Treating the whole patient to improve liver function
More than a billion people around the world suffer from cardiovascular, renal and metabolic (CRM) diseases, which are nearly always interconnected, centered on the heart, kidneys and liver and which can amplify one another.
This means their treatment calls for a holistic approach. But too often they are addressed piecemeal. Misdiagnosis is common, as are delays in treatment, and too few people have access to specialized medical care or the necessary medicines. As a result, they represent the leading cause of death globally, killing up to 20 million people each year.
Boehringer Ingelheim experts are targeting specific pathological mechanisms that directly address the interconnected nature of these diseases, which collectively represent the biggest public health crisis of our times.
Treatments for CRM diseases form the basis for some of Boehringer's most commercially successful products and remain a strong focus within its ambitious research and development pipeline.
Empagliflozin, sold under the brand name Jardiance®, is among the medications developed by Boehringer that now plays a growing part in treating CRM diseases. Its primary use to date has been as an antidiabetic, improving glucose control in people with type 2 diabetes.
Patients are responding to one of the most promising products in the pipeline, which can treat serious liver disease alongside obesity, presenting vast scope for addressing another area of unmet medical need.
Metabolic dysfunction-associated steatohepatitis, or MASH, is a form of liver inflammation, often due to the accumulation of fat, and is among the most widespread CRM illnesses. An estimated 34% of people living with obesity also have MASH. Boehringer's weight loss compound, Survodutide, which recently underwent successful stage 2 trials, is designed to mimic certain naturally occurring hormones that normally serve to reduce blood sugar levels and stimulate insulin production. It shows great promise as a way to improve liver function while reducing appetite in people with MASH.
“Time and time again, studies have shown that damage to just one of the body’s systems can progressively lead to damage in multiple organs," says Dr. Lykke Hinsch Gylvin, Chief Medical Officer and Head of Global Medicine at Boehringer Ingelheim. "By taking a holistic approach to treating these interconnected diseases, we can help protect patients' function of multiple organs. Through partnerships and collaboration with academia, the pharmaceutical sector plays a crucial role in developing these comprehensive treatments.”
“By taking a holistic approach to treating these interconnected diseases, we can help protect patients' function of multiple organs.”
Chief Medical Officer and Head of Global Medicine at Boehringer Ingelheim
Getting to grips with MASH
MASH is a progressive disease which causes inflammation of the liver, can lead to fibrosis, or scarring of the organ, and in later stages, cirrhosis, or long-term scarring leading to organ failure. Since the liver governs the body’s metabolism, it consequently plays a critical role in the cardiovascular, renal and metabolic system. MASH affects more than 115 million people worldwide and the number of such cases is expected to increase by 63% between 2015 and 2030.
Besides being tied to obesity and acting as a precursor to cirrhosis, MASH is also linked to diabetes, hypertension and heart disease. None of these ailments can be isolated from one another, and it is necessary to consider the whole patient in devising an effective care strategy.
MASH, formerly known as non-alcoholic steatohepatitis, is a serious health threat that requires more attention. If you are not familiar with the new term, you probably should be, both because you probably know someone whose quality of life, relationships and ability to work are deeply affected by it and because of the significant financial burden it single-handedly puts on healthcare systems. By the end of the decade, it will be the fastest growing cause for liver transplantation in Western countries.
The Phase II trial of Survodutide announced in early 2024 showed groundbreaking results with up to 83% of adults treated achieving a statistically significant improvement in MASH, with significant reductions in fibrosis during a 48 week treatment versus placebo. The compound has the potential to increase energy expenditure and has a direct impact on liver function which potentially contributes to the improvements in fibrosis. It also led to decreases in appetite while increasing fullness and satiety.
“These data position Survodutide as a potential leading treatment for a population with great unmet medical needs, and will bring hope to people living with MASH and with fibrosis,” said Dr. Arun Sanyal, M.D., Professor of Medicine, Physiology and Molecular Pathology at Virginia Commonwealth University School of Medicine, and Principal Investigator of the trial.
“These data position Survodutide as a potential leading treatment for a population with great unmet medical needs, and will bring hope to people living with MASH and with fibrosis.”
Dr. Arun Sanyal, M.D., Professor of Medicine, Physiology and Molecular Pathology at Virginia Commonwealth University School of Medicine
A holistic approach to the management of cardiovascular, renal and metabolic conditions such as heart failure, chronic kidney disease and type 2 diabetes is needed
Cardiovascular, renal and metabolic conditions often present no symptoms in the early stages, so many go undiagnosed
Coexistence of two or more cardiovascular, renal and metabolic conditions is associated with increased mortality1,2,3
Early screening, diagnosis and intervention can delay the consequences of heart failure, chronic kidney disease and type 2 diabetes, including cardiovascular death4,5,6
Survodutide is the first product to show this level of benefit in a Phase II MASH trial.
As Survodutide moves into Phase III trials, it continues to represent a great hope for patients with MASH and related disorders, dramatically expanding the treatment landscape for these interrelated diseases. Moreover, its statistically significant results in contending with MASH suggest the potential to lead to clinically meaningful benefits across the CRM spectrum, providing treatment for the more than 1 billion people affected by these interconnected diseases.
By targeting specific pathological mechanisms that directly address the interconnected nature of CRM diseases, Boehringer Ingelheim has built up a strong pipeline of innovative medicines which the company is confident can expand the range of available treatments to make life better for millions of people in the coming years.
Explore why we need a patient-centric approach to CardioMetabolic disease research and development
References
Diabetic eye diseases
- Diabetic retinopathy is the leading cause of vision loss in adults8
- One-third of patients with type 2 diabetes have diabetic retinopathy8
Type 2 diabetes
- Affects 425 million people worldwide8
- 1 in 10 adults estimated to have diabetes by 20408
- Complications include increased incidence of stroke and heart attack, kidney disease, diabetic retinopathy, liver disease 8,9
- More than half of patients with type 2 diabetes are obese10
Diabetic kidney disease
- Diabetes, hypertension and kidney disease are highly interlinked
- Up to 40% patients with type 2 diabetes will develop chronic kidney disease8
MASH
- Global prevalence of non-alcoholic fatty liver disease (MASLD) is currently estimated to be 24%11
- Both MASLD and the more serious form non-alcoholic steatohepatitis (MASH) are highly prevalent among patients with type 2 diabetes
- MASH is expected to become the most common cause of advanced liver disorders, eventually necessitating liver transplantation, in the coming decades
Overweight & obesity
- Worldwide obesity has nearly tripled since 19757
- In 2016, nearly 2 billion adults7 worldwide were overweight or obese.
- About 13% of the world’s adult population were obese in 20167
