The future of diabetes treatment: Is a cure possible?

diabetes treatment cure review

Diabetes has become an epidemic, sentencing over 537 million people worldwide to lifelong medication. Science is striving to find a diabetes treatment that can cure this chronic disease, but how close are we?

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    Diabetes is the major cause of blindness, kidney failure, heart attack, and stroke. It is estimated that the number of people affected by diabetes will rise to 783 million by 2045. This has led the World Health Organization to consider diabetes an epidemic.

    Despite its huge impact on the global population, there is still no cure for any type of diabetes. Most treatments help patients manage the symptoms to a certain extent, but diabetics still face multiple long-term health complications.

    Diabetes affects the regulation of insulin, a hormone required for glucose uptake in cells, resulting in high levels of blood sugar. While there are some similarities in symptoms, the two main types of diabetes develop in different ways.

    Type 1 diabetes is an autoimmune disease that destroys insulin-producing beta-pancreatic cells. In contrast, patients with type 2 diabetes develop insulin resistance, meaning that insulin is less and less effective at reducing blood sugar. 

    The biotech industry is striving to develop new diabetes treatments and chasing the holy grail: a cure. Let’s have a look at what’s brewing in the field and how it will change the way diabetes is treated.

    Type 1 diabetes treatment

    Replacing missing cells with cell therapy

    Cell therapy is one of the biggest hopes for developing a cure for diabetes, especially for type 1 diabetes. Replacing the missing insulin-producing cells could potentially recover normal insulin production and cure patients.

    However, early attempts to transplant pancreatic cells have largely failed, mostly due to immune reactions that reject and destroy the implanted cells. The lack of donors is also a limitation.

    In 2016 the Diabetes Research Institute (DRI) announced the first patient treated with their mini-pancreas solution no longer needed insulin therapy. The platform developed by DRI mimics the natural role of the pancreas, analyzing blood sugar levels and releasing the corresponding amount of insulin.

    “This can be the beginning of a new era in islet transplantation. Our ultimate goal is to prevent the need for lifelong anti-rejection therapy.”

    Camillo Ricordi, Director of the DRI

    A similar approach is being pursued by German firm Evotec, which has a stem cell-based beta cell replacement therapy in preclinical development. Evotec was originally co-developing the therapy with Sanofi but, since Sanofi withdrew from the collaboration last year, Evotec will carry on the development alone. The company is planning to initiate the Phase 1/2 trial in 2024.

    One of the major challenges with cell transplantation therapies has been the need for immunosuppression to prevent the immune system from attacking the transplanted cells. However, a new biomaterial-encapsulation strategy has been developed for type 1 diabetes treatment by a team of scientists at Rice University. This approach does not require immunosuppression and uses biomaterial capsules to protect implanted cells from the immune system. By tagging biomaterial with a unique “barcode” the team can easily assess which biomaterial shows the best compatibility in a live subject.

    Researchers from the Baker Heart and Diabetes Institute in Australia have discovered a method to regenerate insulin-producing cells in the pancreas. This involves using FDA-approved drugs, initially used in cancer treatments, to target the EZH2 enzyme in human tissue. These drugs, GSK126 and Tazemetostat, have shown promise in allowing pancreatic ductal progenitor cells to develop functions similar to beta-cells, which are typically ineffective or missing in people with type 1 diabetes. This approach could reduce the need for insulin injections, as these regenerated cells can sense glucose levels and adjust insulin production accordingly. This breakthrough holds potential for patients with type 1 diabetes of different ages​​ and is one of the most promising cure perspectives for type 1 diabetes.

    The FDA has also approved the first cellular therapy to treat patients with type 1 diabetes in 2023, Lantidra. The treatment is injected into the liver in a single administration. Infused allogeneic islet beta cells release insulin which in some cases is sufficient so the patient doesn’t need to take insulin additionally to the treatment. In the case where the first administration was not sufficient a complementary infection can be performed.

    Attacking the origin with immunotherapy

    In type 1 diabetes, insulin-producing cells are progressively destroyed by the immune system. Stopping this process early enough could preserve the cells and provide a cure.

    That is the goal of Imcyse, a Belgian company running a phase I/II clinical trial with an immunotherapy designed to stop type 1 diabetes by specifically killing the immune cells that destroy the pancreas. A phase I trial showed there were no major safety issues related to the immunotherapy and some clinical benefits were also revealed.  

    The company announced in 2023 the completion of enrollment in the phase II IMPACT trial for IMCY-0098, their most advanced imotope designed to halt the progression of diabetes by stopping the body’s immune system from attacking beta-cells. An imotope is a synthetic peptide containing a T-cell epitope and a thioredox motif. To put it more simply, imotopes target the autoimmune pathway without harming the rest of the immune system. They are expecting efficacy proof-of-concept data in the first quarter of 2024.

    “Early after diagnosis, between three to six months, it is estimated that around 10% of the insulin-producing cells are still alive and producing insulin. After stopping the autoimmune process, the remaining beta cells would be protected and could continue producing insulin.”

    Pierre Vandepapelière, CEO of Imcyse

    Another Belgian company, ActoBio Therapeutics, a subsidiary of the US firm Precigen, is now running a phase I/II clinical trial with an unusual approach to stop the progression of type 1 diabetes. The company uses cheese-producing bacteria to deliver two drugs that stimulate regulatory T cells to instruct the immune system not to attack insulin-producing cells.

    “It is potentially a safe oral treatment that will be given for a limited period of time and could lead to patients who develop type 1 diabetes not needing to use insulin, or delay the need for insulin after diagnosis,” said Pieter Rottiers, CEO of Precigen ActoBio.

    2023 has seen new developments in diabetes immunotherapy. A breakthrough drug for treating children with new-onset type 1 diabetes has shown promising results. Teplizumab, designed to modify the disease’s progression, showed promise in clinical trials, demonstrating the potential to change the standard of care for early-stage type 1 diabetes in young patients. The focus is on preserving the body’s ability to produce insulin, which could significantly impact long-term disease management and patient quality of life. The patients who were administered the drug preserved more of their remaining beta-cells than the ones who received the placebo.

    Furthermore, the acceleration of AI use in drug discovery and repurposing could accelerate research in the area of diabetes immunotherapy.

    Automated treatment with an artificial pancreas

    For people who have already lost their insulin-producing cells, a shorter-term solution could be the ‘artificial pancreas’ — a fully automated system that can measure glucose levels and inject the right amount of insulin into the bloodstream, just like a healthy pancreas would.

    “Type 1 diabetes is very different from your standard disease. Insulin requirements vary greatly from one day to another and there is no way patients can know what they need,” said Roman Hovorka, Professor at the University of Cambridge.

    His research group is working on the development of an algorithm that can accurately predict insulin requirements for a specific patient in real time, which can be used to control insulin delivery via an insulin pump.

    The FDA has also extended its clearance of the Tandem’s closed loop system to two-year-old children and older. The Control-IQ Technology monitors glucose levels and paired with integrated continuous glucose monitors (iCGMs) and alternate controller-enable pumps (ACE pumps) can automatically decrease, increase, or suspend insulin delivery.

    Replacing human monitoring with algorithms could help patients better control their sugar levels and suffer fewer complications in the long term. However, to fully automate insulin therapy, there are several challenges yet to be addressed. First of all, faster forms of insulin are needed to react quickly enough to changes in sugar blood. In addition, current algorithms need to significantly improve to be able to make accurate predictions.  

    Type 2 diabetes treatment

    Stimulating insulin production

    “During the past decade, over 40 new pills and injections were approved for diabetes. However, the scary reality is that the majority of patients with type 2 diabetes still have poor glycemic control,” said Kurt Graves, CEO of Intarcia.

    One of the biggest hits in type 2 diabetes treatment are glucagon-like peptide (GLP)-1 receptor agonists, which induce insulin production in beta-pancreatic cells while suppressing the secretion of glucagon, a hormone with the opposite effect to insulin.

    GLP-1 drugs have been all over the place in 2023 and not only for their benefits toward diabetes. It is showing great promise in cardiovascular diseases as well as obesity. Initially developed to treat type 2 diabetes, GLP-1 agonists gained traction in 2023 when it was discovered that it had beneficial effects on other obesity-related conditions. 

    Two studies have shown the flagrant benefits of these treatments in 2023. 529 people in the U.S. treated with Semaglutide for diabetes and Wegovy for obesity have shown double the heart improvement after 1 year of treatment. Also among 17,000 people with cardiovascular diseases and excessive weight, those taking Semaglutide were 20% less at risk of heart attacks and strokes.

    An innovative development is the creation of combination therapies like Tirzepatide, which intertwines the sequences of GLP-1 and gastric inhibitory polypeptide (GIP) in a single molecule, functioning as a co-agonist. This dual action stimulates insulin secretion, reduces appetite, and impacts fat cells, leading to improved glucose control and weight loss. Research is also exploring a novel GLP-1/GIP/glucagon molecule to further enhance weight loss by increasing energy expenditure​​.

    The traditional dosing for GLP-1-based treatments, which often requires injections, is evolving with new drug delivery systems. Innovations include an orally-available preparation of GLP-1 and a novel hydrogel-based slow-release system that may only need dosing every four months, enhancing convenience and adherence to treatment​​.

    While GLP-1-based treatments have been generally safe in Type 2 diabetes, the newer, more effective drugs and their applications in other diseases necessitate long-term safety studies. Common adverse events include nausea and vomiting, and there are concerns about potential effects in specific settings such as anesthesia, and a need for careful monitoring of drug dosing​​. The cost of these treatments is also a significant hurdle to broader access. At the moment, GLP-1 drugs cost approximately $1,000 per month and must be taken throughout the life of the patient

    Targeting the microbiome

    In the past decade, scientists have realized the big role that the microbes living inside and on us play in our health. The human microbiome, and especially the gut microbiome, has been linked to multiple chronic diseases, including diabetes.

    An unbalanced microbiome composition has been found in patients with diabetes, who tend to have a less diverse gut microbiome as compared to healthy people.

    In 2017, researchers from the University of Amsterdam showed that fecal transplants, used to transfer the microbiome of a healthy person to the gut of one with diabetes, can result in a short-term improvement of insulin resistance in obese patients with type 2 diabetes. In 2021, similar results were shown in patients who had recently been diagnosed with type 1 diabetes. 

    Some companies are developing diabetes treatments targeting the microbiome. In 2023, the French biotech Valbiotis announced the successful completion of the TOTUM 63 clinical study, targeting prediabetes and early stages of type 2 diabetes. The study, conducted at the Institute of Nutrition and Functional Foods (INAF) of Laval University in collaboration with the Quebec Heart and Lung Institute, confirms TOTUM 63’s efficacy in reducing glycated hemoglobin, a key diabetes marker. The mode of action involves reducing inflammation, modulating gastrointestinal hormones, and improving metabolic response after meals.

    Other aspects of the microbiota are being explored and could offer new solutions for diabetes in the future. For instance, the field of pharmacomicrobiomics, which studies the interaction between drugs, microbes, and the host, has gained prominence and could lead to more personalized approaches in type 2 diabetes. Microbiota imbalances and their relation to insulin resistance are also being explored and could give us new areas of research for type 2 diabetes.

    Although promising, the microbiome field is still young and its complexity makes it difficult to establish causation after finding correlation. Until more diabetes treatments are tested in the clinic, it will be difficult to determine the real potential of the microbiome in this space.

    What’s next in diabetes treatment?

    The global diabetes drugs market is expected to reach a massive $118 billion by 2032 according to Precedent Research analysis, and we can expect all sorts of revolutionary technologies to come forward and claim their market share.

    Research is being pursued in the area of nanotechnology. Nanocomplexes (NCs) responsive to glucose levels are increasingly seen as highly promising for the controlled release of insulin. Polysaccharide NP, commonly known as nanosugar or glycogen, stands out as a viable option due to its notable hydrophilicity, its biocompatibility, and the adaptability of its structure.

    More and more companies are invested in treating diabetes and a few innovative actors are poised to advance the field.

    Whatever the future brings, it will undoubtedly make a huge difference in the lives of millions of people worldwide.

    This article was originally published in November 2021 and has since been updated by Jules Adam, on January 15, 2024.

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