Unfortunately, obesity is persistent and commonplace in today's society, resulting in global morbidity and mortality. Numerous medications have been studied to treat it, four of which shall be discussed in this article, followed by a section on the importance of behavioural intervention.
Tirzepatide
The New England Journal of Medicine recently published the results of a study examining the efficacy of tirzepatide—a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist (Jastrehoff et al, 2022). The trial was phase 3, double-blinded, randomised and controlled, with 2539 assigned adults with a body mass index (BMI) of 27 or more, and at least one weight-related complication, excluding diabetes. The participants were assigned in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or a placebo for 72 weeks, including a 20-week dose-escalation period. The researchers compared the percentage change in weight from baseline and examined to see if there was a weight reduction of 5% or more.
At baseline, the researchers recorded the mean weight to be 104.8 kg, with a mean BMI of 38.0 (and 94.5% of participants having a BMI of 30 or more). At week 72, the mean change in weight was a reduction of 15% with 5 mg, 19.5% with 10 mg weekly doses and a reduction of 20.9% weight with 15 mg weekly doses of tirzepatide. There was a reduction of just 3.1% in weight for the placebo group in the 72-week period. The percentage of participants who lost 5% or more of their body mass increased from 85% to 91% as the dose increased from 5 to 15 mg. For participants in the placebo group, only 35% of participants lost 5% or more of their body mass. In fact, 50% of those taking 10 mg tirzepatide and 57% taking 15 mg, saw weight loss of 20% or more of their body mass, compared with 3% in the placebo group.
Gastrointestinal issues of mild and moderate intensity were reported as common adverse events, and led to a small percentage of people in each dose category discontinuing medication, and it was noted these were more evident during dose escalation. Overall, the trial was a success and paved the way for a new and safe medication for people with obesity.
Semaglutide
A trial was conducted to test the efficacy of a weight loss drug for obese patients. Semaglutide was already known to be beneficial for weight loss but the team wanted to ascertain whether at a dose of 2.4 mg as an adjunct to lifestyle intervention, the drug would be efficacious (Wilding et al, 2021). The trial enrolled 1961 participants with a BMI of 30 or more who did not have diabetes. They were enrolled at a 2:1 ratio to groups either receiving 2.4 mg subcutaneous semaglutide once weekly plus lifestyle intervention, or placebo plus lifestyle intervention.
By week 68, the team noted a 14.9% mean reduction in body weight since baseline in the group receiving semaglutide, compared to reduced in the group receiving semaglutide, compared to just a reduction of 2.4% in the placebo group. Those in the semaglutide group also achieved higher rates of 5% or more body mass loss (86.4% compared with the placebo group at 31.5%). Compared to 12% in the placebo group, 69.1% of the semaglutide group achieved a 10% body mass reduction. Over half (50.5%) of the group receiving Semaglutide achieved 15% or more body mass reduction and 4.9% of those in the placebo group achieved this, with all results clearly showing the benefit of the Semaglutide adjunct.
The semaglutide group lost over 15 kg in total on average, compared with those in the placebo group losing just over 2 kg on average. Those receiving the drug also saw improvements in cardiometabolic risk factors, and showed a greater increase in participant-reported physical function since baseline, when compared with the placebo group.
Similarly to most medications for obesity, gastrointestinal symptoms were common adverse events, mainly being nausea or diarrhoea, although these were transient and mild to moderate, showing improvement with time. This led to 4.5% of those receiving the semaglutide to discontinue treatment, markedly more than the placebo group where 0.8% of participants discontinued treatment. It was clear on conclusion that semaglutide as an adjunct to other lifestyle measures was a benefit to patients with overweight or obesity (Wilding et al, 2021).
Orlistat
One of the main medications for obesity to first emerge was orlistat. The NHS (2022) reports that the medications confirmed to be safe for use for obesity are orlistat and liraglutide. Orlistat causes approximately a third of the fat consumed from food not to be absorbed, and to pass through the gut, meaning the calorific content is not absorbed by the body. This leads to weight gain prevention, but the NHS (2022) pointed out that this may not actually cause weight loss. Patients are expected to be participating in a balanced diet prior to commencing the treatment, having shown they are making an effort to lose weight through healthy lifestyle changes. The drug is only prescribed to those with a BMI of 28 or more and where there are weight impacted conditions such as hypertension or type two diabetes, or for someone with a BMI alone of 30 or more (NHS, 2022).
It is a short-term treatment that would be given for no longer than 3 months, unless the patient shows they have lost 5% of their body weight. The side effects are off-putting, with patients experiencing oily faeces, oily rectal discharge, and urgency to defecate. The NHS (2022) points out that these adverse effects are substantially reduced if someone sticks to a low-fat diet.
Liraglutide
Liraglutide works slightly differently, by causing the person to feel fuller and less hungry, and is taken as a subcutaneous injection once daily. This would normally be prescribed if other efforts such as diet and exercise changes have not worked, if orlistat has not worked, or where the person does not wish to have weight loss surgery. The patient would have a diet plan and exercise regime set out for them while taking the medication as an adjunct to these lifestyle changes.
Liraglutide is limited in its supply, as it is approved only to be prescribed to people with a BMI of 35 or more, or where the BMI is 32.5 or more and who belong to an at-risk ethnic group: south Asian, Chinese, black African or African-Caribbean origin. The drug would also be prescribed to those with a non-diabetic high blood sugar or where they are at risk of myocardial infarction or stroke, such as in people with hypertension (NHS, 2022). Similarly to orlistat, if the patient loses 5% or more of their body weight, they can continue at 3 months, otherwise the drug would be discontinued.
Behavioural interventions
Behavioural interventions are key whether prescribing weight loss medication or not. Madigan et al (2022) studied the effectiveness of such interventions in the primary care setting, carrying out a systematic review and meta-analysis of randomised controlled trials. The team specifically looked at trials of weight loss interventions for adults with a BMI of 25 or over, that compared the effect of the interventions with participants who received no treatment or had minimal interventions, examining weight change at 12 months follow-up compared to baseline.
Madigan et al (2022) found that behavioural weight loss interventions are effective when delivered in primary care to adults. Such interventions include changes to diet and exercise, using a tailored programme to encourage new behaviours. Some GP practices offer a tailored intervention programme to suit the individual need of that person, and these can be successful as a result of working on and improving existing levels of strength and physical capability, alongside other comorbidities that require management along the way.
More specifically related to diet, Ge et al (2022) examined the relative effectiveness of dietary macronutrient patterns and the effect of popular named diets on weight loss, while also looking for cardiovascular risk factor improvement in people who were overweight or obese. The authors found that there was moderate certainty to prove modest weight loss results from following most of the macronutrient diet options. More significantly, the evidence also showed there to be substantial improvements in cardiovascular risk factors, especially blood pressure. However, the team found that by 12 months, the effect on both weight loss and risk factors for the most part, disappeared. This raises the significance of popular debate over fad diets—they are short-term answers but overall do not lead to long-term outcomes that are positive for an overweight person's health. There are multiple popular diet programmes available, but whether they are healthy or effective is largely not well-studied.
Conclusion
Overall, it is for the practitioner to notice when a patient requires referral dependent on their BMI and comorbidities, to a weight loss reduction programme, or to their doctor for the potential option of medication to aid weight loss. It is also important to advise the patient on popular diet programmes, so as to avoid recommending these or validating their use if a patient discusses them. A balanced diet is important and specialist dietary advice through a weight loss programme is beneficial. Exercise interventions may also require a slightly more cautious approach if the patient is obese with a sedentary lifestyle and cardiovascular comorbidities that may increase the patient's risk of myocardial infarction and other conditions. Therefore, behavioural interventions should be tailored to suit the patient and advised by their weight loss programme.