The End of Insulin Injections? How Scientists Are Making Medicine Needle-Free

For decades, treating a life-threatening allergic reaction outside a hospital meant reaching for an epinephrine auto-injector. Now, some patients can reach for a nasal spray instead.

That new option, along with other injection-free medicines that have recently become available, could be especially consequential for people who fear needles. Nearly all young children and many teens and adults recoil at getting a shot—with some so paralyzed they avoid needed treatments and vaccines.

That hesitation can have serious health consequences. When a child has a severe allergic reaction, for example, some caregivers avoid emergency epinephrine auto-injectors because they fear hurting the child or the child is nervous about the prick. Delaying the medicine during anaphylaxis may cause serious symptoms to reappear hours later and lead to significantly longer ER stays.

But making a medicine needle-free is more complicated than simply repackaging an injectable drug. Some medicines have long been given as shots because they must enter the bloodstream quickly or would be destroyed during digestion. Now, technological advances are allowing certain drugs to be sprayed into the nose, inhaled into the lungs, or swallowed as pills. Each route presents a different challenge.

Needle-free options are currently available for certain forms of epinephrine, insulin, flu vaccine, and GLP-1 drugs, while ongoing research may yield even more ways to deliver medicine.

In one survey, fewer than half of American adults and children with food allergies said they always have an auto-injected epinephrine pen at hand, both because it’s bulky to carry and because they dislike the needle, says Thomas Casale, a pediatric and adult physician at the University of South Florida. Casale conducted studies of the intranasal spray and serves on the manufacturer’s scientific advisory board.

Even when a child is clearly struggling, “parents sometimes think, ‘Do I want to inject them with a needle?’” he says, a dilemma even more severe for other caregivers who aren’t trained to administer it.

To make the nasal spray possible, scientists had to overcome the tightly sealed membranes lining the nose, which slow the absorption of water-soluble molecules such as epinephrine.

Neffy was approved in 2024 for adults and children weighing at least 66 pounds. Its use has since expanded to anyone weighing at least 33 pounds. The epinephrine is combined with a chemical, n-dodecyl beta-D-maltoside, that temporarily loosens the nose’s tight junctions so the drug can reach the bloodstream quickly. The device, the size of a wireless earbud case, is much smaller than an auto-injector.

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Clinical studies show the nasal spray yields epinephrine levels comparable to the injected version. Subsequent research has found it effectively halts allergic reactions during food challenges in doctors’ offices in both the U.S. and in Japan.

Katelyn Wong, an allergist and immunologist at Yale Medicine, says a growing number of her allergy patients are turning to the newer device, although not all insurance currently covers it. “Many patients are interested because it is not a needle,” she says.

Reducing the number of shots is not the only advantage alternative delivery systems may offer. Inhaled insulin, for example, can start working faster than injected mealtime insulin. In May, the U.S. Food and Drug Administration approved inhaled insulin for children ages six and older with type 1 or insulin-requiring type 2 diabetes, following its authorization for adults 12 years earlier.

The speed is important because when a healthy person eats, say, a hot fudge sundae or a heaping plate of penne pasta, the body instantly starts regulating blood sugar. “Even before food hits your lips, you start to have reflexive increases in secretion of insulin. And as soon as the glucose starts to be absorbed, your pancreas rapidly increases the insulin secretion so that you maintain a glucose level that's the same value twenty-four/seven,” says Michael Haller, a pediatric endocrinologist at the University of Florida who led a large, randomized study finding that inhaled insulin works as well as injected insulin in kids. (He also serves on the manufacturer’s advisory board.)

People with type 1 diabetes make little or no insulin and must replace it with injections or an insulin pump. Every time they eat, they must calculate their carbohydrate intake and dose appropriately. But even when they are spot on, injected insulin doesn’t reach the bloodstream for 15 minutes, Haller says.

During the delay, or in cases where carb calculations are low, excessive glucose circulates, “adding to the person’s lifelong risk for complications with retinal disease, kidney disease, nerve damage, and heart damage,” he says.

Inhaled insulin is absorbed more rapidly through the lungs. The hormone is bound to carrier microparticles that deliver the powdered medicine deep inside the air sacs, which regularly interact with our blood. Its first measurable glucose-lowering effect occurs after about 12 minutes, and blood insulin concentrations peak within 10 to 20 minutes. The powder is delivered through a small handheld inhaler using cartridges containing four, eight, or 12 units, which can be combined for larger doses.

Although the adult version has been around for more than a decade, uptake for this group has been slow, likely because patients have been injecting insulin for many years and are hesitant to change, Haller says. Children newer to the disease are more likely to recoil at the frequent shots and, in fact, many of his pediatric patients are embracing the method and achieving tight insulin control. Most inhale the drug before eating, along with a single daily background insulin shot. Type 1 diabetes “is a terrible disease,” Haller says, “but telling them they can start with one injection a day and take a puff of insulin every time they eat, that’s a lot more palatable.”

Turning an injection into a pill presents a different problem. Many medicines are injected rather than given as a pill because stomach acids and digestive enzymes shred them before they reach the bloodstream. This is especially true for peptides, chains of amino acids that the digestive system treats much like food. But some manufacturers, including the maker of an oral GLP-1 drug, are finding ways to shield these medicines from digestion.

Oral semaglutide, approved for weight loss in 2025, combines the medicine with a pharmaceutical additive, salcaprozate sodium, or SNAC. As the tablet dissolves, SNAC temporarily raises the pH immediately around it, slowing digestive enzymes that would otherwise break down the drug. The additive also helps keep semaglutide molecules separate and temporarily makes the nearby stomach lining more permeable, allowing the medicine to pass into the bloodstream.

Even so, the body absorbs only about one to two percent of the semaglutide in the tablet. That is why the oral version is taken daily at a significantly higher dose, rather than weekly like the injection.

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Yet even when alternatives to shots exist, people don’t always use them. That’s been the case for the nasal flu vaccine, which was first approved in 2003. Fewer than 10 percent of vaccine doses are currently delivered this way (in part because the medicine is approved only for healthy, non-pregnant people ages 2 to 49, which leaves out high-risk groups and older people). Experts expect the number to increase now that the FDA allows people to take it at home, rather than only in a healthcare facility.

Other drug delivery methods may be on the horizon. Researchers are testing an epinephrine film placed under the tongue. The substance has been chemically modified to bind instantly to the tongue (preventing it from being swallowed) and to dilate blood vessels in the mouth to speed absorption. Preliminary studies show promising results.

Jet injectors could be especially useful for vaccination campaigns. These devices force a high-pressure stream of immunization the width of a human hair through the skin in a fraction of a second. The method produces similar immunological responses as shots, researchers noted in a review published in March in the journal Pharmaceutics. Jet injectors could speed mass-vaccination campaigns, eliminate needle waste, and, in some cases, require less vaccine per patient, the reviewers noted. During its emergency COVID-19 campaign, India utilized one such injector.

Needle-free does not mean sensation-free. A jet injection feels like a snapping rubber band, for example, while nasal sprays can irritate the throat. Nor will these methods replace shots for every drug or every patient. But for anyone who gets weak-kneed at the sight of a needle, the growing array of alternatives could make the difference between delaying treatment and receiving it promptly.