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GLP-1 RAs – where are we now? What have we learned?
Pharmacist Deborah Evans runs a weight-management clinic at Remedi Health in Winchester. She has helped many people to lose weight and improve their health using the GLP-1 receptor agonist (RA) semaglutide (Wegovy) and combined GIP/GLP-1 RA, tirzepatide (Mounjaro). In this interview she describes our current understanding of GLP-1 RAs – ‘the fat jabs’ – and emerging findings from clinical practice.
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Interest in GLP-1 receptor agonists has grown significantly over the past 12-18 months, with frequent mentions in news and online discussions. These medications are a major advance in helping people lose weight, proving effective across different patient groups.
The key points from this interview are summarised below:
- Mechanism of action
GLP-1 receptor agonists (e.g. semaglutide) work in several ways:
- Slowing gastric emptying so that people feel full longer
- Boosting satiety so that smaller meals are satisfying
- Reducing appetite by directly influencing brain areas that control appetite.
- Balancing blood sugar – GLP-1 analogues prevent the release of glucagon, leading to more stable blood sugar levels and fewer glucose spikes after meals.
In addition, tirzepatide (Mounjaro) a dual agonist (with combined GLP-1 and GIP effects), enhances insulin secretion, especially during meals, and improves insulin sensitivity, working together with the GLP-1 effects
Clinical trials have indicated that tirzepatide results in a greater average weight loss – around 21-22%, compared to about 15% with semaglutide. Tirzepatide may be particularly suitable for obese individuals with pre-diabetes.
- Common side effects
The most common side effects are related to delayed gastric emptying, including reflux, nausea, vomiting and constipation. Patients should be counselled about what to expect and how to manage side effects.
Long-term side effects can include muscle loss (sarcopaenia) and osteoporosis.
- Obtaining a supply of GLP-1 RAs
An in-person, face-to-face consultation is the safest way to obtain a supply – so that BMI can be verified and the risks and benefits of GLP-1 treatment can be assessed.
These medicines are approved for adults with a BMI of 30 or a BMI of 27 with a comorbidity such as a hypertension or pre-diabetes. NHS thresholds can be higher. While the NHS route is an option, it may involve challenges, such as long waiting times and limited medication choices.
Patients should be wary of obtaining supplies of GLP-1 RAs from unregistered online providers because of the risks of counterfeit medicines and inappropriate prescribing. Patients should check that the online pharmacy is registered with the General Pharmaceutical Council (GPhC) and has a visible GPhC number on its website.
The General Pharmaceutical Council has issued Guidance for registered pharmacies providing pharmacy services at a distance, including on the internet to strengthen safeguards for people obtaining supplies online.
- Ongoing management
Prescribers should schedule regular follow-up appointments to evaluate treatment efficacy, monitor side effects, and adjust dosages as necessary. The following points should be covered:
Understanding the science: Discuss the importance of understanding the science behind weight loss to help patients psychologically adapt to weight loss, overcome body dysmorphia, and address fears of eating properly.
Lifestyle changes: Emphasize the importance of lifestyle modifications, including diet and exercise, for achieving sustainable weight management
Strength training: Throughout the use of these drugs, strength and muscle mass training are crucial for preventing sarcopenia.
Protein intake: Advise patients to consume protein-rich foods to help maintain muscle mass.
Referrals: If patients do not respond to maximum doses of either medication, consider referral to an endocrinologist.
Long-term strategies: Discuss strategies for maintaining weight loss after stopping medication, focusing on gradual dose reduction and continued lifestyle modifications.
- Dosing considerations
Doses are individual and not everyone needs the maximum dose. Some people respond to one drug but not the other and switching is possible
- Stopping treatment with GLP-1 RAs
There is very little data to help prescribers decide how to take people off the medication. The body is biologically designed to regain the weight that has been lost. Stopping treatment abruptly often leads to regain of weight. One strategy is “to come down the doses just as you went up them” to mitigate this effect.
- Communication with GPs
Private providers of GLP-1 RAs should inform the patient’s GP (with the patient’s consent) that they are taking these medications. There may be interactions with other medicines and it could be important if the patient becomes pregnant or is planning elective surgery. Patients taking GLP-1 or GIP/GLP1 RAs may be at risk of aspiration under general anaesthesia (see MHRA guidance).
Conclusion
GLP-1 and GIP/GLP-1 receptor agonists represent a significant advance in the treatment obesity and related metabolic disorders. Effective use of these agents will lead to better patient outcomes and transform the way in which weight management is approached.
About Deborah Evans
Deborah Evans, a pharmacist with 40 years of experience, who specialises in women’s hormonal health and weight management. She is the superintendent pharmacist and clinical director at Remedi Health. About 80% of her time is spent in the clinic facing clients.
