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Scientists react to a conference abstract, presented at the EASD conference in Milan, about a phase 2 trial of a new weight loss injection, CBL-514, and levels of subcutaneous and visceral fat.
Prof Justin Rochford, Chair in Diabetes, Lipodystrophy and Metabolism, Rowett Institute, University of Aberdeen, said:
“We know that having extra fat tissue, especially around the organs inside the body (called visceral fat) is linked to diseases such as diabetes and heart disease. Losing weight lowers the risk of these conditions. Current GLP-1 weight loss drugs mainly work by reducing hunger and so how much we eat. This new drug, CBL-514 takes a different approach and aims to get rid of the fat cells that make up fat tissue by making them self-destruct. One key limitation of GLP-1 drugs is that when people stop taking them, they regain the weight. This study indicates that giving CBL-514 might keep weight off that was lost when taking a GLP-1 drug. At least some of this was by reducing the fat around internal organs.
“This all sounds really positive but there are some important limitations. CBL-514 reduces body fat but is that always good? We know that in rare conditions where healthy body fat is lost, called lipodystrophies, this can lead to diabetes and cardiovascular disease. This is because the fat which should be stored in fat tissue gets shifted to other organs, especially the liver, causing problems. It will be very important to show what happens to fat in the liver, circulating fats in the blood and the body’s ability to control blood sugar levels with CBL-514 treatment. This could particularly be a concern because CBL-514 also reduces fat under the skin, which we know can be a healthy fat store in the body. The study is also quite small and doesn’t say whether men or women were studied nor how many in each experimental group. We know that biological sex affects the build-up of body fat and the effects on health so testing men and women separately will also be important.
“One interesting aspect is that this might be useful alongside or after taking GLP-1 based drugs – however, the GLP-1 part of the study (using tirzepatide) was in rats not humans. The human data used MRI scans to determine that fat around the organs was reduced by the CBL-514 treatment. This adds to previous reports from the company showing a reduction in fat under the skin.
“As is usual for a conference abstract, details of the study overall are quite limited. Also, the placebo group are gaining weight and fat volume. This will accentuate the apparent effect of weight loss with the CBL-514. However, to be fair to the authors this is made clear and this could mimic individuals gaining weight after coming off GLP-1 drugs.
“CL-514 was initially developed to kill off fat cells in unusual fatty lumps under the skin, called lipomas. These can be painful and unsightly. Previous studies by the makers of CL-514 have shown the drug may be useful and safe for this purpose. If it can also be used to get rid of unhealthy fat around the organs in overweight people, this could be really valuable. However, to be a useful obesity therapy it will be critical to show that this doesn’t increase the risk of fat accumulation in other organs or poorer control of blood fat and sugar levels.”
Dr Marie Spreckley, Weight Management Researcher, Prevention of Diabetes and Related Metabolic Disorders in High Risk Groups, Institute of Metabolic Science, University of Cambridge, said:
“These results provide encouraging early evidence that CBL-514 can reduce visceral-fat volume in the abdominal region assessed at the level of the second and third lumbar vertebrae (L2-L3). The placebo comparison and MRI measurements are strengths, and statistically significant differences between the treatment groups were reported at both follow-up assessments. This is an interesting approach, and the results support further research.
“These human findings do not establish whether the treatment helps people lose weight or improves their health. In rats, adding CBL-514 to tirzepatide reduced weight regain after tirzepatide was stopped. This provides a reason to investigate whether CBL-514 could help people maintain weight loss, but, as the press release acknowledges, that benefit remains to be demonstrated in people.
“This is a small subgroup analysis from two phase 2 studies, presented at a conference, with no full journal paper available for this analysis. Follow-up extended to 8-12 weeks after the final treatment. The press release reports mostly mild-to-moderate, transient injection-site reactions and no serious adverse events, which is reassuring at this stage, although longer-term safety remains uncertain.
“Larger trials with longer follow-up will be important to establish whether the fat reduction lasts and whether it leads to improvements in health.”
Abstract title: ‘CBL-514, a First-in-Class Adipocyte Apoptosis-Inducing Injection, Reduces MRI-Measured L2-L3 Visceral Adipose Tissue: Translational Evidence from Preclinical Models to a Phase 2 Clinical Trial’ by Yu-Fang Ling et al. was presented at the European Association for the Study of Diabetes (EASD) conference in Milan.
There is no full paper.
Declared interests
Prof Justin Rochford: “For COI declarations, I am:
Co-inventor on a patent for using AAV-mediated gene therapy to rescue fat development in lipodystrophies (syndromes of fat loss driving metabolic disease).
Involved in two projects funded by pharma companies examining a novel target for obesity therapy.
An SAB member for lipodystrophy United, the US lipodystrophy patients’ organisation.
A member of the Executive Board of the European Consortium for the study of Lipodystrophies (ECLip).
I have previously accepted travel support to attend a lipodystrophy meeting organised by Chiesi, the company providing Metreleptin as a lipodystrophy treatment.”
Dr Marie Spreckley: “Dr Marie Spreckley is a postdoctoral researcher at IMS Epidemiology, University of Cambridge, where her research focuses on nutrition and weight management. She has no financial relationships with food or beverage companies, pharmaceutical companies, or other commercial organisations, and has received no industry funding for her research.”
For all other experts, no reply to our request for DOIs was received.