Success of Wegovy, Ozempic comes with ‘huge responsibility’: Novo Nordisk executive VP

SINGAPORE – Blockbuster obesity drug Wegovy has been approved for use in Singapore since March 2023 by the Health Sciences Authority, but patients who may benefit from it will need to wait longer as the pharmaceutical firm behind it fixes its supply issues.

Novo Nordisk does not have a launch timeline yet for Singapore, but Mr Maziar Mike Doustdar, 53, the Zurich-based executive vice-president of international operations for the company, said there was “light at the end of the tunnel” to meet the high demand.

“We really need to make sure that we have a better situation with the supply and demand, especially for existing patients, before we introduce (Wegovy) to new markets,” said Mr Doustdar, speaking exclusively to The Straits Times when he was in Singapore in May.

In February 2024, the Danish drugmaker announced it was buying three manufacturing plants for US$11 billion (S$14.8 billion) to boost output of Wegovy.

Singapore is among the new markets waiting on Wegovy, which saw sales of the drug in the third quarter of 2023 up by 8.3 times, compared to the same quarter in 2022.

Novo Nordisk has also made headlines over another one of its products: Ozempic, which is used to improve blood sugar levels in adults with type 2 diabetes, along with diet and exercise.

Ozempic’s off-label use had gained global attention over the past few years, and in particular on social media as users documented its weight-loss effect.

The term “off-label use” means a drug is used for a medical condition or age group it is not approved to treat or administered in a different route or dosage than specified in the approved label. Ozempic’s popularity led to shortages, creating concern among diabetic patients who relied on it.

Both Wegovy and Ozempic are once-weekly injections that contain the same active ingredient, semaglutide. It mimics the actions of a hormone called glucagon-like peptide-1, or GLP-1, that is naturally released in the gastrointestinal tract in response to eating.

These so-called GLP-1 analogues causes various effects including slowing down the stomach emptying, acting on the brain to reduce appetite and boosting the release of insulin, which helps to regulate blood sugar levels.

These factors can lead to weight loss for those who take either Ozempic or Wegovy – the latter has a higher maximum dose of semaglutide.

Mr Doustdar acknowledged that Ozempic and Wegovy have achieved “huge brand recognition” and is moving into the league of brands like Aspirin and Kleenex – brand names of products that have become household names.

The popularity of both drugs has raked in profits for the company that got its start in 1923 producing insulin. The discovery of semaglutide in 2012 changed its trajectory.

As of May 2024, Novo Nordisk’s market capitalisation was at about US$600 billion. The pharmaceutical giant’s fortunes have given a boost to the Danish economy, and in 2023, it became Europe’s most valuable listed company.

Mr Doustdar said that with that level of popularity comes “a huge responsibility”, particularly now when there is supply-demand imbalance, to educate users on what each drug should be used for.

Ozempic and Wegovy have the same active ingredient semaglutide, but designated to treat different conditions. This is something users need to be educated about, especially with the supply-demand imbalance, said Mr Doustdar. PHOTO: REUTERS

“That sense of responsibility is important because there is a lot of noise – for lack of a better word – on social media and in the world. Sometimes it’s misunderstood,” he said.

“We want to make sure that that misunderstanding is not associated (with) Novo Nordisk, and if anything, (the company) helps clarify some of those things.”

The runaway success of how these semaglutide drugs have changed the conversation about how obesity is managed is not lost on Mr Doustdar. Not enough research and a belief that the obesity medication market was very small kept other pharmaceutical companies from exploring options for patients, he said.

Pointing out that Novo Nordisk was making “massive losses” on researching these drugs until a few years ago, Mr Doustdar said the company “raised (its) hand” and said that it saw obesity as a progressive chronic disease.

He said: “When we launched our first obesity product Saxenda in 2015, after 10 years of researching it, every other pharma company...laughed at us that we are going after nothing.

“Only after they saw the success of Novo Nordisk in the last few years, all of a sudden people started rushing to capture this so-called ‘gold market’,” added Mr Doustdar.

There was an unmet need, he added, coupled with misinformation about the cause of obesity and the underlying issues that it causes. Those who are overweight or obese may face increased risk of heart disease, diabetes, high blood pressure, high cholesterol, and liver disease, among other issues.

He said that obesity is a disease that does not need market resources to show how many people are afflicted with it.

“You just walk for five minutes outside and you can figure out how many people have it,” he added.

According to the World Health Organization (WHO), in 2022, one in eight people in the world were living with obesity. This is based on Body Mass Index (BMI), though it is generally accepted that the BMI cut-off points for defining overweight and obesity should be lower for Asians.

In Singapore, a BMI at 27.5 kg/m2 and above would mean a person is at high risk for weight-related health problems.

Figures from the 2021/2022 National Population Health Survey in Singapore showed that the crude prevalence of obesity is 11.6 per cent among residents aged 18 to 74 years in 2022. This was an increase from the 2019/2020 figure of 10.5 per cent.

Mr Doustdar said the way obesity is talked about hindered patients from getting help or medical treatment.

Patients with obesity often feel ashamed and are blamed for their condition even from a young age, being told it is their fault due to laziness or a lack of self-motivation – and that it is their own problem to fix.

In contrast, Mr Doustdar pointed out that diabetic patients are persistently encouraged by the medical community to manage their condition.

“Understanding the science of obesity, and how (an individual’s) different hormones interplay and interact with the environment to provide the best atmosphere to gain weight faster and keep (it on as compared to the individual’s) neighbour, who may not gain any weight in spite of the same environment, is really important.”

The “multifaceted” disease is much like having high blood pressure or high cholesterol, where long-term management is required, stressed Mr Doustdar.

Comparing it to people who have diabetes, he said: “We give you the part you’re not able to produce. Then your body’s happy, and you live long and happy.

“If we don’t give that to you, your body starts to go back to whatever it was producing and it’s still not enough. So then you get the same symptoms as you had before you were injecting insulin. It’s exactly the same with obesity,” explained Mr Doustdar.

Dr Tham Kwang Wei, senior consultant endocrinologist at Woodlands Health, told ST that when the weight loss target is attained – either for improving wellness, reducing health risks associated with obesity or treating underlying obesity-related complications – a patient may consider continuing the treatment to maintain weight loss.

The patient may also reduce the dosage to the lowest dosage needed to maintain the weight loss, as well as treat the obesity-related complications.

Ongoing changes in lifestyle will augment the weight maintenance and may be able to help one get off the medication, said Dr Tham, who is also the current president of the Singapore Association for the Study of Obesity.

She added: “When combined with lifestyle changes, the magnitude of weight loss of these medications is greater. As such, the use of any obesity medication should be coupled with lifestyle therapy which can further help maintain weight loss in the long run and minimise weight gain when the medication is stopped.”

With more obesity management drugs becoming available, Dr Tham noted that more people are coming forth to seek treatment through their healthcare professionals instead of struggling with the condition on their own.

However, the downside is that many do not see obesity as a chronic condition, and use these drugs as a quick fix, with the short-term in mind. These medications are then regarded as “fad drugs”, which aggravate matters and perpetuate such behaviours, she added

“With the availability of very effective obesity medications, it may mislead one to think there is no need to address lifestyle changes and the underlying root causes of obesity,” she explained.

“This can lead to the perpetuation of unhealthy lifestyle habits which can predispose one to weight regain and also ill-health, especially when the medication is stopped.”

While both drugs have been celebrated for their life-changing results, patients have reported side effects such as nausea, vomiting, constipation, and abdominal pain.

Mr Doustdar, however, said that both drugs are “incredibly safe”, having gone through clinical trials, and that side effects may arise from patients titrating the drug too fast. Titration of medicine means the dose is slowly increased in small amounts over time.

“We’re telling people… please follow the guidelines and the label. Don’t try to lose too much weight (too fast) on the first day by dialling (up the dose) much higher than it needs to be,” he said.

Director of the Obesity Centre and senior consultant at the department of endocrinology at Singapore General Hospital, Dr Lee Phong Ching, said that the side effects of semaglutide are “not uncommon, but can be mitigated by gradual dose escalation”.

He added: “Based on our experience with Ozempic, these side effects usually also improve with time. Just like how we treat other medical conditions, we weigh the risks versus benefits of our treatment, and we would stop or switch treatments if the risks outweigh the benefits.”

Given the potential benefits of semaglutide, the company is exploring new medical uses for it including treatments for Non-alcoholic Steatohepatitis (Nash), a condition in which the liver builds up excessive fat deposits.

Two trials are currently in various phases at three hospitals here. They are Singapore General Hospital, Changi General Hospital and National University Hospital, and are being conducted with semaglutide or a combination of it with another drug works with patients who have Nash.

Mr Doustdar said that with the introduction of some biomarkers as well as magnetic resonance imaging, it is now easier to diagnose patients with Nash, beyond waiting for a biopsy.

“We could actually come almost at the perfect time where people get diagnosed much earlier and faster, and then hopefully the product will show it can slow down the progression of Nash going from early stage to late stage.”

Novo Nordisk has already made headway with studying how semaglutide could play a part in the prevention of major adverse cardiovascular events.

Over a period of up to five years, Novo Nordisk’s Select trial tracked 17,604 non-diabetic overweight and obese patients, with pre-existing cardiovascular disease and no prior history of diabetes.

Those who took semaglutide 2.4 mg – the highest dosage in Wegovy – instead of a placebo, showed a 20 per cent reduction in major adverse cardiovascular events.

Another key finding: the results showed that weight loss continued over 65 weeks and was sustained for up to four years. They maintained an average of about 10 per cent weight loss after four years.

Mr Doustdar said: “I think the world has been very surprised by (semaglutide). We – with all the subjectivity that comes with it – think that this is borderline a miracle molecule because it can do so many good things to the human body.”

Beyond the clinical trials here, Novo Nordisk is optimistic about expanding its footprint in Singapore, where its regional office opened in 2022.

It moved a “good part of (its) operation” from Kuala Lumpur to Singapore to leverage talent and innovation here, said Mr Doustdar.

Singapore office is now a hub for several operations within Novo Nordisk, including being the regional office with supporting functions for its sales affiliates in South-east Asia, digital innovation and its sister company affiliate, Novo Nordisk Pharmatech.

Mr Doustdar, who has been with Novo Nordisk since he started as a 21-year-old office clerk, hopes that he will see a curative solution for type 1 diabetes in his lifetime. He said the company is experimenting with the ability to inject the body with external insulin-producing pancreatic beta-cells.

He envisions Novo Nordisk making this solution accessible to all, similar to a vaccine.

“The trick is to create that for the masses, so that this is not just experimental.. but we could really do it for the rich and poor everywhere,” he said.