologies are expected to emerge and vie for market share.
Researchers have previously predicted microchips that could detect type 1 diabetes before symptoms appear, nanorobots that could administer insulin while circulating, silica particles that could delay food digestion to prevent diabetes and obesity, and more.
Whatever the future holds, it will undoubtedly have a profound influence on the lives of millions of people worldwide.