Pharmacotherapy in Obesity Management
The first step is to review all medications that a patient is prescribed, with a view to identifying any that may be contributing to challenges with weight management. It may be possible to reduce the dose, wean down to discontinuation, and consider an alternative if appropriate.
If it is not possible to make a change, it is important to discuss this with the patient, so you can agree together that the benefits of the medication outweigh the risks of weight gain, and help the patient to understand why they may find weight management more challenging while taking that medication.
The Clinical Practice Guideline (CPG) for Management of Obesity in Adults in Ireland has a useful table in Chapter: Clinical Assessment of People living with Obesity – Page 17&18, Table 9
Ref: ASOI Adult Obesity Clinical Practice Guideline daptation (ASOI version 1, 2022) by: Duggan D and Kearney C, Hynes M, Manning S, O’Malley E. Chapter adapted from: Rueda-Clausen C, Poddar M, Lear S, Poirier P, Sharma A. Available from: https://asoi.info/guidelines/assessment/
There following medications are licensed and available for treatment of obesity in Ireland:
Orlistat (Xenical/Alli)
Naltrxone/Bupropion (Mysimba)
Liraglutide (Saxenda)
There is a lot of coverage of obesity medications in the media, so you may be asked about availability of other medications, such as Wegovy (Semaglutide 2.4mg) and Mounjaro (Tirzepatide). These medications are being launched in Ireland this year, Mounjaro in February 2025 and Wegovy in April 2025. They have been shown in studies to be very effective in the treatment of obesity and diabetes. Unfortunately for many patients who may benefit from these medications, cost may be a barrier to access, as there is currently no indication of reimbursement under GMS, LTI or DPS. Hopefully this situation will improve in future and we will update as the situation evolves.
Ozempic (Semaglutide 1.0mg) is licenced for treatment of type 2 diabetes. As with other GLP-1 therapies, it can be an effective treatment for people with obesity who do not have diabetes, and therefore is sometimes prescribed for this indication off-licence (off-label).
You can find detailed information about the available medications in the CPG for the Management of Obesity in Adults in Ireland, Chapter: Pharmacotherapy in Obesity Management – ASOI Adult Obesity Clinical Practice Guideline Adaptation (ASOI version 1, 2022) by: Le Roux C W1, Fitzgerald I2, Neff K3. Chapter adapted from: Pedersen SD, Manjoo P, Wharton S. Available from https://asoi.info/guidelines/pharmacotherapy/
GLP-1 agonist (single agonist) medications such as Liraglutide and Semaglutide, and dual agonists of GLP-1 and GIP such as Tirzepatide, are part of a group of effective obesity medications termed Nutrient Stimulated Hormone Therapies (NUSHs). There are also triple agonist medications in development, such as Retatrutide, an agonist of GLP-1, GIP and Glucagon receptors, and this medication has demonstrated promising results in Phase 2 trials.
Due to rapid evolution of these medications over the last few years, in addition to significant general public and media interest, there is a lot of misinformation circulating in relation to these medications. You can read more about this in Common questions/concerns about GLP-1 agonists and other NuSH therapies
Liraglutide (Saxenda, max dose 3.0mg) is currently the only licensed and available GLP-1 receptor agonist for obesity treatment in Ireland.
Liraglutide is also available as Victoza (max dose 1.8mg) when prescribed in diabetes management. This is less effective for weight management at the lower dose, but some patients treated with this dose for diabetes management have found it helpful for weight management.
Semaglutide (Wegovy max dose 2.4mg) (or Ozempic max dose 1.0mg when prescribed in diabetes management and off-licence use in obesity treatment).
Patient Selection
- BMI ≥ 30 or BMI ≥ 27 with an obesity-related health complication.
- Evaluate for contraindications such as a history of pancreatitis, active/symptomatic cholelithiasis or a family history of medullary thyroid carcinoma.
Patient Education
Taking the time to educate patients about these medications will benefit not only the patient but also HCPs. It will give patients confidence to manage common issues that arise, so they do not need to present as frequently with concerns. By taking the time to thoroughly explain the potential benefits, potential side effects, and correct usage of NuSH therapies, HCPs can improve patient adherence, reduce the chance of discontinuation, optimise treatment outcomes, and empower patients to take an active role in their health management. Furthermore, informed patients are better equipped to recognise and report significant adverse effects early, enabling timely adjustments to their treatment plan and enhancing overall safety and efficacy.
Management of short-term or mild GI side effects
Many patients will use these therapies without any side effects. However, all patients should be counselled regarding the risk of common side effects. This will help to reassure patients that some side effects do not necessarily indicate a problem with the treatment. Mostly side effects are mild to moderate in nature.
Nausea
Nausea may typically affect about a third of patients. Before initiating therapy, it is important to ensure patients are eating regular meals. The addition of nausea in a patient who already skips meals or has disordered eating may put them at risk of under-nutrition. Nausea can vary from the first day or two after administration to being more intense. It may impact patients at initiation or only when they reach high doses. For most patients, nausea will resolve within 4-6 weeks. Patients should be advised on potential management approaches that may be effective in mitigating nausea. These include:
- Reducing meal size
- Resist the feeling of having to ‘finish everything on the plate’
- Eating slowly
- Eating mindfully (not watching TV or other screens) so they may be more attuned to the satiety signal that prompts them to stop eating once full
- Avoiding eating when not hungry
- Focus on protein-rich foods
- Moderating intake of alcohol and fizzy drinks (particularly in the context of nausea and dyspepsia)
Infrequent episodes of vomiting may occur in a patient eating larger portions or pushing past the feeling of satiety, and the above advice would also apply.
If vomiting persists in spite of following the above advice, the dose should be reduced, and if this continues at the lowest dose the medication should be stopped.
It is worth pointing out to patients that GI side effects are not ‘how the medication works’, and they should not continue taking a medication that is continuing to make them unwell.
Frequent vomiting can sometimes be an indicator of binge eating behaviours or binge eating disorder. Ideally this should be screened for before initiating therapy and the patient referred if appropriate to psychology services.
Constipation
Ask about bowel habit prior to treatment. NuSH therapies can decrease gastric emptying and gastric peristalsis. If patients report constipation at baseline, consider addressing this (e.g. recommending increasing dietary fibre and water intake) prior to starting treatment. Many patients are not drinking enough water, encouraging adequate hydration is important for general health in addition to preventing and managing constipation.
Advise the patient on how to manage any potential worsening of constipation upon initiation and titration of the medication – e.g. OTC laxative preparations, red flags and when to attend the GP for assistance.
If significant constipation persists in spite of usual management measures, the dose should be reduced, and if this continues at the lowest dose the medication should be stopped.
Diarrhoea
Loose bowel motions or diarrhoea, like nausea, usually pass after about 4-6 weeks. Emphasise the importance of drinking plenty of water and staying well-hydrated if this occurs. The following may help to mitigate discomfort and enhance tolerance to the medication:
- Smaller more frequent meals
- Staying well hydrated
- Avoid high fat or highly processed foods
- Avoid high sugar drinks and minimise caffeine
- Include high fibre foods such as fruit, vegetables and wholegrain cereals
- In some cases, the use of OTC anti-diarrhoeal medications, such as loperamide, may be recommended, but patients should consult with healthcare provider before using these
- Dose reduction may be indicated
The medication should be discontinued if significant diarrhoea is persisting even on the lowest dose.
Management of more persistent or severe GI side effects
- Pause dose escalation and review
- Consider other conditions that may be causing similar symptoms
- Examine and work up for abdominal pain as appropriate (considering risk of pancreatitis and cholelithiasis) and evaluate the co-prescribing of other medications than can cause GI side effects e.g. metformin
- Adjustment to a lower dose should be considered in patients unable to tolerate GI side effects at the recommended maintenance/maximum dose – many patients have good efficacy at lower doses. You can reassure them it is fine to take a lower dose if they are experiencing positive effects at that dose (eg reduced hunger, increased fullness) without the side effects experienced at the higher dose. They can consider increasing to a higher dose at a later date, if appropriate.
Dosage review
Dosage may involve trial and error and should be tailored to the patient. The goal is a balance between tolerance and effect. This will be a joint decision made between clinician and patient. Start with the lowest dose to minimise GI side effects and titrate based on patient tolerance. Patients may need a slower dose escalation to allow side effects more time to settle. If a patient cannot tolerate maximum doses but gets results at a lower dose, they may stay at this point on the schedule – e.g. a patient can be maintained at 1.8mg Liraglutide if they cannot tolerate 2.4 or 3.0mg.
Supply is an issue and patients and clinicians alike can be unsure how to navigate this. Patients can have a situation where they have no supply for a month or more. If a patient reached maximum on the dosing schedule and had no issues with side effects and is without medication for about 4 weeks they can usually restart at the maximum dose. If a patient struggled with side effects to reach their current point of escalation, they should take a step back on the dosing schedule to build back up their tolerance.
Switching between NuSH therapies
Switching to an alternative NuSH therapy may be considered if the first agent trialled is not tolerated at the lowest dose, as there is variation in the GI tolerability of these medications. It is recommended to wait for GI symptoms to resolve before initiating the new medication. Further reading on switching between different agents is detailed in the paper referenced at the end of this page.
Weight loss expectations with NuSH therapies
The following is a rough guide to average weight loss associated with each medication:
- Liraglutide 1.8mg 5-10%
- Semaglutide 1.0mg 10-15%
- Semaglutide 2.4mg 15-20%
- Tirzepatide 20-25%
However, there is variation in response – some patients will not respond at all, while some will experience a significantly greater effect. It is important to explain this to patients, to help manage expectations, especially with all the media coverage, general misinformation, and expectations possibly informed by the experiences of their friends or relatives.
Patients living with obesity will often have been made to feel responsible for their condition, and could have significant feelings of shame and guilt if they do not have any, or less than average, weight loss. It is part of the role of the HCP to remind patients that all medications have variable efficacy and response from person to person, and if the medication is not effective for them, it is not their fault.
A review of response will form part of follow up, and usually weight loss of at least 5% at 6 months would be the target to continue therapy. However, if a patient was on a weight gain trajectory prior to starting the medication, achieving weight stability may be an acceptable outcome to clinically justify continuing the medication (although reimbursement approval criteria may not support this clinical indication).
It should be highlighted to patients that NuSH therapies are usually continued long-term in the treatment of the chronic disease of obesity. There may be some exceptions, but in general, in the context of complex obesity, if the medication is discontinued it is likely that weight regain will occur.
Treatment should be stopped in patients who are unable to tolerate NuSH therapies despite efforts to alleviate side effects. It may be possible to consider suitability for a different class of obesity pharmacotherapy.
Conclusion
NuSH therapies are a valuable addition to the therapeutic management of obesity. By carefully selecting patients, starting at low doses, escalating doses appropriately, educating patients, and monitoring regularly, HCPs can maximise benefits and minimise potential risks. As always, individualising patient care and staying updated with the latest guidelines and evidence will ensure optimal outcomes.
If you are interested in learning more about practical aspects of prescribing GLP-1 agonists, including trouble-shooting of possible side effects, please read the following paper…
Managing the gastrointestinal side effects of GLP-1 receptor agonists in obesity: recommendations for clinical practice. S Wharton, M Davies, D Dicker, I Lingvay, O Mosenzon, DM Rubino & SD Pedersen (2022) Postgraduate Medicine, 134:1, 14-19, DOI: 10.1080/00325481.2021.2002616
Link to article and 3 min summary video: https://doi.org/10.1080/00325481.2021.2002616
If you are interested in learning more about practical aspects of switching from one GLP-1 agonist to another, please read the following paper.…
Switching Between Glucagon-Like Peptide-1 Receptor Agonists: Rationale and Practical Guidance. JP Almandoz, I Lingvay, J Morales, C Campos (2020) Clin Diabetes, 38(4):390-402, DOI: 10.2337/cd19-0100
Link to article: https://pmc.ncbi.nlm.nih.gov/articles/PMC7566932/
If you would like to access the Clinical Practice Guideline for the Management of Obesity in Adults in Ireland Chapter on Pharmacotherapy, this and other CPG chapters are available at the following links….
Pharmacotherapy in Obesity Management – ASOI Adult Obesity Clinical Practice Guideline Adaptation (ASOI version 1, 2022) by: Le Roux C W1, Fitzgerald I2, Neff K3. Chapter adapted from: Pedersen SD, Manjoo P, Wharton S.
Available from https://asoi.info/guidelines/pharmacotherapy/
Why should I prescribe medications to treat obesity?
Obesity medications are an important part of the treatment of the chronic disease of obesity, in parallel with support for important lifestyle measures such as healthy eating and movement, healthy sleep pattern, social inclusion, stress management and mental health support when needed.
They should not be referred to as ‘weight loss medications’, as obesity treatment has a focus on health improvement, and weight loss is just one part of holistic management of this disease. This is the same approach used in all chronic diseases eg diabetes management is more than just lowering glucose levels.
Should I be concerned about prescribing obesity medications as the patient will most likely need to take the medications long-term?
Just as with other chronic diseases, medications that are effective at symptom management and improving quality of life, with good safety profiles, are prescribed long term. If blood pressure medication is discontinued blood pressure is likely to increase. The goal of chronic diseases management is to help people live well with the disease, and part of this approach includes long-term effective medications.
‘If we prescribe these medications, are we not encouraging people to ‘avoid responsibility’, rather than focusing on healthy lifestyle?’
Healthy lifestyle measures such as healthy eating and movement, healthy sleep pattern, social inclusion, stress management and mental health support when needed, are the cornerstone of managing all chronic diseases.
Just as with other chronic diseases, we understand that when the disease has higher severity and complexity, some people will need effective medications, in addition to healthy lifestyle measures. It is not one versus the other, this is about holistic long-term chronic disease management, and the principles of care are the same as for other chronic diseases.
Lifestyle measures alone are sufficient treatment for a very small percentage of people with obesity. This can be compared to the small percentage of people with type 2 diabetes who respond to lifestyle measures alone; the majority of people with type 2 diabetes need effective medications in addition to lifestyle treatment. If we did not have access to diabetes medications there would be substantial diabetes-related microvascular and macrovasular disease burden. This is the situation we currently have with a high burden of obesity-related complications, for people living with obesity who are unable to access effective obesity medications.
‘I am hesitant about prescribing Obesity medications as they do not treat the root causes of obesity’
How many drugs treat the root causes of disease? Do medications for asthma improve air quality? Do analgesic medications reduce injuries? Do statins reduce saturated fat in food?
Many non-communicable diseases (NCDs) result from our modern environment and lifestyle. Health promotion and prevention measures are important and necessary at population health level. They are important strategies to address primary, secondary and tertiary prevention of chronic NCDs.
As with the above discussion of lifestyle measures, it is not a case of one versus the other – prevention and treatment are both important. Medication may be needed for less people in future if public health measures are successful, but medication will always be needed for people who are living with disease.