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GLP-1 agonists associated with modest weight loss in real-world setting

18th February 2023

The use of glucagon-like peptide-1 (GLP-1) agonists in patients who have type 2 diabetes and are overweight is associated with a small but significant weight loss after 72 weeks, according to a retrospective analysis of electronic health records by US researchers.

It has long been recognised that obesity is an independent risk factor for cardiovascular disease. In addition, cardiovascular disease is often present in those with type 2 diabetes and presents a major cause of death among such patients.

Despite this elevated risk, lifestyle modification, in particular weight loss, has been shown to be associated with better control of diabetes and and a reduction in cardiovascular risk factors.

Clinical trials in overweight, type 2 diabetic patients have demonstrated that drugs such as semaglutide, which is one of the GLP-1 agonists, achieves superior and clinically meaningful reductions in body weight in comparison to placebo.

However, most of the weight loss clinical trials have included a lifestyle intervention to support patients but in the absence of such support, GLP-1 agonist-associated weight loss is no better than that achieved with other agents such as metformin.

In the current study, US researchers from the University of Pittsburgh, wanted to understand the degree to which GLP-1 agonists induced weight loss when used as a part of routine clinical care, i.e. in the absence of a specific behavioural weight loss intervention.

The team retrospectively examined the electronic health records of those prescribed any drugs from the GLP-1 agonist class and the subsequent weight loss after 72 weeks of therapy.

GLP-1 agonists and real-world weight loss

Outcomes were available for 2,405 participants with a mean age of 48 years (47.4% male) and of whom, 92.1% had type 2 diabetes and a mean baseline body mass index of 37.

Only eight weeks after the first dispensing of a GLP-1 agonist, the mean weight loss was 1.1% and this increased to 2.2% after 72 weeks.

However, some patients did even better. For instance, 11.2% had lost at least 5% of their body weight after eight weeks, but after 72 weeks, this proportion increased to just over a third (33.3%).

In fact, at the 72 week mark, nearly half of the entire cohort (42.7%) had lost weight, with a small proportion of patients (10.5%) managing to lose 10% or more of their body weight.

The authors concluded that the use of GLP-1 agonists prescribed at standard doses led to a modest degree of weight loss in a real-world setting and in the absence of any specific patient support.

White GE et al. Real-world weight-loss effectiveness of glucagon-like peptide-1 agonists among patients with type 2 diabetes: A retrospective cohort study. Obesity (Silver Spring) 2023.

Review suggests GLP1 agonists offer similar glycaemic control to bariatric surgery

21st December 2022

A meta-analysis has revealed how GLP1 agonists provide a similar degree of glycaemic control to that achieved following bariatric surgery

Glucagon-like peptide-1 (GLP1) receptor agonists provide the same degree of glycaemic control as that achieved following bariatric surgery but the latter still confers the highest reductions in weight according to a systematic review and meta-analysis by researchers from Ontario, Canada.

According to the World Health Organisation, more than 1 billion people worldwide are obese and the organisation has estimated that by 2025, approximately 167 million people – adults and children – will become less healthy because they are overweight or obese. One particular disease linked to obesity is type 2 diabetes.

Moreover, lifestyle interventions such as a decreased caloric intake and increased physical activity in patients with type 2 diabetes, has been shown to result in a weight loss of 8.6%. An alternative approach to lifestyle modification, in those with type 2 diabetes is bariatric surgery, with 5-year outcome data showing that when combined with medical therapy, surgery was more effective than intensive medical therapy alone at decreasing, or in some cases resolving, hyperglycaemia. GLP1 agonists such as semaglutide have been shown to provide a sustained and clinically relevant reduction in body weight.

Nevertheless, there is a lack of evidence directly comparing GLP1 agonists with bariatric surgery in terms of weight loss and glycaemic control. Consequently, for the present study, the Canadian researchers undertook a systematic review and meta-analysis to directly compare the weight-lowering and glycaemic effect of GLP1 agonists and bariatric surgery in adults with obesity, defined as body mass index (BMI) > 25 kg/m2 in both randomised trial and observational cohort studies.

The primary outcome was the absolute change in weight from baseline to the end of the study period, whereas secondary outcomes were absolute change in body mass index and glycated haemoglobin (HbA1c) in patients with concurrent type 2 diabetes.

GLP1 agonists weight loss and glycaemic control outcomes

A total of 6 studies, both randomised trials and observational studies, with 332 participants were included in the final analysis.

The pooled treatment effect for the change in weight from baseline between bariatric surgery and GLP1 agonists was −22.68 kg (95% CI −31.41 to −13.96) in randomised trials and −25.11 kg (95% CI −40.61 to −9.60) among the observational studies and in both types of study, these results favoured bariatric surgery.

In terms of body mass index, as with overall weight, there was a higher effect from bariatric surgery compared with the GLP1 agonists across all studies. However, the change in glycaemic control (based on HbA1c) levels, based only on randomise trial evidence (due to missing data with the observational studies), was a nonsignificant difference of −1.28% (95% CI −1.94% to −0.61%).

This finding, the authors suggested, indicated that the improvement in glycaemic control achieved from GLP1 agonists may be comparable with metabolic surgery for patients with type 2 diabetes and obesity.

They concluded that among adults with obesity, bariatric surgery, while still providing the greatest level of weight loss conferred similar effects on glycaemic control to GLP1 agonists.

Sarma S et al. Weight loss between glucagon-like peptide-1 receptor agonists and bariatric surgery in adults with obesity: A systematic review and meta-analysis. Obesity (Silver Spring) 2022.