Research-led results for interconnected complex diseases

Cardiac, renal and metabolic diseases can have complex interdependencies. A patient’s gender can affect the way the symptoms manifest themselves – while also playing a role in diagnosis. Boehringer Ingelheim continues to drive research into these relationships and potentially new therapeutic uses for its drug Jardiance.

For much of her early life, Pamela Thomas’s congenital heart defect didn’t really bother her. She worked, exercised and led a generally normal life. But at age 38, she began experiencing chest pains, her feet started to retain water, and she even fainted a few times.

“These serious symptoms scared me,” Ms. Thomas recalls. Her doctor sought to calm her, saying that the fainting wasn’t necessarily a worry and that her feet were probably swollen because there was too much salt in her diet. “I didn’t feel like I was taken seriously and was completely unsettled,” Ms. Thomas says.

Within two weeks, her body had retained so much fluid that she had gained a noticeable amount of weight. A cardiologist ordered her rushed by ambulance to a hospital — where 1.7 liters of water were drained from her chest. “When I woke up from the sedation, I felt free,” says Thomas.

Fourteen years and several cardiac surgeries later, Ms. Thomas has her heart problems under control. She is now active in, an advocacy group for women with heart disease.

People like Ms. Thomas are a reason that Boehringer Ingelheim is a long-time leader in global research involving heart disease and related conditions in order to develop effective therapies. That includes a series of clinical trials tracing to 2016, a program called EMPOWER, in collaboration with Eli Lilly.

Interdependent diseases

Ms. Thomas’s health history shows how difficult it can be to identify complex conditions at an early stage and treat them properly. Her story also indicates that women, in particular, are often misdiagnosed.

Research has shown that heart failure takes longer to be detected in women than in men and that misdiagnosis occurs twice as often. And because the risk of women suffering depression as a result of the diagnosis is 50 percent higher, effectively managing such conditions is crucial to mental health.

Gender aside, there are many reasons for elusive diagnoses. Symptoms such as shortness of breath or impaired performance don’t necessarily point toward heart problems. Furthermore, cardiac insufficiency is often related to other diseases, particularly type 2 diabetes.

Type 2 diabetes, a metabolic disease, has a far-reaching impact. Too much sugar in the blood can lead to fatty deposits in blood vessels and narrowing of arteries. The narrower the coronary arteries, the less oxygen received throughout the body and the greater the risk of a heart attack. Fatty deposits can also build up in the hearts of diabetes patients, further harming the vital organ.

Diabetes, moreover, can also harm the kidneys — whose crucial job it is to filter harmful substances and excrete them from the body through the urine. Too much sugar in the blood, or circulation problems, can impair the function of the kidneys.

There are links between diabetes and diseases of the heart and kidney. Boehringer Ingelheim and Eli Lilly’s EMPOWER studies will continue to research their interdependencies.

A promising therapy

Researchers at Boehringer Ingelheim continue to investigate the interdependencies of heart and kidney disease and type 2 diabetes in order to develop effective therapies. Jardiance (empagliflozin) is a promising medicine in this regard.

The SGLT-2 inhibitors in Jardiance were originally used to treat diabetes. Later, Boehringer Ingelheim’s and Eli Lilly’s EMPEROR studies revealed that they also help people with a reduced cardiac ejection fraction — when the heart isn’t pumping out enough blood. It has also recently been shown that they can also help people with preserved ejection fraction — when the heart doesn’t fill with enough blood.

The medicine works regardless of whether the patients suffer from diabetes. New studies show that empagliflozin can also help with certain renal disorders, even if the patients do not suffer from diabetes (See infobox).

The need to overcome gender bias

The importance of a holistic medical approach is illustrated by Ms. Thomas’s case, because gender can also play a role if a disease is to be properly treated. And too often, experts say, women are not given accurate diagnoses or sufficient treatments.

Martha Gulati, President of the American Society for Preventive Cardiology, points out that drugs are predominantly tested on men. “Women are still underrepresented in clinical studies,’’ Dr. Gulati says. “This is particularly true for heart failure.”

And so, according to Dr. Gulati, study results do not sufficiently reflect the biological differences between genders. For example, women’s hearts have a naturally higher ejection fraction than men’s. As a result, the ejection fraction of a woman with heart problems could appear normal even though it is actually too low.

Gender differences also impact the relationship between type 2 diabetes and heart conditions, with diabetes more often leading to heart disease in women than men, Dr. Gulati says. Ultimately, heart failure is equally debilitating to women and men — even if the risk factors differ.

For Boehringer Ingelheim, the interrelationships of these diseases and the need to eliminate gender biases in clinical trials, are major impetuses as the company continues to pursue — and improve — research on the causes and interdependencies of complex medical conditions.

Groundbreaking research continues

Boehringer Ingelheim’s and Eli Lilly’s EMPOWER studies are continuing to research the interdependencies of diabetes, heart disease and kidney problems. More than 400,000 adults have been included in the clinical trials to date, which study the therapeutic use of Jardiance (empagliflozin) — a SGLT-2 inhibitor originally used to treat diabetes that has shown to be effective more broadly.

In 2021, EMPEROR — a study that is part of the EMPOWER program — showed that Jardiance greatly reduces the risk of hospitalization for patients suffering from heart failure. Whether the patients suffered from type 2 diabetes did not play a role. The positive effect was visible in people with preserved and reduced cardiac ejection fraction.

A follow-up study, EMPA-KIDNEY, led to such promising results that it was concluded ahead of schedule. Detailed results were publicly presented in November 2022. 6,600 people with various renal ailments took part in the EMPA-KIDNEY study, which included patients with and without diabetes. The study showed significant benefits of Jardiance in reducing kidney disease progression, or cardiovascular death, by 28 percent vs. placebo in people with chronic kidney disease.

Nearly 850 million people worldwide live with a renal disease. Many of them rely on dialysis, which has a considerable impact on their daily lives. Chronic kidney diseases are also a frequent cause of death: worldwide, between five and ten million people die from such diseases every year. These EMPA-KIDNEY results promise a better life for millions of people who suffer from renal disorders