If Ozempic were a professional athlete, their first few seasons would be among the most illustrious in sports history. As a brand-new medication, this rookie superstar blasted onto the scene to immediate acclaim across virtually every media channel, not only for its efficacy in treating type 2 diabetes but also for its apparent utility as an off-label weight-loss aid.

Not long thereafter, semaglutide (the active ingredient in Ozempic) would receive formal FDA approval for treating obesity under the brand name Wegovy. This accomplishment only further propelled Ozempic and its sister medications (Wegovy and Rybelsus, all of which contain semaglutide) securely into stardom amongst the general population.

More recently, as though Ozempic had not already padded its CV sufficiently, studies have emerged showing that semaglutide may be an effective treatment for congestive heart failure – a deadly and increasingly common illness in America. These studies may represent the start of Ozempic’s path toward becoming one of the most – if not the most – effective heart failure medications presently available.

Heart Failure

The term “heart failure” bluntly describes the catastrophic condition in which the heart, which is vitally important to every other organ in the body, loses the ability to properly circulate blood throughout the circulatory system.

The heart, being a complex piece of biological machinery, can fail in a variety of complex ways. The ventricles (or chambers) of the heart can lose their ability to contract or relax normally, leading to a reduction in the amount of blood that is ejected with each beat (called “reduced ejection fraction”) or to the amount of blood that returns to fill the chamber after each beat (called “preserved ejection fraction”). Often, heart failure begins in the left ventricle, which can have knock-on effects to the right ventricle, as the reduced pumping power causes a build-up of fluid pressure that harms the right side of the heart.

Congestive heart failure (“CHF”) is a particularly urgent form of the disease. Often requiring urgent medical care, CHF occurs when the reduced pumping ability of the heart causes blood to build up in the veins that bring blood from around the body back to the heart. The resulting increase in pressure often leads to fluid retention, or edema, particularly in the lower extremities. When such edema occurs in critical organs like the lungs and kidneys, the body’s ability to perform basic functions like breathing and sodium removal can be severely impaired.

The severe complications that can stem from congestive heart failure are often fatal, but can also lead to fatigue, shortness of breath, and a sharply reduced capacity for exertion. Unfortunately, CHF accounts for over 50% of heart failure incidences in the U.S., and occurrences continue to increase.

Causes of heart failure are complex, but the condition is closely linked to obesity. CHF is thought to occur due to the narrowing of cardiac arteries and elevated blood pressure levels, both of which are known to be consequences of obesity and poor diet. Estimates suggest that obesity and its complications are responsible for 11 – 14% of heart failure cases, and 80% of patients with CHF are obese or overweight. Unfortunately, obesity is also on the rise across all demographics, which will likely continue to contribute to increase CHF incidences over time.

Trends in Heart Failure

Congestive heart failure represents a real and escalating public health danger to the U.S. population. Some estimates suggest that 6.2 million Americans currently suffer from heart failure, and that the disease represents the leading cause for admittance to a hospital in patients over the age of 65.

As bleak as those numbers seem already, some data appear to show that the problem is only worsening. Heart failure not only appears to affect increasing proportions of the general population but is also becoming more common amongst segments of the population once seen as being at lower risk. One retrospective analysis, for example, demonstrated a statistically significant increase in heart failure among young adults since 2012, whereas heart failure had typically been associated as a condition for patients 45 and over. That study provided a contrast to pre-2012 data, showing that heart failure mortality rates among young adults had previously been relatively stable. And, according to another study published in the American Journal of Medicine, rates of heart failure across every age category increased significantly between 1999 and 2016. The authors of that study noted that “a substantial proportion of US adults are at high 10-year heart failure risk”.

Recent Research

Novo Nordisk’s initial claims

The increasing health burden posed by heart failure has led researchers to assess novel forms of possible treatment. Novo Nordisk, the manufacturer of Wegovy, Ozempic, and Rybelsus, has been no exception; the company released research data in August from a groundbreaking SELECT trial that assessed the effects of Wegovy in non-diabetic middle-aged patients with obesity and heart disease. Their results gathered over a five-year period and from over 17,000 patients, indicated that Wegovy usage was associated with a 20% decrease in the incidence of major adverse cardiovascular effects. Given that semaglutide medications like Wegovy are only approved for type 2 diabetes and/or weight loss at present, the findings that semaglutide medications may have broader utility in the cardiovascular health arena was a welcomed surprise.

Expanding on Novo Nordisk’s data

More recently, renowned cardiovascular researcher and physician Mikhail Kosibrod, as well as several co-authors, conducted further research into Wegovy’s potential in treating heart failure. The team of researchers recently published their findings in the prestigious New England Journal of Medicine and presented the findings at the annual meeting of the European Society of Cardiology – the world’s foremost conference on cardiac health. The results were met with acclaim throughout the cardiac health community.

Kosibrod et al. split a population of preserved ejection fraction heart failure patients into two groups – those who would receive regular injections of semaglutide, and those who would receive only a placebo – and compared a variety of outcomes between groups after a period of time. Their results, though not necessarily conclusive, were staggering.

The study used a variety of metrics that typically show impairment in heart failure patients to measure outcomes. They looked at differences in walking ability, shortness of breath, capacity for exertion, overall body weight, inflammation, and various other symptoms. Amazingly, the treatment group (those who received semaglutide) outpaced their placebo counterparts in nearly every measured metric by the conclusion of the study.

Results of the Kosibrod study

Patients who received semaglutide increased the distance they were able to walk in six minutes by 21.5 metres, compared to only a 1.2 metre increase for the placebo group. They also reduced their body mass by an average of 13.3%, compared to only 2.6%. Perhaps most significantly, a questionnaire used to assess global cardiovascular function in heart failure patients (the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, or KCCQ-CSS) revealed that the semaglutide group showed two-fold improvements in CSS scores relative to the placebo group. Given that the KCCQ-CSS accounts for a range of symptoms and physical limitations associated with heart failure, such a profound improvement in scores is very telling of the profound and broad effects the treatment had on heart failure-related complications.

Adverse effects observed

A thorough pharmaceutical study will look for negative effects as well as positive ones, and the Kosibrod study was no exception. The researchers reported that there were relatively few safety incidences associated with the treatment, even noting that the treatment group had fewer negative safety outcomes than the placebo group. This incredible result addresses the important question of whether semaglutide usage is safe for heart failure populations, though it is also important not to draw premature conclusions about a drug’s safety for any indication without further clinical trials.

It should also be noted that some treatment subjects were discontinued from the study, though primarily due to intolerance of gastrointestinal distress that is not uncommon with semaglutide use.

Implications of Recent Findings

Heart failure has been historically difficult to treat. Physicians have had relatively few effective therapies in their arsenal, and those that were available often left a lot to be desired.

The relative absence of effective treatment options for heart failure is provides important context to the hype and acclaim recent research into Wegovy has received. Experts in the field have called these study results “transformational”, alluding to the possibility that doctors may soon be able to resort to far more effective treatments in their heart failure patients. These results could not be timelier, either; with heart failure rates on the rise across the country (and many parts of the world), there is a desperate need for a change in strategy when it comes to treating the condition effectively.

Until now, doctors treating failure have been limited to only a few medications with the potential for modest benefits in patient outcomes. Diuretics and water pills have been a staple in this regard, as they cause the body to pass some of the retained fluid through increased urination. Another option has been SGLT2 inhibitors, primarily used as an antidiabetic medication, which can cause some alleviation of symptoms and a reduction in hospitalizations. Still, both of these options are relatively inadequate in addressing the long-term health outcomes of heart failure and have struggled to meet the monumental task of systemically addressing heart failure.

In contrast, Wegovy has been described by Kosibrod as yielding the largest improvements ever seen with any pharmacologic intervention for heart failure to date, yielding benefits with the largest magnitude “ever seen with any agent in [preserved ejection fraction heart failure]. Wegovy’s success here may be owed to its tendency to treat obesity, which is known to have strong correlations, and perhaps strong causal links, to heart failure. If further trials continue to show success, Wegovy may ultimately contribute to a paradigm shift in heart failure treatment, where obesity is treated as an underlying cause of heart failure, not merely as a n incidental co-morbidity. It may also be true that Wegovy attacks heart failure from other angles, such as by reducing inflammation and reducing fluid collection and congestion.

Study Limitations

An important clarification to make is that these study results, despite their promise, are not equivalent to a full range of clinical trials and FDA approval. In other words, we should be cautious in making overly firm conclusions from these data. The fact is that further studies will be needed to concretely assess the viability of Wegovy as a primary treatment for heart failure.

For instance, this study was criticized by some as being limited in its demographic scope. Nearly every one of the patients involved was white, and patients from different ethnic backgrounds have been known to experience variable outcomes across a range of illnesses and treatments. Further research will need to expand the diversity of its test populations before being able to draw any generalized conclusions about the treatment’s efficacy. Fortunately, a new and more inclusive study looking at semaglutide in heart failure patients from a diverse range of ethnic backgrounds should be publishing soon, which could help expand scientific insight into the drug’s effects across a more representative population sample.

Conclusion

Sufferers of major health disorders like heart failure can feel hopeless in a medical context which has little to offer in the way of effective treatment options. Stories like these, which details important and promising breakthroughs in medical science offer important hope for such individuals and the professionals who treat them. However, it’s important to take such news with moderation until more conclusive determinations about a drug’s potential role in treatment are reached.

Still, it seems safe to conclude that semaglutide medications are not yet fully understood and may hold far more promise than their current indications suggest. It may be true that in a few short years, heart failure, like diabetes and obesity, is added to the repertoire of conditions that Wegovy can treat with relative safety and significant reliability.