Tirzepatide for obesity: precision prescribing beyond the number on the scales

About two-thirds of the UK population is living with overweight or obesity¹, yet the condition is still often perceived as a matter of willpower rather than a chronic, relapsing disease. In this interview, Sehar Shahid, independent prescribing pharmacist, founder of 24-hour Pharmacy and National Pharmacy Association board director for Scotland, explains the biology behind weight regulation, reviews the key trial evidence for tirzepatide (Mounjaro), and describes how she individualises treatment in her own weight-management clinic.

Obesity: a chronic, multifactorial disease

Despite classification by the World Health Organization as a chronic disease², obesity is still not consistently recognised as such in UK clinical practice, notes Ms Shahid. “It’s not as simple as eat less and move more,” she says. Genetics, epigenetics, social and cultural factors, environment, psychology and behaviour all contribute, meaning some people are more susceptible to weight gain than others.

Why weight loss is hard

Appetite and satiety are governed by three interacting brain systems: the mesolimbic system, which drives the hedonic “wanting and liking” of food; the hypothalamus, which regulates hunger, satiety and energy expenditure; and the prefrontal cortex, responsible for executive control and self-discipline. In a healthy weight, these pathways are balanced. In obesity, they become dysregulated: hunger hormone levels run higher than physiological need while satiety signalling is blunted, so patients eat more and register fullness later – a cycle that is not, Ms Shahid stresses, a failure of willpower.

GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) are naturally occurring gut hormones released after eating. They act on receptors in the brain, pancreas and adipose tissue. Weight-loss medicines mimic the actions of one or both of these hormones, reducing hunger and cravings, increasing satisfaction with smaller portions, improving insulin sensitivity and secretion, reducing glucagon secretion, and delaying gastric emptying so patients feel fuller for longer.

The clinical case for weight loss

Modest weight loss produces measurable benefit. A reduction of up to 5% of body weight begins to improve blood glucose, blood pressure, lung and kidney function, and outcomes in polycystic ovary syndrome and infertility. Beyond 5%, the risk of obesity-related cancers falls and joint pain and mobility improve; beyond 10–15%, cardiovascular mortality risk is significantly reduced. Patients with a BMI of 40 or above already have a life expectancy reduced by 8 to 10 years, so bringing BMI down also reduces the risk of diabetes, heart attack, stroke and cancer, says Ms Shahid.

Tirzepatide: indications and trial evidence

Tirzepatide is licensed for weight management, alongside diet and exercise, in adults with a BMI of 30 or above, or 27 or above with a weight-related comorbidity such as sleep apnoea, prediabetes, diabetes, hypertension or dyslipidaemia; it is also indicated for type 2 diabetes.

The SURMOUNT-1 trial randomised over 2,500 participants (average age 45, 67% female, mean 15 years living with obesity, baseline BMI around 38) to tirzepatide 5mg, 10mg or 15mg, or placebo. At week 72, placebo produced 2.4% weight loss, compared with 16% on 5mg, 21.4% on 10mg and 22.5% on 15mg – a difference of only one percentage point between the two highest doses. Waist circumference fell by almost 20cm on the 15mg dose, versus 3.4cm on placebo – “about eight belt holes,” says Ms Shahid. By week 20, patients on the 10mg and 15mg doses had already lost around 12.8% of body weight. DEXA scanning showed three times more total fat mass loss than lean mass loss, challenging the perception that tirzepatide causes disproportionate muscle loss – though some muscle loss accompanies any form of weight loss, and Ms Shahid counsels all patients on high-protein diets and strength training to help preserve muscle.

SURMOUNT-5, a head-to-head trial of tirzepatide 10mg/15mg against semaglutide 1.7mg/2.4mg in a similar population, found weight reduction of 21.6% with tirzepatide versus 15.4% with semaglutide at 72 weeks, and waist circumference reduction of 20cm versus 14.6cm. Notably, the results with higher dose semaglutide were comparable to those with tirzepatide 5mg – the second step of the titration schedule. Because most patients pay privately for treatment, Ms Shahid advises people to consider efficacy and time-to-target as well as cost. A longer titration period to reach equivalent results may not prove cheaper overall.

Individualising the dose

“It’s about slow and steady, not escalating every four weeks,” says Ms Shahid, who has no patients currently on the 15mg dose. Patients titrated too quickly to the maximum dose can find themselves with no further room to escalate once progress stalls. She increases the dose only when weight loss slows and appetite suppression wanes, provided side effects remain well controlled.

Safety and practical advice

Gastrointestinal effects – nausea, vomiting, constipation, diarrhoea, abdominal cramps – are common, particularly after starting or increasing the dose, but typically ease over time. Advice includes smaller, more frequent meals, mindful eating, 2–3 litres of daily fluid, and avoiding fatty, spicy or rich food, alcohol and fizzy drinks; a food diary can help identify triggers. Ms Shahid does not escalate the dose until side effects have settled.

Patients on insulin or sulfonylureas require dose adjustment to avoid hypoglycaemia, and prescribers should liaise with the clinician managing the patient’s diabetes. A history of pancreatitis warrants caution and patient education on warning signs such as severe abdominal pain radiating to the back; treatment should be discontinued if pancreatitis is suspected. Women of childbearing age should be advised to use barrier contraception for the first four weeks of treatment and at each dose escalation, since delayed gastric emptying may reduce oral contraceptive reliability.

Looking ahead

Ms Shahid is cautiously optimistic about retatrutide, a triple agonist currently in clinical trials, which may particularly benefit patients with a very high BMI or an inadequate response to existing agents. She warns strongly against unlicensed “black market” retatrutide already circulating: “please only ever use licensed medication.” She also welcomes the arrival of oral GLP-1 agonists, including newly launched oral formulations, which are bringing forward patients who had previously avoided treatment because of needle-phobia.

Ms Shahid also urges more careful language around obesity treatment, noting that terms like “skinny jabs” trivialise a prescription-only medicine for a chronic disease in a way clinicians would never apply to insulin or antihypertensives.

For Ms Shahid, the rewards of running a weight-management clinic lie well beyond the number on the scales. “You start peeling back all the layers,” she says, describing the improvements in confidence, relationships and comorbidities that follow sustained, individualised support.

References

1. NHS England. Health Survey for England, 2024. Jan 2026. https://digital.nhs.uk/data-and-information/publications/statistical/health-survey-for-england/2024
2. WHO Obesity and overweight. Dec 2025. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight

About Sehar Shahid

Sehar Shahid is the founder and superintendent pharmacist of 24HR Pharmacy, a UK online pharmacy. She is an independent prescriber.

Sehar serves as a Board Director for Scotland at the National Pharmacy Association (NPA), contributes to clinical training in obesity management, and mentors professionals through leadership and empowerment initiatives. She was recognised as Independent Prescriber of the Year at the Pharmacy Business Awards 2025.