OZEMPIC – A STORY OF SOCIAL MEDIA vs SCIENCE

Dr Angela Murphy writes:

The twin pandemics of obesity and Type 2 diabetes have created a need to find an effective treatment for both chronic diseases. Yes, obesity is also a chronic disease.

A disease is a disordered condition in the body – in diabetes it is abnormal sugar levels; in obesity it is a body weight that is above the normal range. Chronic implies long-standing; maybe even lifelong.

A healthy lifestyle is essential. No medication will override a poor diet or lack of exercise. However, for many people living with diabetes, medications are needed to control blood glucose levels. Most people living with Type 2 diabetes are overweight or obese so any diabetes treatment needs to assist in managing this condition too.

Definition of obesity:

Obesity – body mass index (BMI) which is calculated by dividing height squared into weight:
> 30kg/m2 = obese
25-30kg/m2 is overweight
It is important to measure waist circumference in patients to ascertain the degree of visceral fat.  It is this fat which causes most of the metabolic complications of – especially diabetes.

The incretin hormones

When food enters the small bowel it causes the release of glucagon-like peptide 1 (GLP-1) and glucoinhibitory peptide (GIP) – the incretin hormones. They stimulate the pancreas to make insulin to control blood glucose at mealtimes. The action of incretins has been found to be reduced in Type 2 diabetes, so medications were developed to improved incretin hormone levels. The medications produced to increase GLP-1 levels (called GLP1-receptor agonists)  have made a significant impact on the treatment of both diabetes and obesity. They do this by:

1. Stimulating the pancreas to increase insulin.
2. Blocking the liver from producing glucose
3. Directly inhibiting the appetite centre in the brain
4. Decreasing how quickly the stomach empties which means a person feels full for longer.

In addition, some of the GLP-1 medications have been shown to protect the heart.

The GLP-1 receptor agonist medications

Most GLP-1 receptor agonists are given as a subcutaneous injection as they are rapidly destroyed in stomach acid. However, oral forms are now available overseas. The GLP-1 receptor agonists registered in South Africa for diabetes are:

GLP-1	HOW TO TAKE	DOSE	EFFECT ON GLUCOSE	EFFECT ON WEIGHT
BYETTA (exenatide)	Twice daily within 60 min of breakfast and dinner	Start with 5ug for a month; then 10ug	Effective	3-4kg loss
VICTOZA (liraglutide)	Once daily at same time	Start at 0.6mg and increase to 1.2mg and even 1.8mg	Good	5-10% loss
TRULICITY(Dulaglutide)	Weekly in single use pen	1.5mg fixed dose	Good	Average 3kg loss
OZEMPIC (Semaglutide)	Weekly	0.25mg for first month; then 0.5mg and if needed 1mg	Good	10-15% loss

GLP-1 receptor agonists not available in South Africa:

• Rybelsus (semaglutide) – this is the only oral GLP-1 receptor agonist available as a daily pill either in a 7mg or 14mg dose.
• Mounjaro (tirazepatide) – strictly speaking the is a dual incretin agent, i.e. it acts on both GLP-1 and GIP receptors. Clinical trials have shown it to be superior to all the above GLP-receptor agonists in controlling blood sugar and weight loss in patients with Type 2 diabetes.

GLP1-receptor agonist medications and weight loss

Only one GLP-1 RA is registered in South Africa for weight loss:

Saxenda (liraglutide) – you will note it is the SAME product as Victoza but when used for weight loss it is marketed in larger doses, up to 3mg daily, and under a different name.

Ozempic is not registered for weight loss in South Africa. The molecule, semaglutide, is registered overseas for weight loss under the name Wegovy.  As has been seen with liraglutide, semaglutide needs to be given in higher doses for weight loss – up to 2.4mg weekly. The STEP clinical trials demonstrated weight loss of approximately 10-15%. STEP 4 particularly looked at what happened after the medication was stopped: after using semaglutide 2.4mg weekly for 20 weeks, subjects had treatment discontinued and had regained 6kg by the end of the trial. This emphasizes the chronic nature of obesity management.

People are using Ozempic off label for weight loss, including celebrities who posted on social media of its effectiveness. This, unfortunately, resulted in a run on the drug and stocks plummeted. This has made it difficult for people with diabetes using Ozempic to access the medication.

Mounjero is not yet registered for weight loss but there is no doubt that it will be (possibly under a different trade name) as clinical trial results show subjects are shedding up to 20% of body weight. This is the most effective weight loss medication to date.

GLP-1 receptor agonists side-effects

The most common side-effects are gastro-intestinal: nausea, vomiting, diarrhoea, abdominal cramps, and heartburn. These side-effects can be avoided with the following measures:

1. Eat small portions.
2. Avoid fatty meals.
3. Chew food thoroughly.

These medications should not cause hypoglycaemia (low blood glucose) but if they are being added to insulin or other oral diabetes medications that can cause hypoglycaemia (sulphonylureas), low blood sugar levels must be watched for. The other medications can be decreased in dose.

A history of pancreatitis is a contra-indication to using these medications and they are not registered for use in pregnancy or when breast-feeding.

If a person has a history of thyroid cancer, they may be advised not to use GLP-1 receptor agonists. However, it is important to understand that this risk is theoretical based on rat studies. No case of thyroid cancer due to these medications has been described in humans.

Medical aid reimbursement

Many medical aids do reimburse for this group of medications for people living with diabetes if diabetes is not controlled with 2 previous medications. Certain criteria must met, for example glucose levels not well controlled on other medications and an increased weight. Your doctor will usually have to motivate to get cover under chronic benefits. Medical aids do not recognize obesity as a chronic condition and will not cover medication to treat it. The cost of Saxenda at a dose of 3mg daily is over R4000 per month. This is a significant financial commitment. It is vital to remember that Saxenda’s effects will be lost if the medication is stopped. Treating obesity should be approached in the same way as treating diabetes or hypertension – as a chronic condition.

The future

There is no doubt that the GLP-1 receptor agonists offer the best medical intervention for overweight and obesity to date. If they are used as part of a holistic approach to a healthy lifestyle then significant, sustained weight loss may be achieved. It remains to be seen if funders will reimburse for their use on chronic benefits and whether people will use them as a regular, chronic prescription drug.