Cigarettes with ultralow nicotine levels are now being called the game-changer in the fight against smoking. If you are having trouble in quitting smoking, then, it is for you, that soon the Biden White House is expected to formally propose a plan that will order cigarette nicotine levels to be reduced, reports The Washington Post. For now though, it has been a failure, as these cigarettes, also known as VLN cigarettes that stands for very low nicotine are only available in 5,100 stores in 26 states. This is a very small fraction of the overall market for cigarettes. The company that makes it, 22nd Century, is struggling not because of the low supply, but also from the advocates who have long believed slashing nicotine levels altogether.

The Advent and ideation

Nicotine is a chemical that is produced naturally from tobacco that makes the cigarette and also keeps people hooked. While it is believed that it makes people alert, and get the "hit" to keep them going, it exposes the users to harmful substances, carcinogens, and increases the risk of heart disease, lung cancer, and other illness.

Ultralow-nicotine cigarettes, like the VLN brand, contain about 95% less nicotine than the regular cigarettes. The idea is quite simple: without the addictive grip of nicotine, smokers will find it easier to quit. Research too has shown some promise. For instance, the studies funded by the National Institute on Drug Abuse revealed that very low nicotine cigarettes reduced addiction potential significantly without having users to increase their smoking frequency. However, the problem is, why would anyone choose for a low-nicotine that does not make them feel the same way, when the high-nicotine cigarette is right next to it, making them feel the same way, with the same alertness, sold at the same price.

“It’s very hard to imagine someone actively choosing to continue to use a low-nicotine product for the same price when a high-nicotine product is right next to it,” said Eric Donny, a Wake Forest University School of Medicine nicotine researcher.

No wonder, the experiment with low nicotine product by Philip Morris' Next cigarettes in the 1980s and Vector Tobacco's Quest brand in the early 2000s, flopped.

FDA's Role in the Push

The Food and Drug Administration (FDA) has supported the development of such products, even allowing VLN cigarettes to be marketed as lower-risk options. However, these products remain a niche market, available in only a fraction of U.S. stores.

Recently, the Biden administration has considered a bold step—mandating a dramatic reduction in nicotine levels for all cigarettes sold in the United States. Supporters believe this move could save millions of lives, while critics, including tobacco companies, warn of potential unintended consequences.

What Could Be The Challenges?

Resistance from Big Tobacco Companies: They could argue that slashing nicotine levels could backfire. Their claim is, smokers will turn to black markets or smoke more to satisfy their cravings, which may lead to greater exposure to harmful substances.

Consumer Reluctance: History is proof to the instances of smokers being hesitant to embrace the low-nicotine products.

Political Hurdle: It may face political roadblocks, as under the Trump administration, plans to cut nicotine were shelved.

Could Low-Nicotine Cigarettes Be The Solution?

Advocates believe that ultralow-nicotine cigarettes could be a game-changer, comparing them to decaf coffee or non-alcoholic beer—products that reduce harm while offering a similar experience.

Some experts warn that a black market for traditional cigarettes could undermine these efforts. They also stress the need for safer alternatives, such as vaping products, to support smokers transitioning away from traditional cigarettes.

Novo Nordisk's next-generation obesity drug CagriSema has delivered greater weight loss than a lower dose of Eli Lilly's tirzepatide in a new late-stage trial. The trial has given giving the Danish drugmaker new evidence for its upcoming weight loss injectable as it competes in the rapidly expanding GLP-1 obesity drug market.

In the Phase 3 REIMAGINE 5 trial, adults with type 2 diabetes receiving CagriSema lost an estimated 12.4% of their body weight after 60 weeks, compared with 9.1% among those receiving 5 mg of tirzepatide, the active ingredient in Lilly's Mounjaro and Zepbound. CagriSema also resulted reduction in HbA1c, a measure of average blood sugar.

However, the trial compared 1 mg/1 mg CagriSema to 5 mg tirzepatide, rather than the highest doses used in obesity treatment. Earlier this year, a separate Phase 3 trial in people with obesity found that CagriSema did not meet its goal against high-dose 15 mg tirzepatide. At 84 weeks, CagriSema resulted in 23% weight loss compared to 25.5% with tirzepatide.

What Is CagriSema?

CagriSema is a once-weekly injection that combines two active ingredients: semaglutide and cagrilintide.

Semaglutide is the active ingredient in Novo's Wegovy and Ozempic. It belongs to the GLP-1 receptor agonist class and helps reduce appetite and food intake. Cagrilintide mimics amylin, a hormone involved in appetite regulation and feelings of fullness. By combining the two medicines, Novo is attempting to produce greater weight loss results.

Unlike Wegovy and Ozempic, however, CagriSema is still investigational. Novo submitted it to the US FDA for weight management in December 2025. The regulatory decision is expected in the fourth quarter of 2026.

Also read: Hundreds Of American GLP-1 Users Sue Novo Nordisk, Eli Lilly Over Vision Loss: What Is NAION?

What Did The New Trial Find?

REIMAGINE 5 is based on adults with type 2 diabetes whose blood sugar was not controlled properly with metformin, an SGLT2 inhibitor or both. After 60 weeks, CagriSema showed 12.4% average weight loss. Tirzepatide 5 mg resulted in 9.1% average weight loss.

CagriSema showed 1.71% HbA1c reduction while tirzepatide resulted in 1.67%.

Novo said the combination was generally well tolerated. Gastrointestinal side effects are among the common adverse effects that were seen with the treatment.

Novo's chief scientific officer Martin Holst Lange called the findings “very encouraging” and said they strengthen the company's confidence in CagriSema's potential.

Also read: Blood Test That Could Detect 50+ Cancers Closer To Approval As FDA Raises No Major Concerns About Its Accuracy

Is CagriSema Better Than Mounjaro Or Zepbound?

The new study establishes that CagriSema outperformed 5 mg tirzepatide for weight loss in this particular population sample with type 2 diabetes.

But tirzepatide is available at substantially higher doses, and the earlier obesity head-to-head trial compared CagriSema with 15 mg tirzepatide, where tirzepatide produced better weight loss results.

Therefore, the company has not declared that CagriSema consistently produces more weight loss than tirzepatide across all trials.

CagriSema is Novo's attempt to move beyond single-pathway GLP-1 treatment by combining GLP-1 and amylin biology. In another new Phase 3 trial, REDEFINE 9, CagriSema produced 21% weight loss after 68 weeks, compared with 2% with placebo, in adults with overweight or obesity.

Hundreds of GLP-1 users in the US are suing drugmakers Novo Nordisk and Eli Lilly, alleging they developed a rare form of sudden vision loss called nonarteritic anterior ischemic optic neuropathy (NAION) after taking drugs such as Ozempic, Wegovy and Mounjaro.

The lawsuits allege the companies failed to adequately warn patients about the potential risk, that is often irreversible.

What Is The Controversy?

US law firm Weitz & Luxenberg has filed more than 90 lawsuits in New Jersey state court since 2025 on behalf of people who say they developed NAION while taking Ozempic or Wegovy, according to The Wall Street Journal.

Separate federal lawsuits in Philadelphia accuse Novo Nordisk and Eli Lilly of failing to provide adequate warnings about the potential eye-related risk. The cases are pending.

Regulators in Europe and Australia have required warnings about a possible increased risk of NAION with some GLP-1 medicines after reviewing available evidence.

In the US, vision problems are listed as possible side effects, but the FDA does not currently require NAION to be listed as a specific risk. The FDA's Sentinel Initiative is reviewing the possible safety signal linking GLP-1 drugs to NAION.

"The FDA routinely monitors the safety of drug products post-marketing. The FDA identifies safety signals from a variety of sources, evaluates the available data and takes regulatory actions when appropriate,” an FDA spokesperson said, according to ABC News.

Also read: Ozempic, Wegovy, Mounjaro and Zepbound May Fuel Rare Brain Disorder, Study Finds

What Do The Drugmakers Say?

Novo Nordisk, which makes Ozempic and Wegovy, said it takes “all reports of adverse events very seriously” but called the personal injury lawsuits "without merit."

The company said it is "committed to patient safety and continuously monitors the safety profile of our GLP-1 RA products." It added that if "emerging safety data warrant further action, appropriate measures will be implemented".

Lilly, which makes Zepbound and Mounjaro, said patient safety is its "top priority."

"We actively monitor, evaluate, and report safety information for all our medicines to the FDA," the company said, adding that it continues to review data on potential ophthalmic issues.

What Does The Science Say?

The evidence linking GLP-1 drugs to NAION remains mixed. Some observational studies have found an association, while others have not. Researchers have not established that GLP-1 drugs cause NAION.

What Studies Have Found

• 2025 JAMA study: Among more than 159,000 people with type 2 diabetes, 35 GLP-1 users developed NAION versus 19 in the comparison group. Researchers also found an increased risk of other optic nerve disorders in 93 patients.
• Another 2025 JAMA study: Found no statistically significant association between GLP-1 use and NAION, although it reported a slight increase in diabetic retinopathy.
• 2026 safety analysis: A British Journal of Ophthalmology analysis of more than 30 million FDA adverse-event reports from 2017 to 2024 identified a safety signal linking semaglutide medicines to NAION.
• Wegovy vs Ozempic: The signal was nearly five times stronger for Wegovy than Ozempic, although both contain semaglutide.

The North American Neuro-Ophthalmology Society and American Academy of Ophthalmology said studies have produced mixed results.

"While many report a small possible increased risk of NAION in patients taking GLP-1 RAs such as semaglutide, some studies report no correlation, and the overall magnitude of the risk of NAION remains low,” the groups said.

Read More: Exclusive: GLP-1 Drugs Are The ‘New Statins’, Says University Hospital Birmingham Professor

What Is NAION?

NAION is the most common acute optic neuropathy in people over 50, according to Mayo Clinic. It occurs when blood flow to the optic nerve is suddenly reduced, damaging the nerve that carries visual information from the eye to the brain.

It typically causes painless vision loss in one eye.

Some patients experience partial improvement, but vision loss is often permanent. There is currently no proven treatment to reverse the damage.

Diabetes itself can increase the risk of NAION, regardless of GLP-1 use. Other risk factors include overnight low blood pressure and having a very small optic nerve cup.

The US Food and Drug Administration (FDA) has a step towards reducing animal use in drug research, focusing on technologies like human organoids, organs-on-chips, artificial intelligence and computer modelling that may play a bigger role in deciding whether medicines are safe before they are tested in people.

The move is part of the US Department of Health and Human Services's initiative declared on September 21 to shift biomedical research towards methods that reflect human biology more closely.

As part of the changes, the FDA issued a rule updating its regulations to state that non-animal methods can be used where it is appropriate to assess the safety of drugs before human trials.

“This new rule supports the Trump Administration’s push to explore ways to complement, or where appropriate, replace animal studies with methods that may better predict how medicines will actually affect people,” FDA Acting Commissioner Kyle Diamantas said.

“Our goal is not to replace one rigid approach with another. It is to support rigorous, modern science — including animal studies when they remain appropriate and validated alternatives when they can provide the evidence needed to protect patients,” he added.

Why Is FDA Moving Away From Animal-Based Studies?

Animal testing has always been a central part of drug development for decades. But a drug behaving safely in an animal does not necessarily mean it will behave the same way in humans. This is partly because species differ in their biology, metabolism and immune responses.

The FDA's new approach is built around New Approach Methodologies (NAMs), a term for covering laboratory and computational methods that can provide more accurate evidence without relying entirely on animals.

The agency has already issued guidance on how developers can use and validate these methods. It has also created a database containing examples of NAMs used in FDA reviews.

Also read: HHS Announces US FDA’s First AI Chief: Here’s What It Means For The Future Of Drug Regulation

Organoids May Replace Some Animal Experiments

Organoids are three-dimensional clusters of cells grown from human stem cells. They can replicate the structure and some of the function of organs.

Researchers can grow models resembling parts of the liver, intestine, brain, kidney or other tissues and use them to test experimental medicines. This can allow scientists to study how human cells respond directly to a drug, including side effects.

The HHS initiative includes plans for the NIH Clinical Center to develop a laboratory combining standardised human organoids with robotics, AI and advanced data systems.

Also read: Donald Trump Wants Childhood Vaccines Split Into 5 Shots To Prevent Autism: But Is There Evidence?

What Are Organs-On-Chips?

Organs-on-chips, also called microphysiological systems, are small devices containing human cells that mimic aspects of an organ's structure and environment. Researchers can expose these cells to drugs and observe their responses in a controlled environment.

For example, a liver-on-a-chip can help researchers investigate whether a drug damages liver cells, while other systems can model the interaction between different tissues.

The FDA says newer approaches include human cells, organs-on-chips and computer models, provided they are appropriately suitable scientifically.

Also read: Pennsylvania Measles Outbreak Crosses 700 Cases As State Seeks CDC Help

AI & Computational Models

AI and computational models can analyse huge amounts of biological and drug data to predict how a medicine may behave in the human body.

HHS' Advanced Research Projects Agency for Health is investing in computational approaches designed to assess drug safety and reduce dependence on animal experiments.

The FDA's rule, however, does not prohibit animal studies. Instead, it does away with language that imply animal testing is the only acceptable way to test drugs and biomedical products.

Non-animal studues can be used when they are scientifically appropriate for the particular drug and regulatory requirements.