What Do the Jardiance Results Mean for You? Why We Need Patients to Stay Enrolled in Trials

Twitter summary: Kelly Close on why continuing participation in long-term CVOTs is so necessary. 

Here at diaTribe, our heads are still reeling from the magnitude of the results from the EMPA-REG OUTCOME study presented in Stockholm last week at EASD 2015, the largest European diabetes meeting of the year. This study found that Jardiance (aka empagliflozin, an SGLT-2 inhibitor) led to the following risk reductions in people with type 2 diabetes at high-risk for heart problems:

• 14% reduction in total cardiovascular (CV) events – including heart attacks, strokes, and heart-related deaths

• 38% reduction in risk of heart-related death

• 32% reduction in risk of total mortality (from all causes)

• 35% reduction in hospitalizations for heart failure

Such a dramatic benefit was not expected, and we’re still trying to understand the implications of these results. This is the first modern diabetes drug to show a significant decrease in cardiovascular risk in a cardiovascular outcomes trial (CVOT) – these trials have caused some controversy ever since the FDA mandated them in 2008, as they are very expensive and until now have shown entirely neutral results.

Jardiance is not the only SGLT-2 drug with a major CVOT – both of the other FDA-approved SGLT-2 inhibitor drugs, Invokana and Farxiga, are currently being tested in trials. These include CANVAS and CANVAS-R, expected to report in 2017, DECLARE-TIMI58, expected to report in 2018, and CREDENCE, which is still recruiting. With the EMPA-REG results unveiled, some people in these other CVOTs may be tempted to drop out of their trials in case they are in the placebo control arm (and therefore not receiving the drug being tested), so that they can start taking Jardiance right away. While this initial reaction is understandable, it’s crucial that patients realize that all the other CVOTs need to continue at full speed, and that means that we need all enrolled patients to stay enrolled. The EMPA-REG OUTCOME results won’t mean nearly as much if they can’t be replicated, and there’s still so much to know about SGLT-2s and other diabetes drugs that have the potential to improve millions of lives.

What Does This Mean For People In Other Long-Term CVOTs?

If you are one of the thousands of patients enrolled in one of the other ongoing long-term cardiovascular outcomes trials for SGLT-2 inhibitors, thank you! This is immensely important research that will help shape public health policy over the coming decades. If the findings for all the trials are positive, that would be huge news with the potential to change the standard of care – and the life expectancy – for people with diabetes. And if the findings are neutral, they will still provide valuable information about the safety of SGLT-2 inhibitors for patients at high cardiovascular risk, the differences between the various drugs in the class, and in some cases (CANVAS-R and CREDENCE) the drug’s effects on kidney disease.

There are still SO many unknowns not only with this study but also to the field in general, and they can only be answered by more studies. One study’s positive results aren’t enough to change the standard of care, and more research is needed to determine whether these benefits apply only to Jardiance or to the entire class of SGLT-2 inhibitors. Here are just a few of the many questions that we have about SGLT-2 inhibitors following the EMPA-REG OUTCOME results:

• What is the mechanism by which Jardiance decreased risk of cardiovascular death and hospitalization for heart failure? The researchers behind this study don’t fully understand yet – we need more completed CVOTs to help us answer this!

• Do SGLT-2 inhibitors (and other diabetes drugs) improve overall heart health by reducing nonfatal heart attacks and strokes? Jardiance demonstrated a decrease in risk of fatal cardiovascular events, which is of course very meaningful, but understanding more about the effects of diabetes drugs on nonfatal heart attack and stroke risks is also important.

• Is the heart-protective factor replicable in other ongoing trials? The DECLARE-TIMI58 trial has more than twice as many participants as EMPA-REG OUTCOME – this means that there will be an even greater opportunity to observe the number of deadly cardiovascular events prevented if SGLT-2 inhibitors are in fact heart-protective across the board. If different SGLT-2 inhibitors have different effects on outcomes, that will also be important for patients and doctors to know.

Overall, it is important for people to participate in research trials – Dr. David Wendler, the Head of Research Ethics at the National Institute of Health (NIH), gave a valuable presentation earlier this summer at Friends For Life where he convincingly argued that participating in research has many personal benefits. Contrary to what some might initially believe, people in research studies often receive better care than those who receive standard clinical care since the researchers have so much experience with the specific condition they are studying. Additionally, in the same way that volunteering for a charity can be emotionally beneficial, participating in research can be an opportunity to help others, resulting in a “more valuable, meaningful, and interesting life.” Sign me up!

This is such an exciting time – I know I’m not alone when I say that I never thought the day would come that a CVOT for a diabetes drug would show such impressive heart-protective effects. Let’s keep the momentum going and continue pushing forward with all the other long-term CVOTs that so many people are enrolled in. 

Getting Involved In Clinical Research

If you aren’t already participating in research, I highly encourage you to look for trials in your area that can potentially improve your own health while you contribute to scientific knowledge regarding diabetes. I invite you to check out the following resources…

• Talk to your doctor or diabetes educator to find out whether she or he knows of any ongoing trials you can participate in. 

• Trial watch on the diaTribe website makes it easier to understand clinical trials listed on government websites, making it clear what the trial is testing, why it’s important, its length, location, and more.

• TrialReach is a new initiative to make it easier to search for trials near one’s home that they might qualify for and benefit from.

• Registries and databases such as clinicaltrials.gov, NIH, and Diabetes Trial Net are all filled with research opportunities for people with type 1 and type 2 diabetes – these registries are often hard to navigate, but if you use “Advanced Search” you can narrow down the results to meet your needs.

I'd love to hear your thoughts!

very best,

Kelly L. Close