‘It’s time for some drastic measures to bring down his weight…’ says the doctor in the trailer for South Park: The End of Obesity.
STAT on Novo Nordisk to test GLP-1 drugs for people with alcohol-associated liver disease.
The Hill on Senate Health Committee Chair Bernie Sanders stating Wegovy could bankrupt US health system.
JAMA on bariatric surgery protection against development of breast cancer.
STAT on pharmaceutical giant Roche’s recent acquisition of experimental obesity medication CT-388; a GLP-1/GIP target.
Nature Medicine on four-year weight loss trajectory for patients on semaglutide, to 11.7% versus 1.5% for the placebo group.
NEWS
STAT on Novo Nordisk to test whether its GLP-1 drugs can help people with alcohol-associated liver disease.
The study will try three drugs: NNC0194-0499, cagrilintide, and semaglutide alone or in combinations, on liver damage and alcohol use in people with alcohol-related liver disease, over 39 weeks.
The drug NNC0194-0499 targets a liver hormone, FGF-21, while cagrilintide is a dual amylin and calcitonin receptor agonist; which when combined with semagltude is imaginatively known as CagriSema.
The main outcome measure is ’change in enhanced liver fibrosis’ measured through a blood test.
The study will recruit 240 patients, with a schedule to complete in September 2025.
Beyond the current state, we are destined to see more combination therapies abound, just as we have for the care of cancer patients with multiple chemotherapy agents.
Eli Lilly and Company filed lawsuits in September and October 2023 and has now has entered into a settlement agreement requiring defendant Totality Medispa to make a monetary payment and prohibiting Totality from engaging in certain conduct.
This ‘…will stop Totality Medispa from misleading consumers into believing that this med spa is selling Mounjaro or Zepbound approved by the FDA, that its compounded products have been the subject of clinical tests, or that its compounded medicines have been proven safe and effective to achieve certain clinical results.’
In addition, the ‘…settlement agreement requires Totality Medispa to make a monetary payment and to take several corrective actions.’
STAT reports on pharmaceutical giant Roche’s recent acquisition of experimental obesity medication CT-388; a GLP-1/GIP target.
The once-weekly injectable drug resulted in an average placebo-adjusted weight loss of 18.8% after 24 weeks, in a phase 1b study.
96 patients were scheduled to be recruited, though the actual number is not reported.
More impressive is at week 24, 100% of CT-388 treated participants achieved a weight loss of >5%, 85% achieved >10%, 70% achieved >15%, and 45% achieved >20%.
Levi Garraway, Roche’s chief medical officer said ‘…We are very pleased to see the significant and clinically meaningful weight loss in people treated with CT-388.’
The drug CT-388 was acquired through Roche’s purchase of Carmot Therapeutics for $2.7 billion upfront.
OPINION
The Hill on Senate Health Committee Chair Bernie Sanders stating Wegovy could bankrupt US health system.
The staff report states ‘…Pricing drugs based on their value cannot serve as a blank check…’ and ‘…important as these drugs are, they will not do any good for the millions of patients who cannot afford them.’
The report notes ‘…If half of American adults with obesity took Wegovy and the other new weight loss drugs, it could cost the health care system $411 billion per year — more than total spending for all retail prescription drugs in 2022.’
I get this, but total spending in terms of direct medical costs related to obesity were $480B in 2019, and indirect losses from employee productivity totaled $1.2Tr – so we need to also consider the potential savings, as well as the costs incurred.
Doh!
‘It’s time for some drastic measures to bring down his weight…’ says the doctor in the trailer for South Park: The End of Obesity.
With a new episode to be released on May 24, Stan’s dad Randy explains ‘…there’s these new crazy drugs people are doing…’ followed by the doctor asking ‘…Have you’ve heard of semaglutides?’
I guess this is not going to be politically correct, but rather offensive and controversial – past South Park episodes have taken aim at Catholics, gender reassignment, pedophilia, homophobia, Mormons, and many more.
The Times newspaper in the UK reports from the European Congress on Obesity this past week that ‘…Millions of us are going to end up on weight-loss injections…’ and that ‘…the jabs don’t work for one in three adults.’
In addition, one in six people pulled out of the semaglutide trail, from intolerable side effects like nausea.
Nonetheless, Novo Nordisk is valued at over $570 billion, related to the current and potential impacts on numerous chronic diseases, from heart attacks and stroke, to diabetes, and 32 types of cancer.
DATA
Donna Ryan and colleagues publish in Nature Medicine on long-term weight loss for patients on semaglutide, sustained through to four years, at 11.7% versus 1.5% for the placebo group.
The weight-loss trajectory continued to week 65 and then was sustained for the study period through week 208, or four years.
At two years, two thirds of patients on semaglutide had lost greater than 5% of total body weight; whilst positive, this also means one-third had not lost 5%, considered to be non-responders – that is a large number on an expensive drug.
Indeed, 21% or one-in-five patients on placebo managed to achieve 5% total weight loss – at a much lesser cost than the price of the GLP-1 med.
In addition, 52.4% of patients treated with semaglutide achieved improvement in BMI category compared with 15.7% of those receiving placebo.
I laud this publication, and the advancements in drug development, but I also want to call out the impact of placebo with lifestyle counselling… impressive, worthwhile and relevant.
Dr. Ted Kyle at ConscientHealth reports on two studies from the European Congress on Obesity in Vienna this week.
He states ‘…Tailoring and tapering the dosing of obesity medicines to individual patient needs can produce good results…’ such that individual patient needs vary.
These are data from the Embla digital health platform for obesity care and are ‘…a welcome reminder. Obesity care is not a one-size-fits-all endeavor.’
An additional abstract published at ECO reviewed over four million people in Sweden, with 332,501 cancer cases recorded over a period of abut 25 years.
Many of the cancers were related to obesity, inclusive of head and neck cancers, gastrointestinal tract cancers, melanoma, genital cancers, several endocrine cancers, connective tissue cancer, and hematological cancers.
Of note, a higher BMI of 5kg/m2 raised the possibility of potential obesity-related cancers by 17% in men and 13% in women.
MedPage Today publishes on a supported exercise intervention that helps Black women with obesity shed weight.
The pilot program cut HbA1c, boosted functional mobility, and fostered camaraderie, as per Henri Parson, PhD, of Eastern Virginia Medical School in Norfolk.
At 24 weeks, HbA1c dropped by 0.17%, weight by 12 pounds, from 27 women who had completed the program.
This data is highly preliminary, on a very small number of patients.
From the Journal of the American Medical Association, in almost 600 men with obesity in the UK, text messaging with behavioral messaging combined with a financial incentive led to almost 5% total weight loss at 12 months, compared to 3% for text messaging alone, versus just 1% for the control group.
The aptly named The Game of Stones clinical trial [a stone is fourteen pounds and commonly used as a measure of weight in the UK], intervened with financial incentives of £400 (US $490) that was placed in a study account to access at the end of the clinical trial, but that money would be lost if weight loss goals were not attained.
The goals were 5% weight loss from baseline at 3 months (£50 [$64] secured), 10% from baseline at 6 months (£150 [$191] secured), and maintaining 10% weight loss at 12 months (£200 [$254] secured).
If all goals were met, participants could retain £400 [$490].
The authors findings ‘…support text messaging combined with financial incentives to attain weight loss in men with obesity.’
I have two takeaways – which patients are most likely to respond to this approach, and second, how can we incorporate this approach to augment the outcomes for patients on medication or surgical interventions for obesity?
Ted Kyle has an additional commentary – ‘…Can we imagine that researchers would give cancer patients cash incentives for shrinking their tumors – while witholding medical therapy known to be more effective than the force of will? Nope.’
From JAMA, bariatric surgery may protect against development of breast cancer.
In a study of almost 3,000 women over 24 years, there was a 32% decreased risk of breast cancer was observed in the bariatric surgery group, compared to women who underwent usual obesity care.
In addition, those women who had higher baseline insulin levels, had a risk reduction of over 50% in rates of breast cancer.
Why is this so?
Well, the biological mechanisms by which bariatric surgery may reduce breast cancer risk are unknown.
If I was Eli Lilly or Novo Nordisk, or the host of other companies in the GLP-1 space, I would be planning to monitor my clinical trial patients for the next twenty years – the results are likely to be similar to the above in terms of reduction in breast cancer rates.
