Assessing Diabetes Treatment Options

Diabetes continues to hold a place among the most prevalent chronic diseases in the United States with the Centers for Disease Control and Prevention reporting that 30.3 million people are currently living with disease in the United States.¹ This is a condition that does not discriminate based on sex and although more prevalent in middle to older age groups, can be found in patients of any age.²

As many likely know, there are two main types of diabetes. Type 1 diabetes can be generally defined as a condition where insulin is not produced by the pancreas due to autoimmune attack or other defects in beta-cell function with onset commonly occurring in childhood. Type 2 diabetes, on the other hand, is usually caused by a combination of insulin resistance and potentially decreasing insulin production over time. 

While type 2 was traditionally thought of as a disease of adulthood, an increasing number of teens are being diagnosed with the condition, tied to obesity and unhealthy lifestyles.³ Both types of diabetes lead to an increase in blood glucose that if left untreated can cause a number of acute and chronic symptoms. The most concerning of the chronic symptoms is the organ damage that leads to conditions like heart disease, kidney disease, and microvascular complications.

In addition to the significant burden on patients, diabetes inflicts a high economic burden for the United States. The treatment costs continue to climb year-over-year with estimates rising from $245 billion in 2012 to $327 billion in 2017.⁴ The high prevalence, patient and economic burden make this a disease state commanding a large amount of attention in the medical, patient advocacy, and managed care communities.

Clinical Guidelines

The American Diabetes Association releases treatment standard guidelines on an annual basis, with supplemental updates released as needed based on new scientific evidence or regulatory changes requiring timely inclusion.⁵ The standards address the treatment of both type 1 and type 2 diabetes focusing on a balance of all aspects of treatment including prevention, diagnosis, lifestyle modifications, appropriate health care professional team involvement in patient care, pharmacologic therapy, and appropriate goals of care.

The pharmacologic treatment standards for type 1 diabetes focus mainly on replacement of insulin while acknowledging ongoing studies of other potential treatment. It is recommended that most patients received either a regimen of basal (long-acting) and bolus (short-acting) insulin through multiple daily injections or by using a subcutaneous continuous infusion insulin pump. The guidelines also mention that pancreas and islet transplantation may be considered for patients who have failed intensive insulin therapy, are undergoing a simultaneous renal transplant, or who have previously undergone renal transplant.

As type 2 diabetes is caused by a combination of insulin resistance and possible decreases in insulin production over time, the pharmacologic treatment options include many classes of drugs beyond insulin replacement. The guidelines have consistently recommended metformin as the first line option for most patients and recommends that metformin use continues even as other medications are added to a patient’s regimen. 

Until recently, the guidelines have not made strong statements of drug class preference after metformin for the majority of patients. Based on recent evidence, the guidelines now recommend a glucagon-like peptide-1 (GLP-1) agonist or sodium sodium-glucose cotransporter-2 (SGLT2) inhibitors with proven cardiovascular benefit in patients with atherosclerotic cardiovascular disease or an SGLT2 inhibitor with proven cardiovascular benefit in patients with heart failure or kidney disease as the second-line treatment behind metformin. 

In addition to these updated recommendations in patients with specific comorbid conditions, all patients with type 2 diabetes who require the greater efficacy of an injectable medication in order to reach treatment goals after oral therapy should receive a GLP-1 agonist ahead of insulin. This recommendation is due to the positive effects on body weight and the lower risk of hypoglycemia GLP-1 agonist drugs have over insulin therapy. 

The guidelines also recognize that many patients will require the eventual use of insulin to control type 2 diabetes. For these patients, the guidelines allow the provider and patient to choose insulin type and regimen based on patient need, convenience, cost, and other relevant factors.

The Future of Diabetes Treatment

Development of improved treatments options for patients with diabetes is ongoing. The so-called artificial pancreas, or a closed loop continuous glucose monitor and subcutaneous insulin pump, designed to automatically monitor blood glucose levels and adjust insulin delivery continues to undergo development and improvement.^6-8 

While some patients have found the current closed loop system available on the market to work well for them, others have found difficulty in using the auto-mode due to frequent alarms, calibration requirements, supply issues, and other similar concerns.⁹ As new generations of systems become available that work to overcome these challenges, many are hopeful that they will become the new standard in delivery of insulin treatment.

An oral GLP-1 agonist drug is currently under FDA review.¹⁰ This drug is co-formulated with a molecule that provides a local buffering effect in the stomach protecting the peptide from degradation and allowing the absorption of the GLP-1 through the stomach lining.¹¹ If approved, this product may allow patients with needle phobia, or with other factors causing the inability to use an injectable medication, to receive the benefits of a GLP-1 that are currently out of their reach. ν

References:

1. Centers for Disease Control and Prevention. National Diabetes Statics Report, 2017. https://www.cdc.gov/diabetes/data/statistics/statistics-report.html. Accessed May 6, 2019.
2. Centers for Disease Control and Prevention. Prevalence of Both Diagnosed and Undiagnosed Diabetes, 2017.  https://www.cdc.gov/diabetes/data/statistics-report/diagnosed-undiagnosed.html. Accessed May 6, 2019.
3. Reinehr T. Type 2 diabetes mellitus in children and adolescents. World J Diabetes. 2013;4(6):270–281. doi:10.4239/wjd.v4.i6.270
4. American Diabetes Association. The Cost of Diabetes. https://www.diabetes.org/advocacy/news-events/cost-of-diabetes.html. Published January 30, 2019. Accessed May 6, 2019. 
5. American Diabetes Association. Practice Guidelines Resources. 2019. https://professional.diabetes.org/content-page/practice-guidelines-resources. Accessed May 6, 2019.
6. Medtronic. Medtronic receives FDA breakthrough designation for developing personalized closed loop insulin pump system for diabetes management. 19 February 2019. https://newsroom.medt
ronic.com/phoenix.zhtml?c=251324&p=irol-newsArticle&ID=2387843. Accessed May 6, 2019.
7. The Bionic Pancreas Team. Outpatient and Home-Use Clinical Trials. 2014. https://sites.bu.edu/bionicpancreas/clinical-trials/. Accessed May 6, 2019. 
8. Tandem Diabetese Care. Inovations in progress: changing the face of insulin pump therapy.  https://www.tandemdiabetes.com/about-us/pipeline. Accessed May 6, 2019. 
9. Medpage Today. Over one-third T1D patients bail on closed-loop system. March 24, 2019. https://www.medpagetoday.com/meetingcoverage/endo/78769. Accessed May 6, 2019.
10. Novo Nordisk files oral semaglutide for US regulatory approval of glycaemic control, as well as for CV risk reduction for oral semaglutide and Ozempic®[news release]. Bagsværd, Denmark March 20, 2019. https://www.novonordisk.com/content/Denmark/HQ/www-novonordisk-com/en_gb/home/media/news-details.2239031.html. Accessed May 6, 2019.
11. Buckley ST, Bækdal TA, Vegge A, et al. Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist. Sci Transl Med. 2018 14 November;10(467).doi: 10.1126/scitranslmed.aar7047.