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.

Citation
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.

Vaccination protects overweight and obese against severe COVID-19 and death

12th July 2022

Overweight and obese patients protection against severe disease and death when infected with COVID-19 is similar to those of a healthy weight

Both overweight and obese patients who have been vaccinated against COVID-19 have a similar degree of protection against severe disease and death as those of a healthy weight according to a large, population-based cohort study by researchers from the UK and Spain.

Since the start of the COVID-19 pandemic, considerable evidence has emerged indicating how obesity is a risk factor for more severe disease. For example, in a 2020 systematic review of 24 retrospective cohort studies, the odds ratio for intensive care unit admission for obese patients was 1.21 and higher still, for invasive mechanical ventilation (OR = 2.05).

With the widespread introduction of COVID-19 vaccines, it is necessary to understand how overweight and obese patients respond to vaccination. This is especially important in light of evidence showing that despite generating a robust serological response, vaccinated obese adults are twice as likely to develop influenza and influenza-like illness compared with healthy weight adults.

Furthermore, another study found that CD4(+) and CD8(+) T cells from overweight and obese individuals expressed lower levels of CD69, CD28, CD40 ligand, and interleukin-12 receptor, compared with healthy weight and which may contribute to the increased morbidity and mortality from H1N1 influenza A virus.

Despite the concern that overweight and obese patients may not produce a satisfactory immune response to vaccination, there are limited data on the association between body mass index (BMI) and COVID-19 vaccine effectiveness and the risk of severe COVID-19 outcomes after vaccination.

Using the QResearch database, in the present study, researchers used an anonymised patient data set derived from over 1,700 general practices in England and collated demographic and clinical data. They linked this information with the NHS Digital database of positive COVID-19 tests, hospital episode statistics and death certificates.

Included patients were adults and who had a BMI measurement recorded in their medical records and which were then categorised as underweight (BMI < 18.5), healthy weight (BMI 18.5 – 24.9), overweight (BMI 25 – 29.9) and obese (BMI > 30). They examined vaccine effectiveness across the different weight categories and set the main outcomes of interest as hospitalisation and death.

Overweight and obese patients and severe COVID-19 outcomes

A total of 9,171,524 individuals with a mean age of 52 years (47% male) were included in the analysis. During the period of study there were 566,461 positive tests for COVID-19, 32,808 COVID-19-related hospital admissions and 14,389 COVID-related deaths.

Across the whole cohort, 19.2% were unvaccinated, 3.1% had at least one dose, 52.6% two doses and 25% three doses. Uptake of two or three vaccine doses was more than 80% among those deemed overweight or obese.

At least 14 days after the second vaccine dose, the likelihood (based on the odds ratio, OR) of a COVID-19-related hospitalisation (compared to those who were unvaccinated) was lowest for those who were either overweight (OR = 0.32, 95% CI 0.30 – 0.34) or obese (OR = 0.32, 95% CI 0.30 – 0.34) which was similar to those with a healthy weight (OR = 0.34).

Among those who were underweight, there was a slightly higher risk of hospitalisation (OR = 0.51, 95% CI 0.41 – 0.63). However, the odds of hospitalisation after a third vaccine dose were significantly less and similar for each of the different BMI categories.

In relation to mortality, there was a similar pattern 14 days after the second dose, e.g., underweight individuals (OR = 0.60), healthy weight (OR = 0.30) with overweight and obese individuals having the same odds ratio (OR = 0.26). Mortality was also significantly lower after the third dose though there was more uncertainty given the lower number of cases.

The authors concluded that both overweight and obese patients appear to be equally well protected against severe COVID-19 outcomes as those of a healthy weight although vaccine effectiveness appeared to be less in those classed as underweight.

Citation
Piernas C et al. Associations of BMI with COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination in England: a population-based cohort study Lancet Diabetes Endocrinol 2022