There has been a lot of noise in the media about weight-loss medications recently. A lot of the coverage has been positive, highlighting the unprecedented safety and effectiveness of new pharmacological weight-loss treatments. However, as is often the case, negative commentary appears to generate more interest, with sceptics questioning whether something as simple as a weekly injection can address a condition as complex as obesity. And the truth is, it’s a fair question.
Originally developed as drugs for type 2 diabetes, GLP-1s lower blood sugar levels by stimulating insulin release, slowing digestion and lowering the secretion of glucagon (glucose) into the bloodstream [1]. However, during the medication’s testing phase, it became clear that patients weren’t just treating their diabetes — they were also losing a significant amount of weight.
After further investigation, scientists were able to explain why. In addition to the physiological effect of slowing digestion, which helps people feel full for longer, GLP-1s also affect patients on a neurological level. Namely, they suppress a person’s appetite by modifying neural pathways involved in reward, motivation and addiction [2]. But to what extent can standalone GLP-1 interventions address overweight and obesity? Let’s dive into it.
How effective are GLP-1s for weight loss, according to clinical trials?
Randomised controlled trials have consistently demonstrated the effectiveness of GLP-1s in inducing weight loss among non-diabetic populations. Two of the topic’s earliest investigations reported roughly 7% mean weight loss for patients who received daily GLP-1 therapy for a year [3] [4]. However, in both of these trials, treatment cohorts had already lost a significant amount of weight during the study run-in period when patients received standardised lifestyle counselling. To generate clearer findings of the medication’s efficacy, the 2015 Novo Nordisk SCALE trial investigated the effects of treating patients with GLP-1s and standardised behavioural therapy simultaneously (without a run-in period). After 56 weeks, patients who received daily high-dose injections of a GLP-1 drug lost an average of 8% (8.4kg) of their body weight compared to those from the control group who lost an average of 2.6% (2.8kg). Weight loss in the control group was attributable to the ‘standardised lifestyle counselling’, which both groups (treatment and control) received ‘approximately monthly’ [5].
Although some dropped more weight than others (14% of treatment group patients actually lost over 15% of their body weight), the drug was found to be effective across a wide variety of people. Nearly ⅔ of GLP-1 patients lost at least 5% of their body weight and outcomes weren’t significantly affected by one’s pre-diabetes status.
The treatment group recorded significantly more weight loss than the control group across multiple cardiometabolic biomarkers, including blood pressure and blood lipid levels. The group also responded positively when surveyed on improvements to their overall quality of life.
Although all of the above-mentioned studies combined GLP-1 therapy with some form of lifestyle counselling, in each case the latter was described as ‘standardised’ and infrequent, and can therefore be assumed to have been very much secondary to the medication. Consequently, the conclusion that can be derived from these trials is that largely standalone GLP-1 treatment appears to be effective in inducing weight loss.
Are GLP-1s safe?
Randomised controlled trials have also consistently found GLP-1s to possess a high safety profile [5] [6] [7] [8]. Although most patients experience side effects, the vast majority of these events are transient and mild to moderate in severity, such as nausea, vomiting and diarrhoea. Moreover, these symptoms can be minimised and sometimes avoided with the support of a high-quality care team.
As is the case with any prescription medication, GLP-1s carry a risk of developing more serious side effects, including pancreatitis, gallbladder issues and ileus. However, the literature clearly indicates that this risk is very small. For example, in the 2015 study, while 6.2% of treatment patients experienced serious adverse events, so too did 5% of patients in the control group. This figure from the control group highlights the significant health risk of living with obesity, which is an important consideration in the context of GLP-1 safety. Despite all this knowledge, no provider of GLP-1s can responsibly prescribe the medication without conducting individualised assessments to guide patient counselling on the risks of GLP-1 treatment.
But what happens when we look at weight management more holistically?
Lasting weight loss needs a holistic approach
The above-discussed trials demonstrated the efficacy of largely standalone GLP-1 therapy in inducing weight loss. Although trial participants received some form of lifestyle counselling, these were standardised, adjunct interventions that complemented the GLP-1 therapy rather than forming an integral part of a personalised, holistic weight-loss programme. In general, the level of guidance and support that patients receive in clinical trials doesn’t accurately reflect the experience they would have at a quality real-world weight-loss service.
We consider these limitations to be the key reasons Eucalyptus patients have experienced superior weight-loss outcomes to clinical trial participants. Whereas participants in Novo Nordisk’s SCALE trial lost less than 9% of their body weight in 56 weeks [4], a cohort of patients on a holistic weight-loss program provided by Juniper lost an average of 11.6% in 32 weeks, using the same medication [10]. The magnitude of this discrepancy might surprise you, but its explanation couldn’t be more straightforward.
We’ve known for decades that a good diet and exercise are two of the most significant factors in weight regulation, but we also know that one-size-fits-all models have limited success [11] [12]. Moreover, we know that complex, chronic conditions like obesity can only be effectively managed by quality multidisciplinary care teams — teams that are both coordinated and responsive to the challenges chronic disease patients typically face during the early stages of a new intervention.
Eucalyptus believes weight-loss programs should be holistic and underpinned by science, safety and exceptional multidisciplinary care continuity. Such programs have been shown to significantly outperform comparable GLP-1-only clinical trial interventions.
References
[1] Tran, K., Park, Y., Pandya, S., et al. (2017) Overview of glucagon-like peptide-1 receptor agonists for the treatment of patients with type 2 diabetes. American Health & Drug Benefits, 10(4), 178-188.
[2] Müller, T., Finan, B., Bloom, S., et al. (2019) Glucagon-like peptide 1 (GLP-1), Mol Metab, 30:72-130.
[3] Astrup, A., Carraro, R., Finer, N., et al. (2012). Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liragltuide. Int J Obes, 36: 843-854.
[4] Wadden, T., Hollander, P., Klein, S., et al. (2013). Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE maintenance randomised study. Int J Obesity, 37: 1443-1451.
[5] Pi-Sunyer, X., Astrup, A., Fujioka, K., et al. (2015) A randomised, controlled trial of 3.0mg of Liraglutide in weight management. N Engl J Med, 373:11-12
[6] Ibid
[7] Rubino, D., Abrahamsson, N., Davies, M., et al. (2021). Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity. JAMA, 325(14): 1414-1425.
[8] Frías, J., Davies, M., Rosenstock, J., et al. (2021). Tirzepatide versus Semaglutide once weekly in Patients with Type 2 Diabetes, N Eng J Med, 385:503-515.
[9] Wilding, J., Batterham, R., Calanna, S., et al. (2021). Once-weekly Semaglutide in adults with overweight or obesity. N Engl J Med, 384: 989-1002.
[10] Talay et al, ‘A retrospective analysis of the effectiveness of an asynchronous weight loss programme using liraglutide 3mg daily combined with behavioural interventions: a real-world evidence study in Australia’ (2023), pre-publication study.
[11] Zeevi, D., Korem, T., Zmora, N., et al. (2015). Personalised nutrition by prediction of glycaemic responses. Cell, 163: 1079-1094.
[12] Price, N., Magis, A., Earls, J., et al. (2017). A wellness study of 108 individuals using personal, dense, dynamic data clouds. Nature biotechnology, 35:747-756
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