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What’s next for GLP-1s?

Drugmakers that have raked in billions from GLP-1s, such as Ozempic maker Novo Nordisk, are racing to figure out how to innovate as sales of the blockbuster drug start to slow. The next big thing in the GLP-1 space will likely be more user-friendly versions of the drugs: oral pills, rather than the injectable formats popular weight loss drugs typically come in, Jayne Hornung, chief clinical officer at pharma consultancy MMIT, told Healthcare Brew. “Patients always prefer an oral tablet over having to self-inject something, so I see this becoming the market leader in GLP-1s,” Hornung said.

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 GLP-1 pills for weight loss: The race is on

As more oral GLP-1 agonists enter the market, they are predicted to capture over one-third of the GLP-1 weight management market. Although individual trials do not show that tablets are superior to injections for promoting weight loss, some patients may gravitate toward oral GLP-1s simply because of their ease of use and storage. This may be especially true given the similarities in side effect profiles.

 Oral GLP-1s Beyond the Hype: The Polypharmacy Challenge

Oral GLP-1 receptor agonists are generating a great deal of excitement as a potential inflection point in diabetes and obesity care. Amid the enthusiasm, however, a quieter and clinically important issue is emerging for primary care clinicians: how oral GLP-1s interact with the realities of polypharmacy and medication timing in everyday practice. Unlike injectable GLP-1s, oral formulations depend on precise dosing conditions and alter gastric physiology, raising questions about drug-drug interactions, inconsistent exposure, and silent erosion of therapeutic benefit in real-world use.

Articles of Interest

Cheaper, highly effective oral 'Ozempic' drugs are on the way

The one-a-day glucagon-like peptide-1 receptor (GLP-1R) agonist tablet would work much like the current suite of medications including Wegovy and Ozempic, (semaglutide) and Zepbound (tirzepatide), but would take away the need to self-inject the drug in order to achieve the same weight-loss results. These small-molecule drugs effectively target the gastrointestinal tract, doing away with the need to administer the medication by injection.

Eli Lilly’s Weight-Loss Pill Sheds Pounds Fast—But Hits a Plateau: What New Trial Results Mean for the Obesity Drug Race

The appeal of a pill form is enormous. Weight-loss jabs have been game-changers, but a daily tablet is seen as a next-gen solution because it would be easier and more convenient for patients and healthcare systems alike theguardian.com. No needles, syringes, or special refrigeration required – just a swallow of a pill. Tablets are also expected to be cheaper to produce and distribute. “Pill versions are seen as a holy grail because they are easier to store, distribute and administer and are also expected to be cheaper,” The Guardian noted in its coverage theguardian.com. In short, an effective pill could make advanced obesity treatment far more accessible to millions who need it.

GLP-1 pills are coming, and they could revolutionize weight-loss treatment

It’s a field that’s already undergoing a revolution, with millions of people across the US now using semaglutide and tirzepatide, sold as Wegovy and Zepbound for weight loss (and for diabetes as the better-known Ozempic and Mounjaro). Dushay cited hopes that pill versions of GLP-1 drugs could ease shortages, come at lower cost and enhance convenience. But she and other doctors also warn about the potential for misuse, a problem that could become more pervasive with daily pills instead of weekly injections; they could make it easier to take more than recommended or to share medication inappropriately.

Hate needles? Lilly’s weight-loss pill could get FDA approval next year, CEO says

The experimental pill for chronic weight management is called orforglipron—Ricks joked that even he had to practice pronouncing it—and designed to be taken once a day. By comparison, Zepbound is injected once a week. And whereas Zepbound is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist medication, orforglipron is classified as a nonpeptide GLP-1 receptor agonist drug.

Is the first GLP–1 pill around the corner?

Trial results of a daily oral GLP–1, orforglipron, show a clinically significant reduction of glucose levels and weight among patients with early diabetes. Orforglipron also reportedly has a simpler production process than injected GLP-1 drugs such as Ozempic and tirzepatide (sold as Mounjaro) and does not require cold storage – factors that could help improve access to the drug if it is approved for use.

Lilly’s GLP-1 pill outperforms Novo’s oral treatment in diabetes study

An investigational GLP-1 pill from Eli Lilly helped diabetes patients lower their blood sugar and weight more than an oral version of Ozempic sold by Novo Nordisk, results that support the efficacy of Lilly’s medicine as the company prepares to submit it to regulators. In a yearlong Phase 3 trial, the highest dose of Lily’s pill, orforglipron, lowered a measure of blood sugar called A1C by 1.9 percentage points, while the highest dose of Novo’s drug, marketed as Rybelsus, lowered A1C by 1.5 percentage points, when analyzing all patients regardless of discontinuations. The highest doses of Lilly’s and Novo’s pills also led to 8.2% and 5.3% weight loss, respectively.

Oral GLP-1 Agonist Orforglipron Shows Promise for Type 2 Diabetes and Weight Management

Orforglipron is a nonpeptide GLP-1 receptor agonist that functions by stimulating insulin release from the pancreas and slowing gastric emptying, which can promote satiety, reduce food intake, and lead to weight loss. Its unique small-molecule structure distinguishes it from other GLP-1 drugs, potentially facilitating easier absorption within the body. Additionally, orforglipron could be less expensive than currently available injectable GLP-1 drugs like semaglutide (Ozempic; Novo Nordisk) or dulaglutide (Trulicity; Eli Lilly and Company), making it more accessible to patients.

Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes

Orforglipron is a small-molecule, nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist in clinical development for type 2 diabetes and weight management. Additional data on the efficacy and safety of orforglipron are needed.

The Race for the Next Ozempic

The next wave of obesity drugs could help people lose even more weight—and make some pharma companies a fortune.

These Powerful Weight Loss Drugs Are Transforming Obesity Treatment – But Not Without Risks

With various drugs now in development, the idea of popping a pill to shed fat could very soon become a reality. But as these medicines become cheaper and more accessible, crucial questions arise. Are we truly on the brink of a cure for obesity? Or could neglecting the root causes risk worsening the very problems we seek to solve?