How do the next wave of weight-loss drugs differ from current GLP-1 treatments?

Amylin is a hormone released after eating. Medicines that act on its receptor use a pathway distinct from GLP-1 and GIP, potentially adding another signal involved in fullness. Whether that difference gives patients a meaningful advantage depends on the results of clinical trials, not the number of pathways a drug targets.

Novo Nordisk’s CagriSema pairs semaglutide with cagrilintide, an amylin analogue. Eli Lilly’s EloraTZP pairs tirzepatide with eloralintide, which acts on the amylin receptor. Zealand Pharma and Roche are developing petrelintide, an amylin analogue tested on its own rather than alongside a GLP-1 drug.

Lilly’s retatrutide takes a different approach: it targets GLP-1, GIP and glucagon receptors. It is not an amylin combination. That distinction matters because results for one approach cannot be assumed to apply to the others, even when they are discussed together as the next generation of weight-loss medicines.

What do the weight-loss trials actually show?

For CagriSema, Novo reported that participants lost 22.4% of their starting body weight after 52 weeks in a placebo-controlled study, as TIME reported. The result is substantial, but it does not show how CagriSema would perform against every current or experimental treatment.

In a Phase 2b study of 367 people with overweight or obesity and Type 2 diabetes, Lilly said participants receiving the highest-dose EloraTZP combination lost 23.3% of their body weight after 48 weeks. Those receiving tirzepatide 15 mg lost 14.8%. The company also reported larger reductions in A1C, a measure of blood-sugar control, with the highest-dose combination than with tirzepatide alone in that study.

Petrelintide was tested in people with overweight or obesity who did not have diabetes. Average weight loss was 10%, compared with 1.7% with placebo, according to a report on the Phase 2 findings. Its result answers a different question from the EloraTZP trial: what happened when an amylin-based medicine was tested without a GLP-1 drug in a different population.

In a retatrutide study involving people with Type 2 diabetes, those receiving the highest dose lost about 18.8% of body weight over roughly a year and a half, compared with 5.1% for placebo recipients, TIME reported. About one-third of the highest-dose group lost at least 25% of their body weight, compared with 3% of the placebo group. A separate study of people without diabetes reported about 25% weight loss at the highest dose.

These figures are not a leaderboard. The trials enrolled different people, ran for different lengths of time and used different comparison groups. EloraTZP was tested against an active treatment, tirzepatide; other results cited here were compared with placebo. Direct comparisons and further studies are needed before patients and clinicians can judge which option offers the best balance of benefits and risks.

What do the studies say about side effects and other health benefits?

Weight loss is only part of a treatment decision. TIME reports that about 40% of people who start current GLP-1 medicines stop within a year, although that figure does not establish why each person stopped or how the rate varies by drug. A new medicine’s value will depend in part on whether people can tolerate and continue it.

Amylin-based treatments are not free of side effects. In the petrelintide study, nausea was reported by 20% of recipients and 6% of people given placebo. Dr. Timothy Garvey, who led that trial, told TIME, “As more of these tools become available, we can individualize care better.” That is a possibility for future care, not proof that every amylin-based drug will be easier to take.

Adding amylin activity may also bring trade-offs. In Lilly’s EloraTZP trial, discontinuation because of adverse events ranged from 10.8% to 27.0% across the combination groups, higher than in the tirzepatide-only group, according to Lilly’s results. Those are trial discontinuations due to adverse events; they are not directly comparable with TIME’s estimate of how many people stop existing GLP-1 medicines within a year.

Other reported findings may matter to patients, but they require the same care in interpretation. Participants with knee osteoarthritis in a retatrutide study reported lower pain scores than placebo recipients, and participants with obstructive sleep apnea reported fewer apnea episodes. Those findings do not mean retatrutide is approved for either condition or that every patient would experience those benefits. It also remains unclear how long weight loss and other effects persist with the experimental medicines, including after treatment stops.

When might patients get these medicines, and what would they cost?

CagriSema is the furthest along in the U.S. regulatory process among these candidates. Novo Nordisk says it filed an application for weight management in December 2025 and expects a Food and Drug Administration decision in the fourth quarter of 2026. The medicine remains investigational; an expected decision is not an approval.

The others remain in testing. Lilly says it plans to begin Phase 3 studies of EloraTZP by the end of 2026. Its stated plan, reported by TIME, is to submit retatrutide for FDA approval in early 2027. Petrelintide’s reported results come from a Phase 2 trial. Plans for further testing and applications can change, and none establishes when a medicine might become available.

The companies have a commercial interest in how these results are received. Novo develops CagriSema; Lilly develops EloraTZP and retatrutide; Zealand Pharma and Roche are developing petrelintide. Company-reported findings are useful evidence about specific trials, but they cannot replace larger follow-up studies or direct comparisons among treatments.

Patients also cannot choose a medicine they cannot obtain. The reported efficacy results establish no future price, insurance coverage or level of availability for these candidates. Alongside the FDA’s pending CagriSema decision, those unanswered access questions will determine whether promising trial results become a practical treatment option.