New diabetes medications help address linked diseases

Diabetes medications were the most expensive among traditional therapy drug classes with an overall trend of 14% in 2015, according to the Express Scripts 2015 Drug Trend Report. The positive trend is reflective of increases in both utilization and unit cost.

“Diabetes is a national epidemic with more people being diagnosed on an annual basis” says April Kunze, PharmD, senior director, clinical formulary development and trend management strategy, Prime Therapeutics. “Overall, Prime has seen a 20% increase in trend from the third quarter of 2015 to that of 2016. This is driven by approximately a 7% increase in utilization and a 12% inflationary increase.”

An increase in brand drug use is contributing to the spend, Kunze explains. Prime is seeing more use of glucagon-like peptide-1 receptor agonists (GLP-1s), sodium-glucose co-transporter 2 (SGLT-2) inhibitors and dipeptidyl peptidase 4 (DPP-4) inhibitors and less use of low-cost generics, such as the sulfonylureas. Insulin is also a mainstay in therapy, with the basal insulins such as insulin glargine (Lantus, Sanofi) and insulin detemir (Levemir, Novo Nordisk) garnering a significant portion of the utilization and spend.

The Drug Trend Report also predicts that diabetes will continue to be a significant contributor to trend as new cases continue to occur with approximately 27.8% of adults with diabetes currently undiagnosed. Additionally, as type 2 diabetes progresses, patients may require more than one therapy to adequately control the disease. As patients switch from older regimens that require multiple tablets per day to new combination products, increased spend is anticipated, since these combination therapies are branded.

Diabetes drugs that lower CVD risk

Diabetes and cardiovascular disease (CVD) are intimately linked, according to Kathleen Kaddis, BS, PharmD, senior clinical pharmacist, Priority Health.

According to the CDC, death from cardiovascular disease is 70% higher in adults with diabetes, and patients with diabetes have a decreased life expectancy driven in large part by premature cardiovascular death.

“Some argue that diabetes is a metabolic disease with cardiovascular complications, while others claim that it is a cardiovascular disease with metabolic complications,” Kaddis says. “Regardless of your opinion, management of diabetes and cardiovascular risk is of utmost importance. Diabetic patients are given medications for glycemic control, as well as for treatment and prevention of cardiovascular risk factors, like aspirin and statins. Cardiovascular morbidity and mortality are still too common in diabetics.”

Recently, empagliflozin (Jardiance, Boehringer Ingelheim) was the first diabetes drug shown to decrease cardiovascular mortality, says Kaddis. The FDA recently approved Jardiance’s secondary indication to reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and cardiovascular disease.

Empagliflizon also decreased hospitalization and death from heart failure, says Kaddis. “While other diabetes drugs have been able to show neutrality with regard to CVD outcomes, this is the first one to show a significant decrease.”

Novo Nordisk’s liraglutide (Victoza) significantly reduced the risk of major cardiovascular events and death in adults with type 2 diabetes in the Liraglutide Effect and Action in Diabetes - Evaluation of Cardiovascular Outcome Results trial. Results from the trial, conducted at 410 sites in 32 countries, showed that, over a mean of 3.8 years, the glucagon-like peptide 1 receptor agonist Victoza, reduced risk for three-point major adverse cardiac events by 13%, for all-cause death by 15% and for CV death by 22% vs. placebo, while reducing HbA1c and body weight.

“The results showed very impressive results including a 13% lower overall risk of having a heart attack, stroke or death from cardiovascular disease,” says Andrew Lyle, director of business development at Curexa Pharmacy. “Overall, there was a 22% lower risk of cardiovascular mortality and a 15% lower risk of all-cause death.

Next: New medications make a positive impact

New medications make a positive impact

While diabetes continues to the be the number one driver of non-specialty pharmacy cost trend, drug treatment has not advanced significantly over the last few years, explains Nadina Rosier, health and group benefits practice leader at Willis Towers Watson.

According to Rosier, drugs approved in 2016 were largely considered “me-too” products and/or combinations comprised of existing drugs. One is Xultophy (Novo Nordisk), a once-daily fixed dose combination of Tresiba (insulin degludec) and Victoza, indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. Xultophy is expected to launch in the first half of 2017.

Also noteworthy is a device recently approved by the FDA known as the “artificial pancreas.” The MiniMed 670G (Medtronic), is is intended to automatically monitor glucose and provide appropriate basal insulin doses in patients aged 14 years and older with type 1 diabetes, according to the FDA.

Another new therapy that came to the market in 2016 was lixisenatide (Adlyxin, Sanofi), GLP-1 receptor agonist, a hormone that helps normalize blood sugar levels.

Lyle cites the December 2015 approval of Eli Lilly’s and Boehringer Ingelheim’s Basaglar 100 units/mL (insulin glargine injection), a long-acting insulin with an identical amino acid sequence to Lantus another U-100 insulin glargine.

“Unfortunately, there may not be a huge discount on price, but due to rebates to the PBMs, there will be much better formulary placement and easier access for patients who need Lantus,” Lyle says.

Kaddis says diabetes can be individualized to a greater degree than ever before. “With more drugs in the armamentarium, the diabetes team can work with the patient for improved management and glycemic control.”

Pipeline treatments

Anticipate more introductions to the already established classes of diabetes medications as well as the introduction of new classes of drugs, says Kaddis. “Biosimilars to insulin may be hitting the market soon, which will hopefully provide some relief to the drastic price increases that insulin has had in the past few years,” she says.

Rosier cites several novel phase 3 pipeline agents:

Semaglutide (Novo Nordisk), an investigational GLP-1 analogue administered once-weekly, which significantly reduced the risk of the primary composite end-point of time to first occurrence of either cardiovascular (CV) death, non-fatal myocardial infarction (heart attack) or non-fatal stroke by 26% vs placebo, when added to standard of care in 3,297 adults with type 2 diabetes at high CV risk.

Bexagliflozin (Theracos), a highly specific SGLT2 inhibitor for the treatment of type 2 diabetes, which works by diverting excess blood sugars out through the urine to harmonize glucose levels in patients.

Sotagliflozin (Lexicon Pharmaceuticals), a first-in-class, oral dual SGLT1 and SGLT2 inhibitor for Type 1 diabetes. The drug is also in phase 2 for type 2 diabetes.

Another drug to watch is ertugliflozin (Merck and Pfizer), an investigational oral SGLT2 inhibitor for the treatment of patients with type 2 diabetes, according to Lyle. “In September 2016, the companies announced that the therapy met its primary end-point of A1c reduction. The drug is in phase 3 and is expected to be available sometime in 2017,” he says.

Some upcoming therapies are new combinations of existing medications. Combination products being studied include ertugliflozin plus sitagliptin (Merck and Pfizer), ertugliflozin plus metformin (Merck and Pfizer), as well as linagliptin plus pioglitazone (Boehringer Ingelheim and Eli Lilly).

Stem cell research is also looking into potential cures for diabetes by stimulating production of insulin-producing beta cells or injecting insulin-producing cells that would work for up to a year or more, says Kaddis.

Erin Bastick, PharmD, RPh, is a graduate intern at University Hospitals Elyria Medical Center in Elyria, Ohio.