Five advancements in diabetes treatment to watch

Nearly 86 million Americans have pre-diabetes and another 30 million have diabetes; roughly 1 million individuals are added to these figures each year, according to the American Diabetes Association (ADA). The overall cost annually to treat pre-diabetes and diabetes in the United States has escalated to $322 billion. In fact, one-third of all Medicare dollars are spent caring for people with diabetefs and overall, 20% of all healthcare dollars are spent caring for people with this disease.

Just like the number of diabetes cases continues to increase, the cost of diabetes treatment and medications is rising. Many people with diabetes have multiple complex comorbidities (e.g., heart disease, high blood pressure, high cholesterol, and obesity), which also require intensive management. Diabetes patients incur medical expenses that are 2.3 times higher than those without diabetes and their average medical expenditures are about $13,700 per year, of which some $7,900 are attributed directly to diabetes, according to the ADA.

Pantalone

In addition, many of these patients require newer and/or more expensive therapies, such as insulin. “A significant increase in the cost of vital diabetes medications has occurred over the past few decades, particularly with insulin therapy,” says Kevin M. Pantalone, DO, staff endocrinologist and director of clinical research, Department of Endocrinology, Cleveland Clinic, Cleveland, Ohio. “This has caused significant difficulty in getting patients the medications they need, especially those who are on a fixed income and Medicare patients who lose drug coverage when they hit their insurance coverage gap (i.e., the ‘donut hole’).”  

Depending on their type of insurance coverage-such as those with high-deductible plans-many patients with diabetes cannot afford some of the newer therapies that may provide numerous benefits over older medications such as sulfonylureas, Pantalone continues. Newer medications (dipeptidyl peptidase 4 [DPP-4] inhibitors, glucagon-like peptide 1 receptor agonists [GLP-1RA], and sodium-glucose co-transporter 2 [SGLT-2] inhibitors) are not associated with an increased risk of hypoglycemia (low sugar levels) and are either associated with weight loss or are weight neutral.

The healthcare industry continues to focus efforts on treatments that work better, and ideally are less expensive and less invasive for patients.

Next: A closer look

Here’s a close look at five advances in diabetes treatments, including new medications and those in the pipeline.

1.              Glucose monitoring devices

Continuous glucose monitoring (CGM) and connected blood glucose monitoring (cBGM) devices provide actionable data to guide people with diabetes and their providers. “As a technology, CGM provides nearly continuous glucose measurements in real time, which translates to almost 300 readings a day for providers to review and respond [to] with therapeutic adjustments,” says Andrew S. Rhinehart, MD, chief medical officer, Glytec. “Presently, CGM is mainly used for individuals with type 1 diabetes, but that may change over time depending upon reimbursement and outcomes data for people with type 2 diabetes.”

Lucas

New CGM systems, such as the Dexcom G5 Mobile CGM system and Abbott’s FreeStyle Libre, consist of a small disposable sensor that is inserted into the skin. A transmitter connected to the sensor wirelessly sends results to a receiver that displays real-time glucose information, explains Stephenie Lucas, MD, medical director of the diabetes treatment center at Beaumont Health, Grosse Pointe, Michigan. These devices require fingersticks as infrequently as twice a day for calibration and users can safely and conveniently access and share their dynamic glucose data anywhere and anytime.

FreeStyle Libre is now available across 32 countries around the world, although still under FDA review in the U.S.  The professional version of the system, FreeStyle Libre Pro, is approved in the U.S. and was launched toward the end of 2016.

cBGMs include meters with cellular or Bluetooth capabilities that allow blood glucose data to be transmitted to the cloud, making it easily accessible to providers. “This allows for better patient engagement, and if acted upon properly, better patient outcomes,” Rhinehart says. The first cellular meter was launched by Telcare in 2010.

Diabetes therapy management software with decision support for dosing and titration is the final piece of the therapeutic puzzle. In concert with data made available through CGM and cBGM, this software can help providers properly dose and titrate diabetes medications, especially insulin, and choose which diabetes mediations may work best for each patient.  Diabetes therapy management software, in its earliest form, was launched by Glytec in 2006.

“For most providers, this is the most challenging aspect of diabetes management, but also the most important,” Rhinehart says. “Having providers choose the right medications and making the necessary dosing adjustments in a timely manner is critical to achieving and maintaining acceptable A1c levels. The combination of connected devices and this type of therapy management software may be the holy grail of personalized diabetes management.”

Next: Another advancement

2.              Artificial pancreas

Innovative companies are making great strides in the development of the artificial pancreas. Although these systems do not replace the pancreas, they closely mimic a healthy pancreas’ glucose regulating function. These systems can administer insulin when sugar levels are elevated and discontinue insulin when sugar is low. This minimizes the risk of serious low and high blood sugars. 

One advancement debuting in the United States in April is the hybrid artificial pancreas. The system, designed for use with Medtronic's MiniMed 670G insulin pump (approved by the FDA in September 2016), automates basal insulin delivery to maximize the time glucose levels are in a healthy range throughout the day and night. “The system will give many people with diabetes new freedom and peace of mind as for the first time, they may be able to sleep through the night without periodically waking up to check and manage their blood glucose levels,” Lucas says.

A study published in JAMA found that on the 670G system, 124 patients had no episodes of severe hypoglycemia or ketoacidosis over 12,389 patient days. Further, the 670G system kept people with type 1 diabetes within their desired blood sugar range 73.4% of the time, compared to 67.8% without the system. At night, the most dangerous time for blood sugar highs and lows, the difference was even more pronounced-76.4% of readings were in range versus 67.8% without the system.

Adimoolam

An artificial pancreas system consists of three devices that closely mimic the glucose regulating function of a healthy pancreas, says Deena Adimoolam, MD, assistant professor of medicine, endocrinology, diabetes, and bone disease at the Icahn School of Medicine at Mount Sinai, New York. These devices include:

·               A motorized infusion pump which can deliver two important hormones-insulin and glucagon;

·               ACGM to evaluate blood glucose throughout the day; and

·               A glucometer, as the patient needs to check fingersticks at least twice daily to calibrate the continuous glucose monitor.

These systems communicate directly with one another through a sophisticated computer-controlled algorithm. “Ultimately, the glucose values detected by the CGM determine whether or not the pump gives the patient insulin to decrease glucose values or glucagon to increase glucose values; therefore, keeping blood glucose values in a target range,” Adimoolam says.

Another type of artificial pancreas under development is the bionic pancreas. This CGM and pump system is scheduled to undergo a large clinical trial, and is not yet approved by the FDA. It consists of an insulin-only system, as well as a system that uses two hormones-glucagon and insulin-within the pump system, in conjunction with the CGM.

“The system controls the patient’s blood sugar; the patient only has to perform a few blood glucose checks per day in order to calibrate the CGM device,” Pantalone says. “Mathematical algorithms use the CGM information to continually adjust the rates of hormone infusion in order to obtain better blood sugar control.” 

Next: Medications are key

3.              Medications to treat both diabetes and cardiovascular disease

For the first time, medical evidence supports a cardiovascular risk reduction treatment associated with some anti-diabetic therapies: two GLP-1 receptor agonists-liraglutide (currently available) and semaglutide (began the FDA approval process in December 2016), and one SGLT-2 transport inhibitor-empagliflozin.

“These cardiovascular outcomes trials were published in 2015 and 2016 and were groundbreaking,” Pantalone says. “For the first time, some diabetes drugs were demonstrated to have an effect beyond simply lowering blood sugar levels. This is very important, as cardiovascular disease is the number one cause of death in patients with diabetes type 2. If a therapy can lower blood sugar levels and simultaneously potentially lower a patient’s risk of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke, it would be preferred to use these therapies in patients considered high risk (those with established cardiovascular disease or those with numerous risk factors for cardiovascular disease).”  

In a clinical study published in The New England Journal of Medicine using the SGLT-2 inhibitor empagliflozin in type 2 diabetes patients with pre-existing heart disease, researchers reported a 38% risk reduction in cardiovascular death and a 35% risk reduction in heart failure hospital admissions. No significant reduction in heart attack or stroke was noted, however.

“Mechanistically, this continues to be explored, but it is the first drug class with well-managed modern background therapy in diabetes to show total mortality reductions,” says Curtis Triplitt, PharmD, associate professor of medicine, University of Texas Health Science Center at San Antonio. “Whether all type 2 diabetes cardiovascular patients should receive empagliflozin is currently being debated.”

In another clinical trial published in The New England Journal of Medicine, liraglutide, a GLP-1 receptor agonist, reported a 15% reduction in all-cause mortality, but most relate this to a cumulative effect of reductions from heart attack and strokes, Triplitt says. Upon further analysis, patients who took the drug as prescribed received the cardiovascular benefit. Both empagliflozin and liraglutide also reported improvements in renal outcomes; further strengthening their potential use in therapy.

The cardiovascular outcome trials of the remaining FDA-approved GLP-1RA (exenatide once weekly, albiglutide, and dulaglutide), and the other SGLT-2 transport inhibitors (canagliflozin and dapagliflozin) are still in progress and should conclude over the next few years. “If these studies find similar results, that would be something to watch, as we can then say that the observed cardiovascular risk reduction is actually a class effect, and not specific to just a few agents within the class,” Pantalone says.

Next: Insulin matters

4.              Concentrated insulin

Another advancement stems from the development of more concentrated insulins to benefit patients who have difficulty absorbing insulin. The most commonly prescribed insulins are known as “U100” insulin, in which there are 100 units of insulin in 1 milliliter of fluid.

“Some diabetics are quite insulin resistant and require high doses of insulin,” says Adimoolam. “We suspect that when insulin is injected at high volumes, it’s possible that 100% is not absorbed. Therefore, the patient is not getting the true amount of insulin being prescribed and their glucose values remain elevated.”

Concentrated insulins, referred to as “U200,” “U300,” or “U500,” can provide much more insulin per 1 milliliter of liquid. For example, U200 consists of 200 units of insulin per milliliter, U300 consists of 300 units of insulin per milliliter, and so forth. These insulins became publicly available in 2016.

“Concentrated insulins are better absorbed than U100 insulins because absorption of insulin is improved,” Adimoolam explains. “Concentrated insulins have helped improve diabetes control in those who take a significant amount of insulin (more than 40 units daily). Concentrated insulins cause less hypoglycemia in comparison to U100 insulin.”

5.              Cell-based therapies

Some challenges related to pancreas transplants are the ability to harvest enough pancreatic cells and the ability to stop the body’s immune system from destroying these cells. Progress has been made in stem cell research and efforts to reprogram tissue-specific cells to overcome these barriers.

“A number of surgical advances have improved the early success rate of transplantation, and modern immunosuppressive strategies have improved the rate of longer term survival of tissue grafts,” Lucas says.

Karen Appold is a medical writer in Lehigh Valley, Pennsylvania.