Lawsuit could challenge trust in Ozempic and other popular weight loss drugs (Jun 2024, Wegovy, Rybelsus, semaglutide) [Collection of info] Article

[Michael Harrop]

https://medicalxpress.com/news/2024-06-lawsuit-ozempic-popular-weight-loss.html

Dozens of patients who suffered gastrointestinal problems after taking these drugs brought lawsuits alleging that these companies failed to properly warn patients about the risks.

Click to shrink...

These drugs make people feel full. Doctors started prescribing them for weight management even before the FDA approved them for that purpose. This is a practice known as off-label prescribing. Off-label prescribing is legal and accounts for more than 20% of prescribing activity in the United States.

Click to shrink...

Novo Nordisk has also made a mint on weight loss drugs. Its sales of Ozempic, Wegovy and Rybelsus have made it the most valuable company by market capitalization in Europe. It is currently more valuable than companies such as Tesla and Visa and has been described by one reporter as the "single company propping up" the entire Danish economy.

Click to shrink...

The lawsuit consolidates dozens of cases brought by patients who took one of these five drugs. They were consolidated partly because the legal grounds for all these cases were similar. The trial is happening in Pennsylvania because that was the state with the most pending legal actions. Also, Novo Nordisk's U.S. headquarters are located nearby in New Jersey.

Click to shrink...

For the past decade, however, the FDA's credibility has been under attack. Conspiracy theories about the agency abound on social media. The FDA is often the target of baseless accusations that it approves harmful drugs and suppresses good ones.

Click to shrink...

From Wikipedia:

Semaglutide is an antidiabetic medication used for the treatment of type 2 diabetes and an anti-obesity medication used for long-term weight management. It is a peptide similar to the hormone glucagon-like peptide-1 (GLP-1), modified with a side chain. It can be administered by subcutaneous injection or taken orally.

It is sold under the brand names Ozempic and Rybelsus for diabetes, and under the brand name Wegovy for weight loss.

Semaglutide is a glucagon-like peptide-1 receptor agonist.

Click to shrink...

 

[Michael Harrop]

The NYT has a much more enthusiastic take on these drugs:

The Promise of Weight-Loss Drugs. Where these drugs might take us — and what that means for medicine.
https://www.nytimes.com/2024/06/24/briefing/ozempic-weight-loss-drugs.html

Scientists believe the drugs are about to revolutionize several fields of medicine, such as cardiology and endocrinology. Researchers are also running dozens of trials to see whether they might help with Alzheimer’s, liver disease, polycystic ovary syndrome and even skin conditions. If these trials prove successful, the drugs may extend many lives by years, save billions in medical costs and divide public health into before-and-after epochs. A researcher studying these drugs told me he felt like the scientist who first discovered antibiotics.

These drugs, called GLP-1s (glucagon-like peptide 1 receptor agonists), mystify even the scientists who study them. When I asked researchers how it was possible that Ozempic might help with cognitive issues and nonalcoholic fatty liver disease and opioid addiction, they gave the same answer: We don’t know!

Ozempic and drugs like it are considered “forever drugs” — that is, people are supposed to stay on them for the rest of their lives. They’re like statins or blood pressure medications. When you stop taking them, they stop working.

These medicines are incredibly expensive. One state stopped covering some of them this year.

Click to shrink...

 

[Michael Harrop]

Study links Ozempic to higher risk of eye condition that can cause vision loss https://www.statnews.com/2024/07/03/ozempic-wegovy-naion-vision-loss-study/

Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide (Jul 2024, n=16 827) https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2820255

a potential link between Novo Nordisk’s GLP-1 drugs Ozempic and Wegovy and an eye condition that can cause vision loss

semaglutide (the scientific name of both drugs).

After hearing anecdotes of patients on the diabetes and obesity drugs experiencing nonarteritic anterior ischemic optic neuropathy, or NAION, researchers at Massachusetts Eye and Ear analyzed data from a registry of patients at their institution to see if there was a broad trend.

the researchers estimate that there was a 4.28 times greater risk of developing the condition in patients prescribed semaglutide

Click to shrink...

Key Points​

Question Are prescriptions for semaglutide associated with an increased risk of nonarteritic anterior ischemic optic neuropathy (NAION) in patients with type 2 diabetes or patients who are overweight or obese?

Findings This matched cohort study of 16 827 patients revealed higher risk of NAION in patients prescribed semaglutide compared with patients prescribed non–glucagon-like peptide receptor agonist medications for diabetes or obesity.

Meaning The findings suggest a potential risk of NAION associated with prescriptions for semaglutide, but future study is required to assess causality.

Click to shrink...

Abstract​

Importance Anecdotal experience raised the possibility that semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA) with rapidly increasing use, is associated with nonarteritic anterior ischemic optic neuropathy (NAION).

Objective To investigate whether there is an association between semaglutide and risk of NAION.

Design, Setting, and Participants In a retrospective matched cohort study using data from a centralized data registry of patients evaluated by neuro-ophthalmologists at 1 academic institution from December 1, 2017, through November 30, 2023, a search for International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code H47.01 (ischemic optic neuropathy) and text search yielded 16 827 patients with no history of NAION. Propensity matching was used to assess whether prescribed semaglutide was associated with NAION in patients with type 2 diabetes (T2D) or overweight/obesity, in each case accounting for covarying factors (sex, age, systemic hypertension, T2D, obstructive sleep apnea, obesity, hyperlipidemia, and coronary artery disease) and contraindications for use of semaglutide. The cumulative incidence of NAION was determined with the Kaplan-Meier method and a Cox proportional hazards regression model adjusted for potential confounding comorbidities. Data were analyzed from December 1, 2017, through November 30, 2023.

Exposures Prescriptions for semaglutide vs non–GLP-1 RA medications to manage either T2D or weight.

Main Outcomes and Measures Cumulative incidence and hazard ratio of NAION.

Results Among 16 827 patients, 710 had T2D (194 prescribed semaglutide; 516 prescribed non–GLP-1 RA antidiabetic medications; median [IQR] age, 59 [49-68] years; 369 [52%] female) and 979 were overweight or obese (361 prescribed semaglutide; 618 prescribed non–GLP-1 RA weight-loss medications; median [IQR] age, 47 [32-59] years; 708 [72%] female). In the population with T2D, 17 NAION events occurred in patients prescribed semaglutide vs 6 in the non–GLP-1 RA antidiabetes cohort. The cumulative incidence of NAION for the semaglutide and non–GLP-1 RA cohorts over 36 months was 8.9% (95% CI, 4.5%-13.1%) and 1.8% (95% CI, 0%-3.5%), respectively. A Cox proportional hazards regression model showed higher risk of NAION for patients receiving semaglutide (hazard ratio

---

, 4.28; 95% CI, 1.62-11.29); P < .001). In the population of patients who were overweight or obese, 20 NAION events occurred in the prescribed semaglutide cohort vs 3 in the non–GLP-1 RA cohort. The cumulative incidence of NAION for the semaglutide vs non–GLP-1 RA cohorts over 36 months was 6.7% (95% CI, 3.6%-9.7%) and 0.8% (95% CI, 0%-1.8%), respectively. A Cox proportional hazards regression model showed a higher risk of NAION for patients prescribed semaglutide (HR, 7.64; 95% CI, 2.21-26.36; P < .001).

Conclusions and Relevance This study’s findings suggest an association between semaglutide and NAION. As this was an observational study, future study is required to assess causality.

Click to shrink...

---

 

[Michael Harrop]

GLP-1 medications such as Ozempic and Wegovy may help lower the risk of certain cancers https://www.cnn.com/2024/07/05/health/glp-1-weight-loss-lower-cancer-risk/index.html

People who are overweight or obese have a higher risk of getting 13 types of cancer, and the risk increases the longer a person is overweight and the more excess weight they gain.

But a study published Friday in the journal JAMA Network Open found that people with type 2 diabetes who were being treated with a class of GLP-1 drugs were significantly less likely to be diagnosed with 10 of the 13 obesity-associated cancers than those who were taking insulin.

The risk was cut by more than half for gallbladder cancer, meningioma, pancreatic cancer and hepatocellular carcinoma, a kind of liver cancer. It was also significantly reduced for ovarian cancer, colorectal cancer, multiple myeloma, esophageal cancer, endometrial cancer and kidney cancer.

Click to shrink...

Glucagon-Like Peptide 1 Receptor Agonists and 13 Obesity-Associated Cancers in Patients With Type 2 Diabetes (Jul 2024, n=1 651 452)

Key Points​

Question Is there clinical evidence supporting the potential benefits of glucagon-like peptide receptor agonists (GLP-1RAs) for the prevention of 13 obesity-associated cancers (OACs)?

Findings This cohort study of more than 1.6 million patients with type 2 diabetes (T2D) who had no prior diagnosis of 13 OACs found that patients with T2D treated with GLP-1RAs vs insulin had a significant risk reduction in 10 of 13 OACs, including esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancer as well as meningioma and multiple myeloma. No decrease in cancer risk was associated with GLP-1RAs compared with metformin.

Meaning This study provides clinical data suggesting that GLP-1RAs may reduce the risk of specific OACs compared with insulins.

Click to shrink...

Abstract​

Importance Thirteen human malignant neoplasms have been identified as obesity-associated cancers (OACs), ie, the presence of excess body fat is associated with increased risk of developing cancer and worse prognosis in patients with these specific tumors. The glucagon-like peptide receptor agonist (GLP-1RA) class of pharmaceuticals are effective agents for the treatment of type 2 diabetes (T2D) and for achieving weight loss, but the association of GLP-1RAs with the incident risk of 13 OACs is unclear.

Objective To compare the incident risk of each of the 13 OACs in patients with T2D who were prescribed GLP-1RAs vs insulins or metformin.

Design, Setting, and Participants This retrospective cohort study was based on a nationwide multicenter database of electronic health records (EHRs) of 113 million US patients. The study population included 1 651 452 patients with T2D who had no prior diagnosis of OACs and were prescribed GLP-1RAs, insulins, or metformin during March 2005 to November 2018. Data analysis was conducted on April 26, 2024.

Exposures Prescription of GLP-1RAs, insulins, or metformin.

Main Outcomes and Measures Incident (first-time) diagnosis of each of the 13 OACs occurring during a 15-year follow-up after the exposure was examined using Cox proportional hazard and Kaplan-Meier survival analyses with censoring applied. Hazard ratios (HRs), cumulative incidences, and 95% CIs were calculated. All models were adjusted for confounders at baseline by propensity-score matching baseline covariates.

Results In the study population of 1 651 452 patients with T2D (mean [SD] age, 59.8 [15.1] years; 827 873 [50.1%] male and 775 687 [47.0%] female participants; 5780 [0.4%] American Indian or Alaska Native, 65 893 [4.0%] Asian, 281 242 [17.0%] Black, 13 707 [0.8%] Native Hawaiian or Other Pacific Islander, and 1 000 780 [60.6%] White participants), GLP-1RAs compared with insulin were associated with a significant risk reduction in 10 of 13 OACs, including in gallbladder cancer (HR, 0.35; 95% CI, 0.15-0.83), meningioma (HR, 0.37; 95% CI, 0.18-0.74), pancreatic cancer (HR, 0.41; 95% CI, 0.33-0.50), hepatocellular carcinoma (HR, 0.47; 95% CI, 0.36-0.61), ovarian cancer (HR, 0.52; 95% CI, 0.03-0.74), colorectal cancer (HR, 0.54; 95% CI, 0.46-0.64), multiple myeloma (HR, 0.59; 95% CI, 0.44-0.77), esophageal cancer (HR, 0.60; 95% CI, 0.42-0.86), endometrial cancer (HR, 0.74; 95% CI, 0.60-0.91), and kidney cancer (HR, 0.76; 95% CI, 0.64-0.91). Although not statistically significant, the HR for stomach cancer was less than 1 among patients who took GLP-1RAs compared with those who took insulin (HR, 0.73; 95% CI, 0.51-1.03). GLP-1RAs were not associated with a reduced risk of postmenopausal breast cancer or thyroid cancer. Of those cancers that showed a decreased risk among patients taking GLP-1RAs compared with those taking insulin, HRs for patients taking GLP-1RAs vs those taking metformin for colorectal and gallbladder cancer were less than 1, but the risk reduction was not statistically significant. Compared with metformin, GLP-1RAs were not associated with a decreased risk of any cancers, but were associated with an increased risk of kidney cancer (HR, 1.54; 95% CI, 1.27-1.87).

Conclusions and Relevance In this study, GLP-1RAs were associated with lower risks of specific types of OACs compared with insulins or metformin in patients with T2D. These findings provide preliminary evidence of the potential benefit of GLP-1RAs for cancer prevention in high-risk populations and support further preclinical and clinical studies for the prevention of certain OACs.

Click to shrink...

 

[Michael Harrop]

Weight Loss Drugs Also Effective for Quitting Smoking https://www.webmd.com/obesity/news/20240730/weight-loss-drugs-also-effective-for-quitting-smoking

Association of Semaglutide With Tobacco Use Disorder in Patients With Type 2 Diabetes: Target Trial Emulation Using Real-World Data (Jul 2024) https://www.acpjournals.org/doi/10.7326/M23-2718

Abstract​

Background:​

Reports of reduced desire to smoke in patients treated with semaglutide, a glucagon-like peptide receptor agonist (GLP-1RA) medication for type 2 diabetes mellitus (T2DM) and obesity, have raised interest about its potential benefit for tobacco use disorders (TUDs).

Objective:​

To examine the association of semaglutide with TUD-related health care measures in patients with comorbid T2DM and TUD.

Design:​

Emulation target trial based on a nationwide population-based database of patient electronic health records.

Setting:​

United States, 1 December 2017 to 31 March 2023.

Participants:​

Seven target trials were emulated among eligible patients with comorbid T2DM and TUD by comparing the new use of semaglutide versus 7 other antidiabetes medications (insulins, metformin, dipeptidyl-peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, sulfonylureas, thiazolidinediones, and other GLP-1RAs).

Measurements:​

The TUD-related health care measures (medical encounter for diagnosis of TUD, smoking cessation medication prescriptions, and smoking cessation counseling) that occurred within a 12-month follow-up were examined using Cox proportional hazards and Kaplan–Meier survival analyses.

Results:​

The study compared 222 942 new users of antidiabetes medications including 5967 of semaglutide. Semaglutide was associated with a significantly lower risk for medical encounters for TUD diagnosis compared with other antidiabetes medications, and was strongest compared with insulins (hazard ratio

---

, 0.68 [95% CI, 0.63 to 0.74]) and weakest but statistically significant compared with other GLP-1RAs (HR, 0.88 [CI, 0.81 to 0.96]). Semaglutide was associated with reduced smoking cessation medication prescriptions and counseling. Similar findings were observed in patients with and without a diagnosis of obesity. For most of the group comparisons, the differences occurred within 30 days of prescription initiation.

Limitation:​

Documentation bias, residual confounding, missing data on current smoking behavior, body mass index, and medication adherence.

Conclusion:​

Semaglutide was associated with lower risks for TUD-related health care measures in patients with comorbid T2DM and TUD compared with other antidiabetes medications including other GLP-1Ras, primarily within 30 days of prescription. These findings suggest the need for clinical trials to evaluate semaglutide’s potential for TUD treatment.

Click to shrink...

---

 

[Michael Harrop]

Ozempic Is Changing People’s Skin, Say Plastic Surgeons. “It becomes like an old, overused rubber band.” https://www.allure.com/story/ozempics-effects-on-skin

These are changes he hasn’t noticed in patients who have lost significant weight in other ways—like through diet or gastric bypass surgery—which makes him think it’s unique to GLP-1 usage.

It’s quite possible that the drug is essentially “turning off the engines that make our skin look healthier and youthful."

One of the country’s top facelift surgeons was the first to bring this to our attention: Julius Few, MD, a board-certified plastic surgeon in Chicago and Beverly Hills

In the months since, I’ve reached out to 15 other board-certified plastic surgeons and dermatologists across the United States for their insights.

Click to shrink...

 

[Michael Harrop]

Ozempic Works Differently Than Previously Thought. Weight loss drugs such as Ozempic, Wegovy and Mounjaro seem to directly impact metabolism, not just appetite https://www.newsweek.com/ozempic-works-differently-thought-1943422

They are associated with side effects, such as poor or slow digestion, nausea, vomiting, bloating, and more—and they only work for as long as people take them, so their effects are not permanent. However, they have been shown to be effective at helping people control their blood sugar levels and lose weight.

Click to shrink...

GLP-1 therapy increases visceral adipose tissue metabolic activity: lessons from a randomized controlled trial in obstructive sleep apnea (Aug 2024, n=30) https://onlinelibrary.wiley.com/doi/10.1002/oby.24126

---

Ozempic Under Fire As Suicidal Thoughts Link Claimed by Controversial Study. TikTok's latest fat-melting "miracle" has come under fire after a new, controversial study linked the weight loss drug to suicidal ideation. https://www.newsweek.com/ozempic-suicidal-thoughts-side-effects-weight-loss-1941853

When used as a weight loss drug, semaglutide has been shown to have some uncomfortable side effects. Most studies into these have focused on gut problems, but increasingly, research is finding associations between semaglutide and adverse psychiatric events, including suicidal thoughts.

Click to shrink...

Psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide: a pharmacovigilance analysis of individual case safety reports submitted to the EudraVigilance database (Jan 2024) https://link.springer.com/article/10.1007/s11096-023-01694-7

Association of semaglutide with risk of suicidal ideation in a real-world cohort (Jan 2024) https://www.nature.com/articles/s41591-023-02672-2

Disproportionality Analysis From World Health Organization Data on Semaglutide, Liraglutide, and Suicidality (Aug 2024) https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2822453

 

[Michael Harrop]

An Obesity Drug Prevents Covid Deaths. People taking Wegovy were not protected from infection. But in a large trial, their death rates were markedly lower, for reasons that are not clear. https://www.nytimes.com/2024/08/30/health/wegovy-covid-deaths.html

As the Covid epidemic erupted, a large clinical trial of Wegovy, sponsored by its maker, Novo Nordisk, was already underway. The goal was to learn whether the drug prevented deaths from heart disease and health events like heart attacks.

The study’s 17,604 participants had heart disease and an average body mass index of 27 or higher. They did not have diabetes. They were followed for more than three years.

A total of 4,258 participants became infected with Covid, nearly equally divided between those taking Wegovy and those taking a placebo. Of those patients, 184 died — 78 of those who had been assigned to take Wegovy and 106 taking a placebo, a significant difference.

The obesity drug also reduced the overall death rate by 19 percent, the researchers reported.

Click to shrink...

The study:
The Effect of Semaglutide on Mortality and COVID-19–Related Deaths: An Analysis From the SELECT Trial (Aug 2024) https://www.jacc.org/doi/10.1016/j.jacc.2024.08.007

Editorial comment:
Semaglutide, COVID-19 Mortality, and the Power of Harnessing Ongoing Clinical Trials During Unexpected Outbreaks https://www.jacc.org/doi/10.1016/j.jacc.2024.08.035

 

[Michael Harrop]

Ozempic, Wegovy, Rybelsus: Are we losing sight of overall health? Here's what the science says

• https://medicalxpress.com/news/2024-09-ozempic-wegovy-rybelsus-sight-health.html
• https://theconversation.com/ozempic-wegovy-rybelsus-are-we-losing-sight-of-overall-health-heres-what-the-science-says-238484

Another great article from The Conversation. They publish good stuff.

The volume of prescriptions and the budget allocated to them by public health insurance schemes are exploding, as are the profits of the companies that manufacture them. Part of the popularity of these drugs owes to social networks, but these are not always the best source for health information.

the drugs treat the effects of Type 2 diabetes and obesity but not their causes

Pharmacological treatment, even if it allows an individual to eat less, does not necessarily mean that person will eat better. Similarly, losing weight does not mean one will become more active or healthier. So these new drugs do not cure Type 2 diabetes or obesity. Nor do they prevent these diseases from developing, although they do help to limit the many complications to which they give rise.

What lessons can we learn?​

The clinical effectiveness of GLP-1/GIP analogs in reducing the complications associated with Type 2 diabetes and obesity is indisputable. However, these drugs are not suitable for everyone, and they are certainly not miracle cures that will make it possible for one to regain health without making any changes to lifestyle or environment.

We must bear in mind that their success, both commercial and medical, is also the result of a failure: that of our societies to prevent these diseases, to promote healthy lifestyles and to develop environments conducive to the health of all.

Click to shrink...

 

[Michael Harrop]

Gynecologist Reveals Ozempic's 'Unexpected' Effects on Your Vagina https://www.newsweek.com/gynecologist-ozempic-vagina-womens-health-weight-loss-1966954

"Additionally, GLP-1 agonists can cause gastrointestinal side effects like nausea, vomiting, and diarrhoea. These symptoms may lead to dehydration, which could further contribute to vaginal dryness and discomfort. The changes in diet and gut microbiome associated with these medications may also indirectly impact the vaginal microbiome due to the gut-vagina axis."

Beyond this, some reports have suggested that Ozempic and other GLP-1-based drugs may impact fertility, with numerous anecdotal cases of women getting pregnant on Ozempic despite using birth control. As with effects on vaginal dryness, doctors believe that these so-called "Ozempic babies" may result from the drug's direct interference with the absorption of oral contraceptives. The subsequent weight loss seen by many on these drugs may also contribute to increased fertility.

Click to shrink...