Mounjaro by Eli Lilly is the most recent weight loss medication to receive authorisation from the MHRA (Medicines and Healthcare Products Regulatory Agency). It follows in the footsteps of Saxenda and Wegovy, which were the first injectable drugs approved for weight loss in the UK. 

All these medications belong to a group of drugs called incretin mimetics – they mimic the action of hormones called incretins. There are various types of incretin; Saxenda and Wegovy both mimic the effect of a hormone called GLP-1, whereas Mounjaro is a dual-receptor drug, mimicking two incretins, GLP-1 and GIP. 

In this article, we will take a deep dive into the mechanisms behind Mounjaro and GLP-1 agonists to get to grips with how they work for weight loss. 

GLP-1 Medications

As mentioned above, both Saxenda (liraglutide) and Wegovy (semaglutide) belong to a group of drugs called GLP-1 receptor agonists. This means that they bind to GLP-1 receptors in the body. These receptors are the binding site for the glucagon-like peptide-1 (GLP-1) hormone. 

This hormone is secreted by cells in the gut and it has lots of different functions which are implicated in both weight loss and type 2 diabetes. Both Saxenda and Wegovy were originally developed to help people with type 2 diabetes. It was only after their release as diabetes medications, that their weight loss benefits were understood. 

Treating Type 2 Diabetes

When you eat foods high in sugar or carbohydrates, your blood sugar (glucose) levels increase. Sugar is a good source of energy, but high blood glucose can damage nerves and blood vessels. To counteract this, your body has a built-in mechanism to keep your blood sugar within certain limits. When you eat something high in sugar, beta cells in your pancreas secrete insulin. 

Insulin causes the sugar to move from your bloodstream into cells, where it can be used for energy. In type 2 diabetes, your cells have become resistant to insulin, so your cells cannot take in the sugar as easily. This means you need more insulin to get the sugar out of your bloodstream.

One of the effects of GLP-1 is to increase the secretion of insulin when your blood sugar levels are high. GLP-1 is naturally released by the gut when you eat, but in diabetes, this is not sufficient to control your blood sugar levels. For this reason, a drug that mimics the GLP-1 hormone can bind to the GLP-1 receptors and increase your insulin levels, giving you better glycaemic control (control of your blood sugar levels). 

GLP-1 also increases the number of beta cells in your pancreas and helps them to last longer. This means your pancreas has a greater capacity to produce insulin, which should make it easier to control your blood sugar. 

GLP-1 and Weight Loss

GLP-1 receptor agonists are approved for weight loss as well as treating type 2 diabetes. As well as helping to regulate blood sugar, the GLP-1 hormone also helps to slow down the digestive system, so it takes longer for you to absorb the nutrients from your meal. This is advantageous in diabetes, because it means that you absorb sugar from your food more slowly when your blood sugar is high, however, it is also very beneficial in weight loss. 

By slowing down the movements of your digestive system, GLP-1 also slows down the rate at which your stomach empties. This means that you may feel full more quickly when you eat, and you should also feel fuller for longer. This reduces your appetite, and combined with diet and exercise, can make it easier to lose weight..   

Mounjaro

How Mounjaro Works

Mounjaro (tirzepatide) is an incretin mimetic similar to Saxenda and Wegovy, but rather than working on just one receptor (GLP-1), it also acts on the GIP (gastric inhibitory polypeptide) pathway. GIP is also known as glucose-dependent insulinotropic polypeptide.

GIP and GLP-1 are very similar hormones and they have very similar effects. They are both naturally secreted by the gut when you eat food and they both help to increase your insulin levels in response to your blood sugar. Both GIP and GLP-1 also help to slow down your digestive system to help you feel fuller for longer. 

Surprisingly, GIP has actually been found to increase weight gain in individuals on a high-fat diet. This is because it increases fat deposition in body tissues. However, when combined with GLP-1 this effect is reversed and the weight loss effects of GLP-1 are enhanced. The exact mechanism behind this is not yet understood, but it is thought that long-term over-stimulation of the GIP receptor desensitises these receptors which actually reduces fat deposition leading to weight loss. 

GIP appears to maximise the effects of GLP-1. In much the same way that a bath is filled most quickly when both taps are turned on, the dual-action of Mounjaro produces much greater effects than if only one receptor type was stimulated. 

This was also demonstrated in clinical trials, which show that 42.3% of people taking Mounjaro for 12 months experienced a reduction in their body weight of at least 15% compared to only 19.3% of people on Wegovy. This positions Mounjaro as a significant improvement on Wegovy and other single-pathway weight loss drugs.

Mounjaro Side Effects

As with any medication, Mounjaro has a number of side effects. When used for weight loss, one of the most common side effects is that it can reduce your blood sugar levels. It is not surprising that there is a risk of hypoglycemia (low blood sugar) on Mounjaro, considering that this is one of the reasons Mounjaro is so effective in diabetes. 

Several other Mounjaro side effects result from the fact that Mounjaro acts on the digestive system. These include burping, constipation, diarrhoea, abdominal discomfort, nausea and vomiting. There are also various other common side effects including weakness, fatigue and allergic reactions. 

In rare cases, Mounjaro can lead to gallstones and an inflammation of the pancreas known as pancreatitis. For this reason, Mounjaro is not recommended for people with a history of pancreatitis or severe gastrointestinal disease. 

Animal trials do suggest that there is a potential risk of thyroid tumours called medullary thyroid carcinoma (MTC)  associated with Mounjaro, however, this has not yet been confirmed in humans. Nevertheless, because of the potential risk of these tumours developing, you should not take Mounjaro if you or anyone in your family have ever had MTC or if you have a hormonal condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Tri-Receptor Weight Loss Drugs

As discussed, Mounjaro is a dual-receptor medication, meaning that it works on two different pathways to help you lose weight. However, there are several drugs currently in development known as tri-receptor medications, which will work on three different pathways. These are expected to be even more effective than Mounjaro. 

Retatrutide, also by Eli Lilly, is one of the most promising of these new medications delivering a mean weight loss of 17.5% over just 24 weeks. Retatrutide is still in the early stages, so comparative studies with other treatments like Mounjaro and Wegovy have not yet been completed, but these initial results are very promising. 

Like Mounjaro, retatrutide works on GLP-1 and GIP receptors, but it also has an additional action on glucagon receptors. Glucagon is another hormone involved in regulating blood sugar; however, where insulin works by reducing blood sugar levels, glucagon helps to bring them back up again. More importantly, glucagon reduces hunger and helps you to feel full, reducing appetite and helping people lose weight. 

How to Get Mounjaro

As of February 2024, Mounjaro has become privately available for weight loss treatment. You can begin an assessment to receive Mounjaro through Simple Online Pharmacy. Once requested, your case will be reviewed by a doctor, who will assess whether the treatment is suitable for you. If appropriate, your medication will be dispensed and delivered to your home. 

Mounjaro is not currently approved for use in weight loss on the NHS. This is likely due to issues around the cost of the treatment and the availability of alternatives such as Wegovy. It is possible that Mounjaro weight loss prescriptions may be approved on the NHS in future, but there is no guarantee and it may be a long time before any approval is granted. 

Conclusion 

Mounjaro is a dual-receptor drug. Like its forerunners, Wegovy and Saxenda, Mounjaro acts on the GLP-1 receptors to control blood sugar and reduce appetite. However, Mounjaro also acts on GIP receptors as well. These work in much the same way as GLP-1 receptors, but they significantly increase the targets upon which the drug can act, allowing Mounjaro to deliver enhanced weight loss effects. 

Tri-receptor drugs that act on three different pathways are currently in development, but may deliver even greater weight loss results if they ever reach the market.  

If you would like to receive Mounjaro, you can fill out an assessment form to begin the process of receiving this weight loss medication.