Could multimodal pharmacotherapies help us defeat obesity?

In recent decades, obesity has become a global epidemic. Dr David Loczenski, Business Development Manager at Sygnature, tells how a new class of multimodal pharmacotherapy drugs may hold a solution…

According to the World Health Organisation, the prevalence of obesity has nearly tripled since 1975, with more than 1.9 billion adults now being overweight and 650 million of those obese. This staggering increase over the last 45 years has been catalysed by huge changes in how we eat, work and live – consuming more highly processed, energy dense foods, as well as living increasingly sedentary lifestyles.

Of course, while a certain amount of body fat is important for our health, storing too much fat can be extremely harmful over time. The human body is exquisitely fine-tuned to ensure that caloric intake and caloric output remain in close equilibrium (i.e. energy balance). However, even a small increase in daily caloric intake can lead to substantial weight gain over months and years in the absence of correspondingly increased output.

The real problem comes when excess fat is stored in and around our vital organs (such as our liver, pancreas, and heart), which can lead life-altering complications including type II diabetes, cardiovascular disease, and fatty liver disease.

Treating Obesity: A Challenging Mission

Lifestyle interventions (such as improved diet and exercise) are an effective means to reverse obesity, yet life-long adherence to such interventions is shockingly poor. A 9-year follow up study of nearly 300,000 participants showed that the probability of an obese individual (BMI 30-35) attaining a healthy body weight (BMI 18.5-25) was less than 1%. [1]

Yes, 1%.

So how can we help those who are suffering from obesity to achieve sustained weight loss? Currently, the only effective treatment for clinically obese individuals is making changes to the digestive tract though bariatric surgery – an extreme measure which is both invasive and dangerous (and ultimately still depends on lifestyle modifications for long-term success).

This leaves scientists with the challenging mission of developing pharmacological therapies as a non-invasive alternative, hoping to mimic both the weight loss and the beneficial metabolic health improvements associated with bariatric surgery.


A New Path: Multimodal Pharmacotherapies

Historically, pharmacological strategies to treat obesity have been unimodal in nature, acting on distinct physiological processes such as appetite or peripheral energy metabolism. But a new class of drug is making waves in the clinic; one that uses a multimodal approach (which is more akin to our natural physiology), coordinating a myriad of changes throughout the body.

These new candidate drugs have the power to simultaneously reduce appetite, increase energy expenditure, slow gastric emptying, and lower circulating blood sugar levels. Together, these effects act to collectively tip energy balance in favour of weight loss and to improve general metabolic health.

Hence, these new multimodal therapeutics present a thrilling advance towards developing a successful obesity treatment, and potentially improving the lives and health of millions across the globe.

At Sygnature we have been working to validate some of these new multimodal pharmacotherapies in our rodent models of obesity. Our findings agree with the impressive results being obtained in the clinic – these agents produce exceptional weight loss and improvements in metabolic health in our rodent models.

Putting to use our expertise in chronic weight loss studies, intricately detailed assessment of feeding/drinking behaviour, energy expenditure and physical activity, enables RenaSci to accurately determine efficacy as well as the mode of action of novel multimodal pharmacotherapies.

Alongside our obesity capabilities, we have an array of in-depth expertise in other metabolic conditions, such as insulin resistance, type II diabetes, non-alcoholic steatohepatitis (NASH) and kidney disease.

If you would like to know more about our in vivo models and multimodal research, we would love to hear from you. You can get in touch by using the contact form.

[1] Fildes, Alison, et al. “Probability of an obese person attaining normal body weight: cohort study using electronic health records.” American journal of public health 105.9 (2015): e54-e59.