GLP-1s Increase Risk Of Osteoporosis And Gout; Novo Nordisk Failed To Report Deaths To FDA

A new research study on GLP-1 weight loss and diabetes drugs has found an increased risk of osteoporosis and gout. There was a 30% higher chance of osteoporosis and a 100% higher chance of osteomalacia for GLP-1 users compared to non-users. There was also a 12% higher risk of gout for GLP-1 users.

Researchers conducted the observational study by analyzing five years of medical records from over 146,000 adults with obesity and/or Type 2 diabetes. The study has not yet been peer-reviewed, and it cannot prove causality, but it does align with the findings of other research and the warning labels for popular GLP-1 drugs like Ozempic and Wegovy.

Researchers have been trying to figure out why the drugs may lead to bone loss. It could be due to a lack of nutrients, such as vitamin D and protein, because the GLP-1 drugs significantly reduce appetite. Another hypothesis is that the bones are adapting to the reduced weight, similar to the way an astronaut loses bone density after living in a zero-gravity environment for a period of time.

GLP-1 advocates state that bone loss can be mitigated with a high-protein diet with weight-bearing exercises alongside the use of the drug. The diet and exercise regimen suggested is also the same advice people would give for losing weight naturally without using GLP-1 drugs.

A review published on March 4 in eClinicalMedicine found that 60% of weight was regained by adult users after 1 year of GLP-1 cessation, with an estimated plateau of weight regain at 75%.

“Our projections show that even though people regain most of the weight they have lost, they still maintain some of the weight loss, but what we currently don’t know is if the same proportion of lean mass is recovered,” Lead Author Brajan Budini said. “If the regained weight is disproportionately fat, individuals may ultimately be worse off than before in their fat-to-lean mass ratio, which may have adverse consequences for their health.”

As a result of this data, some health care professionals are saying users who successfully lose weight on GLP-1s may need to keep taking the drugs for the rest of their lives to keep the weight off. Obesity was first classified as a chronic disease by the American Medical Association (AMA) in 2013. Susan Wolver, the medical director at VCU Health’s Medical Weight Loss Program, said, “Obesity is a chronic, progressive, and relapsing disease. Nobody would ever put someone on blood pressure medicine and say, ‘OK, your blood pressure is really well controlled now, let’s take away the medicine and see what happens.’”

There is no safety data to understand the potential side effects of taking GLP-1 drugs for 5 or 10+ years.

D.L. Katz warned about the classification of obesity as a disease in a Nature article in 2014, stating “The categorization of obesity as a disease could have a pernicious influence on efforts to remedy the problem at its true origins. The treatment of diseases customarily involves drugs, medical technology, clinic visits, and surgical procedures. If obesity is a disease, the therapeutic advances on which its management depends presumably reside in these domains.”

Katz warned about dependence on drugs to treat a condition that was recently classified as a disease, but has external factors that are contributing to its proliferation. Now, one in eight Americans are currently taking GLP-1 drugs, and nearly one in five has taken the drugs at some point.

The Trump administration has worked to reduce the prices of GLP-1 drugs to make them more accessible. Secretary Kennedy said this is a “tool in the toolkit” to address obesity, while the updated food guidelines are one step to addressing the underlying causes of the obesity epidemic in America.

FDA Warns Novo Nordisk

The FDA issued a warning letter to Novo Nordisk, the manufacturer of Ozempic and Wegovy, for failing to follow postmarketing adverse drug experience (PADE) regulations. According to the letter, the company failed to disclose two deaths, and another death was submitted late, and only after it was discussed during an FDA inspection.

The FDA is not claiming that the three deaths were caused by the GLP-1 drugs, but that the company violated PADE regulations by not promptly submitting serious adverse effects that are potentially connected to use of their drugs.

One of the deaths of a man who took semaglutide was not reported by the company because they could not find a patient identifier, which the FDA found in the source documents. Another death of a patient who received semaglutide was not reported to the FDA because the reporter was not a health care professional. Cases of death must be reported to the FDA, even if not by a health care professional.

The third case involved a patient who was feeling depressed and committed suicided. Novo Nordisk did not seek additional information from the reporting physician, including patient identifiers, and did not report the death to the FDA.

Suicidal ideation has been a concern with GLP-1 usage and was previously listed on warning labels for semaglutide products like Wegovy. The FDA issued an update in January and found there was not enough information to establish a causal link between the drugs and suicidal ideation. The drug labels have since been updated to no longer include a warning for suicidal ideation.

Other serious side effects have been linked to GLP-1s, as previously reported by The HighWire, including gastroparesis and blindness. Non-arteritic anterior ischemic optic neuropathy (NAION) is the second-highest category for lawsuits against GLP-1 manufacturers, behind gastroparesis.