Obesity: weight-management options a doctor considers

Obesity is a complex medical condition. The doctor evaluates metabolic, hormonal and cardiovascular factors before proposing any option.

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What it is

Obesity is assessed individually rather than through a fixed checklist — metabolic, hormonal and cardiovascular history all factor into what, if anything, a doctor proposes. The condition is defined by a body-mass index (BMI) of 30 kg/m² or higher, though waist circumference and the presence of weight-related complications add clinical precision to the risk assessment.

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How the weight-management medicines work

Semaglutide is a GLP-1 receptor agonist with 94% sequence homology to native human GLP-1. It activates GLP-1 receptors in the hypothalamic arcuate nucleus and the nucleus of the solitary tract in the brainstem — both regions that integrate satiety signals — reducing appetite and energy intake. It also activates GLP-1 receptors on pancreatic β-cells, enhancing glucose-stimulated insulin secretion in a glucose-dependent manner, and on gastric smooth muscle, slowing gastric emptying. Tirzepatide is a dual agonist at both the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor. GIP receptor activation in adipose tissue may improve lipid buffering and insulin sensitivity, and centrally it appears to enhance the satiety signal beyond GLP-1 agonism alone, which is consistent with the larger weight reductions seen in trials.

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What the pivotal trials showed

The STEP 1 trial (Wilding et al., NEJM 2021; PMID 33567185) was a double-blind, placebo-controlled, phase 3 RCT that randomised 1,961 adults with obesity (BMI ≥30) or overweight (BMI ≥27 with ≥1 weight-related complication, without diabetes) 2:1 to once-weekly subcutaneous semaglutide 2.4 mg or placebo, both with lifestyle intervention, across 129 sites in 16 countries for 68 weeks. The co-primary endpoints were percentage change in body weight and the proportion achieving ≥5% weight loss at week 68. Mean weight loss was 14.9% with semaglutide versus 2.4% with placebo; 86.4% of semaglutide recipients lost ≥5%. The most common adverse events were gastrointestinal (nausea 44%, diarrhoea 32%, vomiting 24%); 4.5% of semaglutide participants discontinued treatment because of gastrointestinal events. The trial excluded people with diabetes and measured weight change rather than hard cardiovascular endpoints. The SURMOUNT-1 trial (Jastreboff et al., NEJM 2022; PMID 35658024) was a double-blind, placebo-controlled, phase 3 RCT that assigned 2,539 adults with obesity (BMI ≥30) or overweight (BMI ≥27 with ≥1 weight-related complication, without diabetes) in a 1:1:1:1 ratio to once-weekly subcutaneous tirzepatide at 5 mg, 10 mg, or 15 mg, or placebo, all with lifestyle intervention, across 119 sites in 9 countries for 72 weeks. Mean weight loss was 15.0%, 19.5%, and 20.9% at the three doses respectively, versus 3.1% for placebo. Discontinuation due to adverse events occurred in 4.3%, 7.1%, 6.2% and 2.6% of the 5-mg, 10-mg, 15-mg and placebo groups respectively. The trial did not include people with diabetes and the measured cardiometabolic variables at baseline were relatively normal, which may have limited the measurable improvement in those markers.

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Population considerations

GLP-1 receptor agonists are contraindicated in people with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN 2), because rodent studies showed GLP-1 agonism can promote C-cell hyperplasia and C-cell tumours. Whether this risk exists in humans is unconfirmed, but the contraindication is maintained as a precaution. Semaglutide and tirzepatide have not been studied in pregnancy and should be discontinued at least two months before a planned pregnancy. In hepatic impairment, semaglutide exposure is not clinically significantly altered; there is limited experience with tirzepatide. In severe renal impairment (eGFR <30 mL/min/1.73 m²), semaglutide exposure increases; use is not recommended below this threshold.

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Treatments a doctor considers

A licensed doctor decides case by case, never automatically — payment for the medical consultation is only taken once an option has been reviewed.

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How Hi Doctor handles it

The questionnaire covers height and weight, medical history, current medication and previous weight-loss treatment; a body mass index is calculated from the answers and forms part of the eligibility decision — see how eligibility works and how safety checks run. Weight loss is available as a one-off consultation or an ongoing plan; the cost is set out on pricing. Any medicine a doctor prescribes is paid separately at a pharmacy.

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