Beyond the Semaglutide Shortage: Emerging News About GLP-1 Receptors

The widespread patient demand for semaglutide (Ozempic®) has created unprecedented challenges for GPs. Weight loss specialist Mr Jason Winnett looks at the latest evidence.

What is the current compounding ban on semaglutide? How were GPs involved?

Following a Four Corners investigation in April 2024, compounding chemists will be banned from producing and selling the GLP-1 receptor agonist semaglutide by October 2024.

The proposed ban was recently announced by Federal Health Minister Mark Butler, and follows the Four Corners investigation which found unlawfully manufactured replica semaglutide drugs were produced and illegally shipped overseas.

GPs had been bombarded with faxes from multiple pharmacies promising compounded versions in the middle of unprecedented global shortages. It was only after an eagle-eyed GP began noticing odd symptoms in patients such as peripheral neuropathy, that he warned his patients to stop taking the drugs and reported the issue to the TGA.

Semaglutide, currently approved for Type II diabetes in Australia, is still currently in huge demand off-label for weight loss – both in Australia and around the world. The Four Corners investigation found that the drugs, unlawfully compounded in a backroom pharmacy, caused neuropathic side effects due to elevated levels of Vitamin B 12 and L-Carnitine.

How effective is semaglutide?

The potency of semaglutide was confirmed in a landmark 2021 New England Journal of Medicine, which found it resulted in 14.9% weight loss compared to 2.4% placebo in 1961 subjects over 68 weeks.

A third of semaglutide group patients lost 20% of weight. Furthermore, 84%of patients with pre-diabetes returned to normoglycemia, compared with 47.8% in placebo.

Weight circumference in the Semaglutide group was -13.4cm, compared with -2.4cm in placebo.

There was no difference between benign and malignant neoplasms, and one death in each group.

The dosing was the strength of Wegovy (2.4mg), not yet in Australia, which is a stronger concentration of Ozempic (0.5-1mg for weight loss, and up to 2mg for diabetes).

In May 2024, as second study in the New England Journal of Medicine, found that the risk of a primary heart or kidney event was 24% lower in the semaglutide group. This study followed 3533 participants with Type II diabetes for 3.4 years.

What are the downsides and risks associated with Semaglutide?

In the first NEJM study there was a higher risk of pancreatic inflammation in the semaglutide group (2% v 1.2% placebo for gallstones) however all recovered.

Serious side effects were mostly gastrointestinal (9.8% in control group v 6.4%in placebo). Common side effects included diarrhoea, and nausea.

Regain weight remains an issue and tends to pile straight back on after patients stop taking the medication according to one study of 1961 patients in the Diabetes, Obesity and Metabolism journal.

“Semaglutide is not a ‘magic pill’ and not without its downsides,” says Mr Winnett.

In recent times it has also been linked gastroparesis, resulting in 87 lawsuits currently in the US. Lawyers for plaintiffs had argued that the manufacturer Novo Nordisk had not initially warned patients of the risk.

A recent study in JAMA of 4144 patients also found an elevated risk of gastroparesis and adverse gastrointestinal events with GLP-1 agonists.

“Gastroparesis disrupts regular, spontaneous muscle movements in the stomach,” says Mr Winnett. “This prevents proper stomach emptying and can be very uncomfortable and cause symptoms of feeling full, vomiting, weight loss, tummy pain and bloating. It tends to be a chronic, painful and permanent disease.”

“Despite it being rare, patients and doctors should be acutely aware of the side-effects involved.”

As a clinician, how should I manage medication-induced gastroparesis?

“Many semaglutide patients experience mild GI symptoms and learn to manage them with smaller meals, avoiding foods with high fat and avoiding meals late at night before bed,” says Mr Winnett.

“Staying hydrated and anti-nausea medication can also reduce these issues.”

“However, the ability to tolerate the medication is important too. GPs should monitor this and always ask if the patient has significant vomiting, diarrhoea, constipation, heartburn, fatigue, difficulty swallowing, bloating, satiety, weight loss or issues with stomach pain.”

“Type 2 Diabetes, viral illness, pancreatitis, gallbladder disease and kidney disease should be considered as causes of these symptoms too. However, if symptoms are severe or do not improve despite dietary modifications and smaller meals after two weeks, the drug should be stopped. The patient should also be reviewed by a bariatric physician, a bariatric surgeon or a gastroenterologist promptly.”

When and to whom should I prescribe Semaglutide?

Increasingly, doctors are facing pressure from overweight and obese patients who claim they are being stigmatised or vilified for asking for a prescription. Why should obesity be any less valid to treat than diabetes these patients ask?

On the other hand, disheartened diabetes patients remain at risk of worsened glycaemic control and new complications if they do not receive Ozempic®.

“As doctors, we need to work together on the issue until this shortage is resolved,” says Mr Winnett.

What should I do if I cannot prescribe Semaglutide for my obese patients?

Pharmacotherapy alternatives such as liraglutide can help, though they are slightly less effective for weight loss.Contraindications include medullary thyroid cancer and multiple endocrine neoplasia 2 (the same for Wegovy® and Ozempic®). I use the following medications much more sparingly:

Phentermine is tolerable in the short term but it can often cause dry mouth, palpitations, hypertension, and insomnia. Some patients report better results by varying the dose and skipping a couple of days, due to drug tolerance issues. Many patients use 15 mg on alternate days, or 30mg weekdays only.

Topiramate is traditionally used for migraines and tension headaches but also suppresses appetite. It can be taken at a dose of 25-50 mg daily or twice daily. Side effects include mood swings, blurred vision, and suicidal thoughts.

The combination of naltrexone and bupropion targets brain appetite but is linked to hypertension, seizures, constipation, and suicidal thoughts.

What should I do if I cannot prescribe Semaglutide for my obese patients?

“If we focus on the first NEJM Semaglutide study, a third of semaglutide group patients lost 20% of weight, which is improving with newer generations of medications, and there will be much development in this space,” says Mr Winnett.

However, surgery is certainly often a better long-term option for patients who do not want the expense or side-effect protocol of ongoing medications.

While about 15-35% of surgical patients did not reach their goal weight loss, typically due to factors such as advanced age, previous abdominal surgery, hypertension, or depression, the majority succeeded, according to a 2020 study in the BMC Endocrine Disorders Journal that followed 130 patients for a year after surgery.

Another meta-analysis of 20 bariatric surgery studies in 2023, found that “remarkably even in the long-term analysis, weight reduction remained relatively preserved,” especially with SG and RYGB.

How Winnett Specialist Group Can Help

“At the Winnett Specialist Group we perform many bariatric surgeries including the Orbera® Intragastric Balloon, the Adjustable Gastric Band,

Sleeve Surgery and Roux-en-Y Gastric Bypass,” says Mr Winnett.

“We are also well versed in prescribing weight loss medications to obese and diabetes patients and our comprehensive team includes a bariatric physician, exercise and lifestyle consultant, dietitian and psychologist support.”

We pride ourselves on the “right surgery” for the right patient” as well as rigorous assessment, medication support and follow-up. For more information on bariatric surgery and weight loss support, visit our insights section or contact us directly. We’re here to share our knowledge with fellow health professionals and work together to enhance patient care. Reach out to us, and let’s improve patient outcomes together.

Disclaimer * This article is for educational purposes only. Mr Jason Winnett has no financial arrangements or clinical trial arrangements with any pharmaceutical companies that manufacture the above weight loss medications.