Tirzepatide, under the brand name Mounjaro®, is the newest weight loss injection on the market and was approved by the UK government for weight management and weight loss in November 2023.1  This medication has been used in the NHS to treat type 2 diabetes since October 2023 and it should be available through the NHS for weight management purposes in early 2025.2, 3  Private GP’s can already prescribe this medication for both conditions. The UK government has authorised the use of this medication for weight management purposes in adults with a BMI of 30kg/m2 or more, unless someone also has other weight-related health problems like prediabetes, high blood pressure, high cholesterol or heart problems, in which case the BMI cut-off reduces to 27-30kg/m2. 1  The safety and effectiveness of tirzepatide has NOT YET been established in people under 18 years of age.4

How it works (5)

Tirzepatide is a once weekly injection that binds to and activates both the glucose-dependent insulinotropic polypeptide receptors (also called gastric inhibitory polypeptide or GIP) and the glucagon-like peptide-1 receptors (GLP-1) in the body. That means it:

• Helps the body release more insulin when blood glucose levels are high.
• Makes the body more sensitive to insulin.
• Stops the liver from making and releasing too much glucose.
• Slows down how quickly food leaves the stomach, which reduces hunger and increases satiety. This can help people eat less and lose weight.

Tirzepatide comes in doses ranging from 2.5 – 15mg.

Tirzepatide versus other weight loss injections

Older weight loss injections like semaglutide and liraglutide, only activate the GPL-1 receptors in the body whereas tirzepatide activates both GPL-1 AND GIP receptors. This dual action of tirzepatide is believed to be the reason it is more effective at reducing weight and blood glucose levels compared to other brands.6  Tirzepatide is therefore considered to be better value for money. 7

For people taking tirzepatide: (8)

• 81.8% lost 5% or more of their body weight,
• 62.1% lost 10% or more of their body weight, and
• 42.3% lost 15% or more of their body weight within 365 days.
• The average weight loss was 15.3% at 12 months.

For those on semaglutide: (8)

• 66.5% lost 5% or more of their body weight,
• 37.1% lost 10% or more of their body weight, and
• 18.1% lost 15% or more of their body weight within 365 days.
• The average weight loss was 8.3% at 12 months.

However, if these injections are stopped, people tend to gain back a significant amount of weight.  For those who were on semaglutide, people tended to regain 2/3 of the weight they lost within 68 weeks. 9  Similar results have been found for tirzepatide, where people regained ~50% of the lost weight within 12 months. 10 Long-term use of these medications is therefore being promoted.

Effect on muscle mass (11, 12)

While there aren’t any specific statistics on tirzepatide, research has shown that 25-40% of the weight lost from GLP-1 weight loss medication is fat-free mass/skeletal muscle.  The clinical significance of this is still unclear, but preliminary evidence suggests it may relate to reduced muscle fat infiltration (which may actually be beneficial).  However, much more research is needed.  Certain populations are already at higher risk of sarcopenia and impaired muscle function and will require additional consideration, monitoring and support.  For example, those who are older, who get little to no exercise, who have a poor nutritional status and/or who have a “severe disease,” will need to carefully consider the impact on muscle function before taking these medications.  Changing someone’s diet to a moderate protein intake is therefore critical in these groups to help preserve lean body mass. Endurance and resistance-type exercise can also help preserve muscle mass, but the fatigue caused by GLP-1 receptor agonists can make this difficult.

Is tirzepatide available on the NHS?

NICE is expecting to publish their guidance on the use of tirzepatide for weight management in December 2024.3   This medication will have a phased roll out initially, and the first recipients will need to have a BMI over 40kg/m2 and at least THREE of the specified weight-related health problems: hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease.13  NICE will decide after that, whether the NHS will make it available to anyone else.

Risks and side effects (1,4, 14, 15)

Tirzepatide has similar side effects to other weight loss injections.

• Affects the absorption of medication – due to the delayed gastric emptying caused by tirzepatide, it can reduce the absorption of medications which are taken orally. For that reason, women using oral contraceptives should either use an additional barrier method of contraception or switch to a non-oral form of contraceptive, for the first four weeks when starting tirzepatide, and for four weeks each time the dose is changed. Patients on medications that are dependent on a threshold concentration, or requiring a narrow therapeutic index, will also need to be monitored more closely.
• Gastrointestinal symptoms – these are the most common side effects from tirzepatide and include nausea (affecting 12-20% of people), diarrhoea (12-17%), decreased appetite (5-11%), vomiting (5-9%), constipation (6-7%), dyspepsia (5-8%) and abdominal pain (5-6%). These symptoms tend to decrease over time. Tirzepatide is not to be used by people who have gastroparesis.
• Acute pancreatitis
• Hypoglycaemia (with concurrent use of insulin secretagogues or insulin). It is not to be used in people with type 1 diabetes.
• Serious allergic reaction (e.g. itchiness, eczema, anaphylaxis).
• Acute kidney injury in people who have pre-existing kidney problems and who then experience dehydration from diarrhoea, nausea and/or vomiting.
• Changes to vision.
• Acute gallbladder disease (in 0.6% of patients).
• This medication causes thyroid C-cell tumours, including thyroid cancer, in rats. It’s unknown if this medication causes the same effect in humans.  Not to be used in people with medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2) or who have a family history of these conditions.

Do clients using weight loss injections still need to see a dietitian? (16)

Absolutely!  Obese clients are at high risk of malnutrition, and nutrient deficiencies are common in this population (even more so after a major trauma).  A reduced food intake due to taking anti-obesity medication, can therefore increase a person’s risk of malnutrition even more.

Medical nutrition therapy (from a dietitian), is therefore needed alongside anti-obesity medication to:

• screen for malnutrition and nutrient deficiencies,
• ensure adequate intakes of protein, fluid, fibre and micronutrients (in spite of a low-calorie intake),
• provide specific advice for minimising loss of muscle and bone,
• monitor and/or flag up any gastrointestinal issues, changes to mood, disordered eating behaviours or other complications to the GP, and
• liaise with the GP regarding dose adjustments to other medications as weight declines (e.g. antihypertensive, antidiabetic medication, diuretics or thyroid medication).

The recommended frequency of dietetic input, alongside anti-obesity medication, is monthly appointments during dose titration and then every 3 months until the goals are met.  Input can reduce further during the weight maintenance phase.

To refer a case management or litigation client for a comprehensive dietetic assessment and report, contact Specialist Nutrition Rehab at 0121 384 7087 or info@specialistnutritionrehab.co.uk.

For more information on the safety and effectiveness of semaglutide and liraglutide, as well as considerations for weight loss injections in general, please go to our previous article: Pharmaceutical weight loss injections…do they work?