Why do some people have better weight loss results with Ozempic or Wegovy?

Medical News Today

5 hours ago

Research on weight loss medications, particularly glucagon-like peptide-1 receptor agonists (GLP-1RAs), and why people experience varying results is ongoing.One study helped identify multiple components that may affect successful weight loss among people using GLP-1RAs.The researchers found that taking the medication for longer and starting on semaglutide rather than other GLP-1RA options produced more successful weight loss results.A popular group of weight loss medications is glucagon-like peptide-1 receptor agonists (GLP-1RAs), which include the likes of Ozempic and Wegovy — medications that are used to treat type 2 diabetes and obesity.A study recently published in Diabetes, Obesity and Metabolism explored weight fluctuations among participants after taking GLP-1RAs. The results suggest that factors like taking GLP-1RAs longer, having greater accumulated exposure to GLP-1RAs, using semaglutide, and not having diabetes may make it more likely for some people to experience successful weight loss from GLP-1RA use.What impacts the effectiveness of GLP-1RAs?This research involved a total of 679 participants and was a retrospective cohort study. All participants were overweight or obese, and this was determined by body mass index (BMI). Some participants also had type 2 diabetes. All participants had at least three months' worth of follow-up and at least three noted weight measurements during the follow-up.Researchers had data from participants' follow-up visits, including factors like body composition and measurements of liver and kidney function. Their data looked at treatment with seven different GLP-1RAs, including semaglutide, lixisenatide, and liraglutide.Researchers examined weight fluctuation among participants and divided participants into three groups: successfully losing weight, staying the same weight, or regaining weight. In their analyses, they then further classified participants as having successful or unsuccessful weight reduction. The unsuccessful category included both weight regain and staying the same weight.Researchers did their analyses at three months, six months, and then at one year. The average age of participants was thirty-seven years old, and about 21% of participants had diabetes.Participants who had been on GLP-1RAs for longer were more likely to experience successful weight reduction at six and twelve months. At the three and six-month marks, participants who experienced successful weight reduction were also less likely to have diabetes and more likely to start their treatment on semaglutide.At the three-month follow-up, participants in the weight regain group also had higher estimated glomerular filtration rates, which measures kidney function. This was also true when looking at just participants with prediabetes. The authors note that people with obesity can experience these higher filtration rates, which can then lead to worse kidney function.Researchers also observed that the group that remained stable had higher fasting plasma glucose levels than the other groups and worse beta cell function and insulin resistance than participants who successfully lost weight.Why do some people lose more weight on GLP-1s?In their univariate logistic regression analysis, the researchers identified several factors that may be related to successful weight loss. These included longer time on GLP-1RA treatment, semaglutide use, lower blood sugar levels, and a higher percentage of body fat. They also observed that greater Homeostasis Model Assessment of β-Cell Function levels, which helps to measure beta cell function in the pancreas and insulin resistance, was associated with successful declines in weight. For women, having a lower skeletal muscle mass was also associated with successful weight reduction.After adjusting for age, sex, and BMI, the researchers found that the longer people used GLP-1RAs, the more they lost weight successfully at all the follow-up time points. At three and six months, starting semaglutide, compared to other GLP-1RAs, was linked to successful weight loss.For men, having a body fat percentage greater than 30% was associated with successful weight reduction at three months, but this was not the case for women. At three months, not having diabetes and hemoglobin A1C levels were linked to successful weight loss.In addition to these factors, researchers also observed some non-linear associations. For example, some measurements of muscle mass and basal metabolic rate had a reversed J-shaped association with successful weight loss.Subgroup analyses also revealed that higher accumulated exposure of semaglutide or liraglutide were both associated with successful weight reduction. At three months, liraglutide and semaglutide users with successful weight reduction had higher fasting plasma glucose levels. For men on semaglutide, having a greater percentage of body fat was associated with successful weight loss at a six-month follow-up. Study limitationsThis study does have benefits and potential limitations. Paunel Vukasinov, MD, a dual board-certified Internist and Obesity Medicine Specialist with Medical Offices of Manhattan and contributor to Labfinder.com, who was not involved in the research, noted the following to Medical News Today:'This study offers helpful information about the differences in weight loss results for patients treated with GLP-1 receptor agonists (GLP-1RAs). Clinical trials have shown that GLP-1RAs work well, but this study points out the varied responses in everyday clinical settings. It also tries to find the reasons behind this variability.''However, the lack of randomization, possible confounding factors, and the single-center design do weaken the conclusions. Still, it addresses an important clinical question: why do some patients do well on GLP-1RAs while others stop losing weight or regain it? It encourages us to move toward more personalized obesity care.'— Paunel Vukasinov, MDThis study was conducted among Chinese participants receiving treatment at a single weight loss clinic. Data from other countries may be helpful in future research.Researchers note that only 112 participants had a follow-up assessment at the one-year mark. They also note there was a lack of record for some possible confounding factors and that they weren't able to assess how lifestyle interventions throughout the follow-up could have affected outcomes. Another limiting factor was that 'longitudinal data for body composition was not systematically collected and analyzed at the follow-ups.'Does stopping medication affect results?Treatment discontinuation did happen, which meant differences in medication patterns.When looking specifically at the use of semaglutide and liraglutide in the subgroup analyses, researchers only analyzed the data from the three-month and six-month follow-ups. They were also only able to look at accumulated exposure for two types of GLP-1RAs.Participants without type 2 diabetes had more limited access to GLP-1RAs, and this could have influenced the study's results. One author also noted conflicts of interest.Selena Raines, DO, an osteopathic physician specializing in family medicine and American Osteopathic Association member, who was also not involved in the study, noted the following limits of this study to Medical News Today:'It's important to note the limitations, namely, the small sample size and the even smaller number of participants who continued through the full 12-month follow-up period…This paper does not explore the effects of discontinuation, a crucial aspect given evidence showing significant weight regain in many individuals once GLP-1RAs are stopped, even with continued lifestyle modifications. Nor does it include tirzepatide, which, while not solely a GLP-1RA, currently shows even more promising data for weight loss than semaglutide in existing trials.'More research is required to examine some of the components of the study, such as the differences in weight loss for people with diabetes compared to those without diabetes. More research on how kidney function plays into everything may also be helpful.Weight loss may need a personalized approachThe authors of this study suggest that data from this study could help make the use of GLP-1RAs more precise.It might help improve the success related to these medications. Kais Rona, MD, a bariatric surgeon of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, who was also not involved in the study, noted the following:'Ultimately, this study supports a personalized approach to the use of GLP-1RA medications. One that identifies important physiologic markers prior to the initiation of the treatment regimen, monitors patient response over time, and focuses on long-term success.'The research also highlights the importance of careful clinical oversight when people use GLP-1RAs. 'Many patients are currently receiving these medications from providers outside their primary care home, often without comprehensive management or long-term planning. This raises concerns about suboptimal outcomes and unintended side effects…What we now need are more long-term studies, particularly focused on sustained outcomes, strategies for maintenance after discontinuation, and optimizing individualized care,' Raines said.