Amylin analogues as monotherapy and in combination
What is the effect of an amylin receptor agonist alone and in combination with a glucagon-like peptide-1 receptor agonist on body weight?
§1Abstract
§1.1Review question
What is the effect of an amylin receptor agonist alone and in combination with a glucagon-like peptide-1 receptor agonist on body weight?
§1.2PICO frame
Table 1. The registered PICO frame. Any change made after protocol registration is recorded in the amendment log at §5 and is identified there as post hoc.
| Element | As registered |
|---|---|
| Population | Adults with obesity, with and without type 2 diabetes. |
| Intervention | Cagrilintide, petrelintide or pramlintide alone or in fixed combination. |
| Comparator | Placebo or the glucagon-like peptide-1 receptor agonist component alone. |
| Outcomes | Percentage change in body weight; nausea; injection-site reactions. |
§1.3Method in brief
A review of the effects of an intervention on pre-specified outcomes, with a quantitative synthesis where the contributing studies are sufficiently similar. The protocol was registered with the Institute's secretariat before the search was executed. The search was run on 10 June 2026 across 8 sources and is reproduced in full at §2. Screening, extraction and certainty assessment were performed independently by two members of the secretariat with disagreement resolved by a third.
§1.4Conclusion
Moderate certainty evidence indicates that a long-acting amylin analogue produces a weight reduction of roughly 8 to 11 % as monotherapy and that the fixed combination with semaglutide exceeds either component alone. Whether the combination effect exceeds what the same total incretin exposure would achieve is not established by any contributing trial, because no trial randomised participants to a dose-matched comparison of that kind. The Institute records the confirmatory combination result as smaller than the phase 2 estimate had implied.
The conclusion rests on 8 contributing studies, listed with their extracted data at §3 and summarised outcome by outcome at §4.
§1.5Limitations
§1.6Consultation
This review was released for public comment before ratification. Draft synthesis: Amylin analogues as monotherapy and in combination received 9 submissions. Amendments arising are recorded in the amendment log and are traceable to a numbered submission.