Our expanding toolbox: Designing personalised strategies in today’s new obesity medicine world

When I began practicing obesity medicine nearly 20 years ago, it was difficult for my patients to attain significant long-term weight loss without metabolic and bariatric surgery. However, the development of new pharmacotherapy options over the last 10 years has revolutionised obesity care.

Today, I direct a programme that provides ongoing, patient-centric support based on the Obesity Medicine Association’s four pillars of obesity treatment: nutrition, behaviour, physical activity, and medical management (which includes pharmacotherapy, procedures, and optimisation of other conditions related to or exacerbating obesity). An expanding toolbox of weight loss medications makes it possible to develop new tailored and personalised strategies for achieving and maintaining healthy weight.

Ongoing challenges in treating obesity

A primary challenge in treating obesity is that many patients are able initially to lose weight, but most struggle to maintain or continue losing weight. This is due to compensatory changes in hormones that regulate appetite, reduced energy expenditure, and increased appetite that occur when caloric intake is reduced.¹ Despite the long-term physiologic effects of caloric restriction, obesity has long been treated acutely, even though it is a chronic condition. The reality is that diet and exercise alone simply are not sufficient to maintain healthy weight over the long term for most people — as many of my patients and millions of people around the world have learned repeatedly.

Obesity is driven by complex factors, including physiologic, psychologic, and socioeconomic. Physiologic factors such as basal metabolism and co-morbidities (diabetes, metabolic disorders, hypothyroidism, polycystic ovary syndrome, and menopause) can cause weight gain. Mental health issues play a significant role in obesity. Conditions like depression and anxiety can lead individuals to turn to food for comfort or as a coping mechanism, rather than seeking healthier ways to manage their emotions. Low self-esteem and feelings of failure associated with obesity can further exacerbate psychological distress and perpetuate unhealthy eating habits. Socioeconomic factors also contribute to obesity by making it difficult for individuals to afford, access, or have time to prepare healthy food options. The combined and complex effects of obesity also lead to conditions including cardiovascular disease, cancer, and metabolic disease.

Tailored strategies are essential for improving obesity medicine outcomes

Every individual is more than their weight — or the number they hope to see on the scale. Consequently, it’s important to design treatment strategies around the patient as a person and not just their weight loss goals.

Co-morbidities need to be considered, as some may contribute to obesity, in which case treating the co-morbidity must be part of the obesity treatment strategy. Similarly, co-morbidities may influence the obesity treatment strategy if they present a contraindication or reason to use a particular weight loss medication. Health history is also important because many patients have already pursued weight loss strategies (including lifestyle changes and prescription weight loss medications). Understanding what has or hasn’t worked for an individual patient is essential for designing a tailored treatment with the greatest likelihood of success.

Many weight loss medications are not included in insurance coverage, creating economic barriers to care. As a result, cost-effectiveness may play a bigger role in the choice of weight loss medication than for other pharmaceutical classes. A recent analysis by the Institute for Clinical and Economic Review (ICER), found that phentermine/topiramate (QSYMIA) is cost-effective compared with life-style change, while GLP-1 agonists (including Wegovy and Saxenda) and bupropion/naltrexone (Contrave) are not cost-effective at their current prices.²

Patient preference should also be considered, as selecting a medication that the patient will take as prescribed is essential for adherence and optimised outcomes. Additionally, an oral once-daily option (such as phentermine/topiramate) may enable improved adherence for some patients compared with other oral weight loss medications that are dosed more frequently (both during titration and once full dosing has been reached).

Appropriate use of weight loss medications

The GLP-1 agonists are an important new class of weight loss medications. However, while they may be effective options in patients with diabetes or prediabetes they may not be appropriate for all patients. For example, GLP-1 agonists are contraindicated in patients with a history of pancreatitis, gastroparesis, or medullary thyroid cancer. As few insurance plans cover these medications for the treatment of obesity, many patients may not be able to afford the list price, which is about $16,000 per year. Some patients may be averse to an injectable therapy or may have other health issues that make an injectable therapy less appropriate than an oral medication.

While the GLP-1 agonists are garnering significant attention in the lay and medical communities, it is important to recognise that established weight loss medications continue to have an important role to play in designing tailored treatment options. Oral medications have well-established safety and efficacy profiles and, as noted above, can be more cost effective. An oral weight loss medication (phentermine/topiramate) is also approved for use in paediatric patients (ages 12-17 years). Several oral options (including phentermine/topiramate and bupropion/naltrexone) are approved for chronic use — an important feature, given the chronic nature of obesity.

As with all medications, the positive or negative impacts of oral weight loss medications on other health metrics or patient populations should also be considered. For example, bupropion/naltrexone can cause an increase in systolic and/or diastolic blood pressure, as well as an increase in resting heart rate and is contraindicated in patients with uncontrolled hypertension.³ Similarly, phentermine/topiramate may also increase heart rate,⁴ however, it has been shown to reduce blood pressure,⁵ which could be beneficial in patients with cardiovascular risk factors. Additionally, due to potential foetal toxicity, it should only be taken by women of child-bearing potential if they are using appropriate contraception.⁵

Navigating an evolving landscape for optimal patient outcomes

In a rapidly evolving landscape, weight loss medicine specialists need to educate our patients and colleagues about the risks, benefits, and limitations of weight loss medication options. It is important that patients and clinicians understand that the response to different medications can vary from one person to the next. The non-response rate to each of the currently available weight loss medications is 10-20%, including the GLP-1 agonists. Patients should be counselled accordingly, both to manage expectations and to reassure them that there are other options to consider if initial therapy isn’t effective.

Weight loss among responders can vary, so non-scale victories such as improved health, well-being, movement, and confidence should be appreciated, rather than focusing solely on trying to achieve the maximum loss observed in clinical trials of a particular medication. Patients and clinicians should also understand that the safety profile of phentermine/topiramate is distinct from that of fenfluramine/phentermine (fen-phen), a weight loss medication withdrawn from the market in the late 1990s following reports of heart valve defects in 24 patients.

Most patients will regain weight once they discontinue medication. HCPs should discuss this with their patients prior to initiating a medication regimen and should focus on designing a treatment regimen that integrates the four pillars of obesity treatment and can be followed chronically. Perhaps most importantly, patients, HCPs, and society as a whole need to recognise and acknowledge that weight and health are not the same thing. Weight loss medicine specialists and other healthcare providers need to consider patients’ health and weight holistically, with a goal toward reducing health risks, improving health outcomes, and helping patients feel comfortable in their own skin, regardless of the number on the scale.