Dr Angela Murphy explains why people are using Ozempic off-label for weight loss resulting in a shortage for people with diabetes who need it for glucose control, not only in SA but around the world.
The twin pandemics of obesity and Type 2 diabetes have created a need to find a common management pathway. 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 and lose meaningful weight.
Diabetes – diagnosed when fasting blood glucose is ≥7.0mmol/L, and/or two-hour post glucose drink test is ≥ 11.1mmol/L and/or HbA1c >6.5%
Obesity – body mass index (BMI) which is calculated by dividing height squared into weight: > 30kg/m2 = obese and 25-30kg/m2 is overweight
It’s important to measure waist circumference in patients to ascertain the degree of visceral fat. It’s this fat which causes most of the metabolic complications, especially diabetes.
A novel hormone pathway
The incretin hormones are produced in the cells lining the small intestine in response to digested food entering there. These hormones alert the pancreas to make insulin to control blood glucose at mealtimes. This system has been found to be sluggish in Type 2 diabetes, so medications were developed to improved incretin hormone levels.
There are two main incretin hormones in the human body: glucagon-like peptide 1 (GLP-1) and gluco-inhibitory peptide (GIP). The medications produced to increase GLP-1 levels are called GLP-1 receptor agonists and have made a significant impact on the treatment of both diabetes and obesity. They do this by:
- Stimulating the pancreas to increase insulin.
- Blocking the liver from producing glucose.
- Directly inhibiting the appetite centre in the brain.
- 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.
GLP-1 receptor agonists registered in South Africa for diabetes
- Byetta (exenatide) – This was the first GLP-1 receptor agonist in South Africa. It’s given as a twice daily injection within 60 minutes of breakfast and dinner. It’s effective in lowering blood glucose after meals but doesn’t have much effect on weight.
- Victoza (liraglutide) – This is given as a daily injection starting at a dose of 0.6mg daily and increasing to 1.8mg daily and has shown significant improvement in weight loss.
- Trulicity (dulaglutide) – This is a weekly injection given with a single-use device so the needle isn’t visible. It comes in one dose of 1.5mg weekly and has excellent glucose lowering properties but doesn’t result in significant weight loss.
- Ozempic (semaglutide) – This is a weekly injection where the dose is titrated from 0.25mg to 1mg depending on the blood glucose levels. Ozempic also lowers blood glucose levels effectively and has shown good weight loss.
GLP-1 receptor agonists not available in South Africa
- Rybelsus (oral 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 this is a dual incretin agent (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 glucose and weight loss in patients with Type 2 diabetes.
GLP1-receptor agonist medications and weight loss
Registered in SA
Only one GLP-1 RA is registered in South Africa for weight loss:
Saxenda (liraglutide) – You will note it’s the same product as Victoza but when used for weight loss it’s marketed in larger doses and under a different name.
Clinical trials showed that meaningful weight loss was achieved at a dose of 3mg daily, significantly higher than the doses used to treat diabetes. The best results were achieved in subjects who had already lost at least 5% weight on calorie restriction before starting Saxenda. Then over the course of 56 weeks they lost a further 6kg of body weight.
Not registered in SA
Ozempic (semaglutide) 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, Ozempic 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 emphasises 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. The tragedy of this is that people with diabetes using Ozempic for glucose control have struggled to get their supply; a problem both in South Africa and around the world.
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 reduced with the following measures:
- Eat small portions.
- Avoid fatty meals.
- 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 glucose 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 breastfeeding.
If a person has a history of thyroid cancer, they may be advised not to use GLP-1 receptor agonists. However, it’s 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. Certain criteria must be 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. Note: medical aids don’t recognise 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 R4 000 per month. This is a significant financial commitment. It’s 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.
Managing the combination of obesity, diabetes and pre-diabetes can be frustrating. A balanced lifestyle is the cornerstone to this, but it’s difficult for people to constantly be told to eat less and move more and still see no meaningful changes.
There is a great need for a pharmacological intervention and the GLP-1 receptor agonists are a step in the right direction. However, their use is restricted by possible side effects, cost, and the need for them to be used as ongoing treatment.
It’s my opinion that the reason we fail to achieve meaningful and sustained weight loss is that there is a tendency to look for a cure for overweight or obesity. It’s a concern that many people will use GLP-1 receptor agonist medications for short periods and once they achieve some weight loss, or if lucky even their goal weight, they will stop. After some months weight regain will start and the perception will be that these drugs are no better than any weight loss agent that has come before.
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.
MEET THE EXPERT
Dr Angela Murphy is a specialist physician and currently sees patients at Sunward Park Medical Centre. She retains a special interest in endocrinology and a large part of her practice is diabetes and obesity. She is a member of the Society of Endocrinology and Metabolism of South Africa and the National Osteoporosis Foundation and is actively involved in diabetes patient education. Living with diabetes in the family for 17 years has shown her that knowledge is power.
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