It may not incite the same amount of fear as cancer, but diabetes is a growing problem within the United States. According to the 2014 National Diabetes Statistics Report from the Centers for Disease Control and Prevention, some 29.1 million people in the United States have diabetes (based on 2012 data). This works out to around 9% of the U.S. population.
Of these 29.1 million people, 90% to 95% have type 2 diabetes, which is characterized by the body's inability to properly utilize insulin, leading to glycemic imbalances. Type 2 diabetes tends to develop over time and is potentially reversible if caught in the prediabetes stage. Left untreated, though, type 2 diabetes can lead to a host of co-morbidities, or even death. The CDC lists diabetes as the seventh leading cause of death based on data from 2014, with 76,488 deaths directly attributed to the disease.
Diabetes can also be quite a strain on the healthcare system and patients' pocketbooks. A PhRMA report from 2014 pegged the total cost of diabetes in the U.S. at $245 billion, which includes $176 billion in direct medical costs and $69 billion in indirect costs, such as missed work or premature death that leads to reduced economic productivity. PhRMA also notes that a typical year of diabetes medications can run a patient about $4,110.
New treatment options emerge for type 2 diabetes
One of the current standard-of-care medications for type 2 diabetics is Merck's (NYSE:MRK) Januvia, a DPP-4 inhibitor. DPP-4 inhibitors work to increase incretin levels, which in turn reduce glucagon, an elevator of blood sugar levels. With glucagon suppressed, insulin production increases, leading to improved glycemic balance. In a long-term cardiovascular study involving Januvia known as TECOS, the drug was shown not to increase major adverse cardiovascular events compared to a placebo, which was the primary endpoint.
However, a next-generation class of therapy known as SGLT-2 inhibitors represents a potentially new path forward for type 2 diabetes patients. Instead of working through the pancreas or liver, as prior type 2 diabetes medications have done, SGLT-2 inhibitors work with the kidneys to suppress glucose absorption. By suppressing this absorption, SGLT-2 inhibitors allow the patient to remove excess glucose through their urine, thus achieving improved glycemic balance.
More importantly, during clinical trials throughout the SGLT-2 space, a pretty discernible trend of weight loss (Januvia is a weight-neutral drug) was witnessed, as well as lower systolic blood pressure, for patients taking these drugs. Being overweight or obese doesn't guarantee you'll develop type 2 diabetes, but there does seem to be a correlation between excess weight and the development of type 2 diabetes that SGLT-2 inhibitors could help improve.
The real game-changer for the SGLT-2 space came last summer when Eli Lilly (NYSE:LLY) and development partner Boehringer Ingelheim reported long-term cardiovascular data from the EMPA-REG OUTCOME trial for Jardiance. The study results showed that Jardiance led to a 38% reduction in cardiovascular death, a 35% reduction in hospitalization for heart failure, and a 32% drop in all-cause mortality. This was the first time ever that a diabetes drug delivered superior cardiovascular results relative to a current standard of care, which is especially important since about half of all type 2 diabetes deaths are caused by cardiovascular disease.
The big question surrounding Eli Lilly and Boehringer Ingelheim's study is whether this effect was specific to Jardiance or if this is a class effect. In other words, will other SGLT-2 drugs demonstrate similar superiority over a placebo in a long-term trial? We may soon have the answer.
This long-term trial could revolutionize type 2 diabetes treatment
A long-term study known as CANVAS, which is slated to end in February 2017 and befittingly involves Johnson & Johnson's (NYSE:JNJ) Invokana (the first SGLT-2 inhibitor approved in the United States) could be a game-changer of epic proportions for type 2 diabetics.
Invokana received the Food and Drug Administration's blessing for approval in 2013 and has exhibited the same side effects of weight loss and lowered systolic blood pressure that other patients taking SGLT-2 inhibitors have demonstrated in clinical trials. The key will be whether or not Invokana follows Jardiance's footsteps and leads to a superior reduction in major adverse cardiovascular events relative to a placebo. If Invokana does, the case becomes substantially stronger that SGLT-2 inhibitors may offer superiority over other classes of type 2 diabetes medicines, including Merck's Januvia.
Though Merck's management has stood by its assertion that DPP-4 inhibitors and SGLT-2 inhibitors are complementary medicines, Johnson & Johnson's study could completely change this "CANVAS" (pardon the pun).
In May, the U.K.'s National Institute for Health and Care Excellence (NICE) published its recommended final guidelines for patients with type 2 diabetes, and they strongly favored SGLT-2 inhibitors. NICE is the United Kingdom's version of the FDA in the United States.
Here's what the director of the NICE Centre for Health Technology Evaluation had to say:
For many people whose blood glucose levels aren't controlled by diet and exercise alone, metformin is the first drug treatment that they'll be offered. But some people may experience nausea and diarrhea, and they may not be able to take it if they have kidney damage. For people who can't take a sulfonylurea or pioglitazone, then the three drugs recommended in this guidance [Invokana, Forxiga, and Jardiance] can be considered. This is as an alternative to the separate group of drugs called dipeptidyl peptidase-4 (DPP-4) inhibitors.
The committee agreed that people with diabetes and their clinicians would value having an additional treatment option to help manage their type 2 diabetes -- which this positive guidance provides.
Although the FDA isn't bound to follow the recommendations of overseas drug regulators -- or even the recommendations of its own advisory panels -- I find it probable that the FDA will take NICE's praise of SGLT-2 inhibitors into consideration if Invokana also delivers superior cardiovascular results in CANVAS. It's possible that updated guidance from the FDA could recommend that physicians turn to SGLT-2 inhibitors in situations where metformin isn't enough to control their glycemic levels, instead of DPP-4s like Januvia.
Only time will tell what happens next, but we could be on the precipice of a major long-term shift in type 2 diabetes care.