In the near-century since the discovery of insulin, the array of treatments for diabetes has expanded to include a wide variety of devices and drug classes. However, one commonalty to all existing treatments is that they manage the condition rather than cure it.
Currently, researchers are exploring several avenues to improve treatment of the disease and perhaps eradicate it. In the short term, much of this activity is centered on improving the utility or efficacy of existing therapeutic approaches. Extend the time horizon and things really get interesting as researchers leverage new genetic tools and gain a more complete understanding of the chemical and biological processes that cause diabetes.
1. Better medicines
As we have seen, insulin products continue to evolve, often through new formulations of the drug itself. One long-sought goal is to create long-acting insulin which is engineered to modulate its potency to respond to a patient’s blood sugar levels and insulin needs. Known as glucose-responsive insulin (GRI), such a product would remain in the blood for an extended time but become active only when needed in response to a meal.1 Researchers are now using advanced computer models to help identify the chemicals needed for a GRI.2
In addition to better insulin, researchers are investigating new methods of drug delivery to move beyond needles and avoid injections altogether.3 Eagerly-awaited but remaining stubbornly over the horizon, oral insulin would bring many benefits, including ease of use, more precise control over glucose levels and reduced risk of hypoglycemia.4 At the population level, oral insulin is sought after as a way to increase adherence and compliance, which is seen as crucial in lowering overall diabetes-related spending.
Nonetheless, drug manufacturer Novo Nordisk cancelled plans to bring an insulin pill to market last year even though the oral formulation had shown early clinical promise.5 One primary challenge with oral insulin is bioavailability, which refers to the degree and rate at which an administered drug is absorbed into the blood. Because it is administered through the digestive system, the bioavailability of oral insulin is difficult to calculate on a per-dose basis.6 For example, the rate and extent of insulin absorption could vary widely according to what is in a person’s stomach.7
Even with these bioavailability issues addressed, the company could face trouble recouping their considerable development costs despite the perceived advantages of oral insulin. In an increasingly price-conscious insulin market dominated by well-established injectable variations, charging a premium price for an oral version would be difficult.5
Opting to leverage existing medications, the company has instead focused its efforts on Xultophy, an injectable drug which combines the long-acting basal insulin Tresiba® with a glucagon-like peptide-1 receptor agonist, Victoza®.8
2. Technological solutions
Much as drug companies are combining diabetes drugs in order to improve efficacy, medical device makers are joining existing products together to improve treatment. Such is the case with the artificial pancreas, which combines existing treatments and technologies in a single device. In November of 2016, the FDA approved a version of a closed loop system from Medtronic, which uses elements of glucose monitors, insulin pumps and wireless devices, to monitor and subcutaneously deliver a variable rate of insulin to a diabetic 24 hours a day.9
The practical and clinical benefits of real-time, continuous glucose monitoring are numerous, including limiting the amount of time people spend with elevated blood sugar levels.10
Many of broader technology trends that have reshaped our world recently, such as ever-shrinking electronics, artificial intelligence, and ubiquitous wireless technology are showing up in diabetes care. Interestingly, many of the top technology companies in the world are working directly on diabetes care.
Verily, a unit of Google parent Alphabet Inc., is working on contact lenses to monitor glucose.11 To help type 2 diabetics, retail giant Amazon is teaming with drug maker Merck to develop voice-enabled apps for Amazon’s digital assistant, Alexa.12 Notoriously-secretive, Apple is said to have a team of biomedical engineers developing non-invasive sensors to monitor glucose.13
3. From palliative to curative
As revolutionary as an artificial pancreas or glucose-detecting contact lenses are, from a therapeutic and cost perspective they are still half-measures that merely alleviate or monitor symptoms of the disease, rather than curing it. While these advances will do much to improve the quality of life of a diabetic, that person will remain a diabetic.
So, can we cure diabetes outright? The answer to that question is rapidly evolving as cell therapies, surgeries and even some vaccine-based approaches are showing increasing promise.
To cure type 1 diabetes, which occurs when the body’s immune system attacks insulin-producing cells in the pancreas, some researchers are looking to use existing therapies for unrelated ailments in novel ways. Take bone morphogenetic proteins (BMPs), which are FDA–approved and commonly used to stimulate bone growth after oral surgeries. Researchers want to use BMPs as a way to “reprogram” the impaired pancreatic cells, known as beta cells, so that they begin to start producing insulin again.14
Similarly, scientists are looking to repurpose a vaccine developed over 100 years ago for the prevention of tuberculosis to fight type 1 diabetes. The vaccine, bacillus Calmette-Guérin (BCG), may be able to improve insulin production in people who have small but detectable levels of insulin coming from their pancreas.15 Elsewhere, a team in Finland is investigating the use of a new vaccine to thwart a type of virus believed to play a role in triggering the initial immune attack on beta cells.16
More experimentally, some researchers are looking at using cutting-edge gene editing tools such as CRISPR to find a genetic fix for beta cell destruction.17 One approach discussed relies upon a type of immunotherapy. Stem cells would be collected from a patient’s dental pulp or bone marrow. The cells are subsequently genetically modified and transdifferentiated into insulin-producing beta cells which are less likely to elicit the autoimmune response inherent to diabetes. These artificial pancreatic cells would then be reinserted into the patient’s body subcutaneously.18
For type 2 diabetes, a promising albeit invasive option now being explored is surgery. Interestingly, here doctors are targeting other parts of the digestive system instead of the pancreas itself. Surgeons note that existing weight-loss surgeries can help treat type 2 diabetes but are still seeking to identify the exact therapeutic mechanism or mechanisms at work.
By reducing the surface area of the gastrointestinal tract, commonly used bariatric surgeries such as gastric bypass alter bile acids, the secretion of gut hormones and the community of microbes living in the intestines, all of which could potentially impact the body’s reaction to blood sugar.19 Encouragingly, researchers are now investigating methods to mimic the end results of these surgeries without actually cutting into patients.19
Taken as whole, these avenues of inquiry offer a great deal of encouragement for the future of diabetes care. In the meantime, a holistic approach to treating diabetes is essential, notes Savitha Vivian, VP of Clinical Services for OptumRx.
As promising as many of these advances are, it is important to note that many are speculative and only likely to pay dividends far down the road...– Savitha Vivian, VP of Clinical Services for OptumRx
“As promising as many of these advances are, it is important to note that many are speculative and only likely to pay dividends far down the road,” she says. “Currently, the only sound policy is to focus on individualized diabetes treatment using the optimal combination of behavior modification, healthy lifestyle and the drugs we have.”
Given this, the next article in this series will explore the array of comprehensive management strategies now available to lower the total cost of care and improve outcomes for patients with diabetes.
STATEMENT REGARDING FINANCIAL INFLUENCE:
This article is directed solely to its intended audience about important developments affecting the pharmacy benefits business. It is not intended to promote the use of any drug mentioned in the article and neither the author nor OptumRx has accepted any form of compensation for the preparation or distribution of this article.
- Nature Chemistry. “Glucose-responsive insulin by molecular and physical design.” Accessed at: http://www.nature.com/nchem/journal/v9/n10/full/nchem.2857.html?foxtrotcallback=true
- MIT News. “Model predicts performance of glucose-responsive insulin.” Accessed at:
- The Journal of Diabetes Science and Technology. “Oral Insulin and Buccal Insulin: A Critical Reappraisal.” Accessed at:
- The Journal of Diabetes Science and Technology. “Oral Insulin: The Rationale for This Approach and Current Developments” Accessed at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769870/
- Pharmaphorum. “Oral insulin could still be a reality, says Novo Nordisk” Accessed at: https://pharmaphorum.com/news/oral-insulin-still-reality-says-novo-nordisk/
- Expert opinion on drug delivery. “Enhancement of oral insulin bioavailability: in vitro and in vivo assessment of nanoporous stimuli-responsive hydrogel microparticles.” Accessed at: https://www.ncbi.nlm.nih.gov/pubmed/26943455
- American Chemical Society. “Insulin pill could make diabetes treatment ‘ouchless’” Accessed at: https://www.acs.org/content/acs/en/pressroom/newsreleases/2016/august/isulin-pill-could-make-diabetes-treatment-ouchless.html
- FiercePharma. Novo's Xultophy beats basal-bolus insulin at cutting hypoglycemia, spurring weight loss. Accessed at: http://www.fiercepharma.com/pharma/novo-nordisk-s-xultophy-beats-basal-bolus-therapy-at-lowering-hypoglycemia-weight-gain
- Reuters. “FDA approves Medtronic's 'artificial pancreas' for diabetes” Accessed at: http://www.reuters.com/article/us-health-diabetes-medtronic-idUSKCN11Z04Y
- The Journal of Diabetes Science and Technology. “Recommendations for Using Real-Time Continuous Glucose Monitoring (rtCGM) Data for Insulin Adjustments in Type 1 Diabetes” Accessed at: http://journals.sagepub.com/doi/full/10.1177/1932296816663747
- Verily. “Smart Lens Program” Accessed at: https://verily.com/projects/sensors/smart-lens-program/
- FiercePharma. “Alexa, help manage my diabetes” Accessed at: http://www.fiercepharma.com/marketing/merck-taps-five-finalist-its-alexa-diabetes-contest-to-invent-voice-enabled-solutions
- CNBC. “Apple has a secret team working on the Holy Grail for treating diabetes” Accessed at: http://www.cnbc.com/2017/04/12/apple-working-on-glucose-sensors-diabetes-treatment.html
- Diabetes Research Institute. “DRI Makes a Big Step Forward with Reprogramming Cells to Create Islets” Accessed at: https://www.diabetesresearch.org/Reprogramming-Islets
- Science Daily. “Potential mechanism for BCG vaccine reversal of type 1 diabetes” Acessed at: https://www.sciencedaily.com/releases/2017/06/170610134818.htm
- University of Tampere. “A preventive vaccine for Type 1 Diabetes to be studied in humans for the first time” Accessed at: https://www.uta.fi/en/news/story/preventive-vaccine-type-1-diabetes-be-studied-humans-first-time
- Science Daily. “CRISPR editing in pancreatic cells reduced cell death, increased insulin secretion” Accessed at: https://www.sciencedaily.com/releases/2016/12/161201093003.htm
- Stem Cell Research & Therapy. “CRISPR-targeted genome editing of mesenchymal stem cell-derived therapies for type 1 diabetes: a path to clinical success?” Accessed at: https://stemcellres.biomedcentral.com/articles/10.1186/s13287-017-0511-8
- Scientific American. “Why the Most Powerful Treatment for Diabetes Turns Out to Be Surgery.” Accessed at: https://www.scientificamerican.com/article/why-the-most-powerful-treatment-for-diabetes-turns-out-to-be-surgery/