The connection between the pancreas, the gut and incretins – hormones released into the blood by the intestine in response to food – was established in the early twentieth century (Knudsen and Lau, 2019). With the incretin hormone glucagon-like peptide-1 (GLP-1) shown to account for up to 70% of insulin secretion in response to nutrient intake, its therapeutic potential in type 2 diabetes (T2D) was realised, leading to the development of semaglutide, which mimics GLP-1 by promoting insulin release and reducing the blood concentration of glucose (Knudsen and Lau, 2019).
Although semaglutide has been used in the treatment of T2D, Wilding et al (2021) reported the results of a double-blind trial of 1961 non-diabetic adults with a body-mass index (BMI) of 30 or greater, randomly assigned ‘to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention’. They found that obese or overweight non-diabetic adults ‘had a mean weight loss of 14.9% from baseline with semaglutide as an adjunct to lifestyle intervention. This loss exceeded that with placebo plus lifestyle intervention by 12.4 percentage points’ (Wilding et al, 2021).
In March this year, the National Institute for Health and Clinical Excellence (NICE) recommended semaglutide (sold as Wegovy) ‘alongside a reduced-calorie diet and increased physical activity to adults who have at least 1 weight-related comorbidity and a BMI of at least 35kg/m2’ (NICE, 2023a). However, significantly, ‘semaglutide is limited to 2 years because of restricted time in specialist weight management services and lack of evidence for longer use’ (NICE, 2023b).
NICE's endorsement comes two years after the United States Food & Drug Administration (FDA) declared that ‘this under-the-skin injection [sold as Ozempic] is the first approved drug for chronic weight management in adults with general obesity or overweight since 2014’ (FDA, 2021).
However, gastrointestinal disorders ‘occurred in more participants receiving semaglutide than those receiving placebo (74.2% vs 47.9%) … [and serious] adverse events were reported in 9.8% and 6.4% of semaglutide and placebo participants, respectively’ (Wilding et al, 2021). While the Electronic Medicines Compendium (EMC, 2023) lists adverse side effects for Wegovy (like retinopathy and pancreatitis), it does not include a warning that appears on the FDA's 2017 approval document for Ozempic, and further validated in 2020 (FDA, 2017). Under ‘warning: risk of thyroid c-cell tumors’ it states: ‘In rodents, semaglutide causes thyroid C-cell tumours. It is unknown whether OZEMPIC causes thyroid C-cell tumors, including medullary thyroid carcinoma, in humans as the human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined’ (FDA, 2017).
What has also not been determined is the extent to which human behaviour leads some individuals to favour an injected drug over a lifestyle change which could successfully address T2D without pharmacological side-effects. But is the patient to blame? Bikman (2020) is clear that before they meet patients, healthcare professionals will have undergone ‘countless hours of pharmacology and drug mechanism study, but maybe a handful of hours devoted to lifestyle.’
It is also clear that neither the food nor pharmaceutical industries will express unbridled enthusiasm for a drug-free intervention that promotes the consumption of proper food over junk eating. For example, as part of the title of a paper by Hall et al (2019) indicates, ‘Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain’, in which case should an ethical imperative not impel health professionals to steer their overweight patients away from ultra-processed diets as a starting point, rather than prescribing medication?
Meanwhile, mounting evidence shows that if patients are given appropriate support, they can influence their own conditions' outcomes. For instance, encouraging data from Unwin et al (2022) demonstrate for the first time the short-term clinical effectiveness of a ‘low-carbohydrate “real food” intervention delivered in an online group format with education and social support for individuals with food addiction symptoms.’ Further bolstering the evidence base favouring the efficacy of lifestyle intervention, pioneering work from Southport's Norwood Surgery GP practice in the UK shows (Unwin et al, 2023): ‘77% of those adopting a low-carbohydrate approach in the first year of their T2D achieved remission. This represents an important “window of opportunity” for further investigation.’
As far as ‘windows of opportunity’ are concerned, when an effective drug-free option to address overweight and obesity is available, medical professionals' duty of care to their patients should be such as to give them pause for thought before reaching for the prescription pad