For millions of people taking weight loss drugs, the next breakthrough may not be more weight loss. It may be fewer injections.

Pfizer and Amgen are developing monthly GLP-1 shots — a departure from injections like Wegovy and Zepbound, which are taken weekly.

The goal, the drugmakers say, is to make weight loss drugs more convenient and easier to stick with.

“Whether it’s a daily pill, a weekly injection or even a monthly injection, the more frequently a medication must be taken, the more opportunities there are to miss doses or stop treatment altogether,” said Dr. Christopher McGowan, a gastroenterologist who runs a weight loss clinic in Cary, North Carolina.

Dr. John Buse, an endocrinologist at the University of North Carolina School of Medicine, said patients “really like the idea” of a monthly GLP-1 shot.

“The straight-up benefit of the once-monthly dose is you get 12 injections a year versus 52 a year,” said Buse, who worked on the trial of Pfizer’s monthly shot.

All GLP-1 drugs start with the same premise: They’re molecules that bind to the GLP-1 receptor, setting off a cascade of signals in the body that regulate blood sugar and feelings of hunger. That’s how semaglutide, the ingredient in Ozempic and Wegovy, works. But drugmakers soon began expanding what GLP-1s could do. Tirzepatide, the ingredient in Mounjaro and Zepbound, binds to a second receptor, called GIP. Eli Lilly’s experimental drug, retatrutide, adds in a third.

In all of these cases, the body begins to break down the active ingredients after about seven days, so weekly doses are needed to maintain the effects. To make monthly dosing possible, Pfizer and Amgen had to engineer new drugs that remain active in the body far longer.

Pfizer’s experimental drug berobenatide works by staying attached longer to a protein in the blood called albumin, which protects the molecule from being broken down too quickly.

Pfizer presented results from the first 28 weeks of its ongoing middle-stage trial on the drug at the American Diabetes Association’s annual conference on Saturday.

It found the drug helped patients lose up to 12.3 % of their body weight, on average. Data from another midstage trial also presented Saturday, in patients with Type 2 diabetes, found that berobenatide helped patients manage their blood sugar levels.

To help manage side effects, participants in the weight loss trial began with lower doses that were gradually increased over the first few weeks. They also started on weekly injections for 12 weeks before moving to monthly shots. The trial is set to run for 64 weeks.

Buse said side effects from the drug — mainly gastrointestinal symptoms — were similar to or not as bad as those seen with other GLP-1 drugs. Issues were more common when patients first transitioned from weekly to monthly dosing, he said.

Buse said the drug binds to the GLP-1 receptor in a way that minimizes the side effects.

“The GLP-1 receptor where the GLP-1 docks, it has got two signaling paths that it works through. And this one [berobenatide] is driving one of those two, whereas normally when you have a GLP-1 molecule, it drives both at the same time,” he said.

Amgen’s monthly GLP-1 uses an antibody to prolong its stay in the body. The drug, called MariTide, is currently being tested in late-stage trials.

Murielle Veniant-Ellison, who heads Amgen’s obesity research and development, said that in addition to the drug binding to the GLP-1 receptor, its antibody also targets the GIP receptor, like tirzepatide. Unlike tirzepatide, however, Amgen’s drug blocks this receptor.

Scientists still don’t fully understand why both activating and blocking GIP can result in weight loss, said Dr. Daniela Hurtado Andrade, an endocrinologist at the Mayo Clinic in Jacksonville, Florida. “I don’t think there is a definite answer yet.”

Results from a midstage trial of nearly 600 adults published last year found MariTide helped patients lose up to 20% of their body weight, on average, after 52 weeks. Side effects were similar to those for other GLP-1 medications, mainly gastrointestinal problems.

Veniant-Ellison said patients in the trial could have lost even more weight. “It’s only 52 weeks, so it’s not a long-term effect,” she said.

Amgen is testing whether MariTide could be taken even less frequently — every other month or every three months — as well as whether it can treat obesity-related problems such as heart disease and sleep apnea.

Dr. Susan Spratt, an endocrinologist and the senior medical director for the Population Health Management Office at Duke Health in North Carolina, said a monthly GLP-1 drug could be good for patients who struggle with sticking to the dosing schedule or who just prefer taking medication less often. (Spratt owns stock in Amgen.)

Taking medication less frequently, however, isn’t always “better and easier,” she said. “Sometimes people need a routine and monthly might not be routine enough.”

Spratt said she would likely prefer to start a patient on a weekly injection first, and then transition them to a monthly injection if they tolerate the side effects well and successfully stick with the routine.

Hurtado Andrade, of Mayo, said a monthly injection could appeal even to people who rarely miss a weekly dose because unexpected life events can still get in the way.

Taylor McDaniels, 25, of Pittsburgh, said she’s generally diligent about taking her weekly injection.

Still, McDaniels said, there have been times when she’s struggled to keep up with the weekly schedule, whether because she was traveling and forgot her shot or because she was feeling sick.

“I haven’t been perfect,” said McDaniels, who takes compounded tirzepatide. “Sometimes life happens.”

She added that she’d still have questions about a monthly option, including potential side effects and whether it reduces food noise as effectively — and for as long — as the existing drugs.