Obesity and overweight in adults — compounds assessed
The 23 compounds the Institute assesses in obesity and overweight in adults.
§4Compounds assessed
Compounds the Institute assesses in this indication, with the class of each and its overall certainty. A compound appears here whether or not the evidence supports its use, because recording that a compound has been studied and found wanting is as much part of the assessment as recording that one has not.
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−8.0 % body weight at 56 weeks with 3.0 mg versus −2.6 % with placebo — Consistent across the SCALE programme. Inferior to semaglutide 2.4 mg in a direct comparison (STEP 8).
High -
−14.9 % body weight at 68 weeks with semaglutide 2.4 mg versus −2.4 % with placebo — Consistent across five phase 3 trials with a common titration schedule and a common primary analysis timepoint. Effect is attenuated but preserved in the presence of type 2…
High -
−20.9 % body weight at 72 weeks with 15 mg versus −3.1 % with placebo (SURMOUNT-1) — The largest placebo-subtracted weight effect of any approved agent at the date of this cycle. SURMOUNT-5 reported superiority over semaglutide 2.4 mg (−20.2 % versus −13.7 %).
High -
A 12-week phase 2b trial in 300 participants did not demonstrate a statistically significant difference in body weight versus placebo at any dose — The Institute rates the *negative* finding as moderate certainty — this is a real randomised trial with a clear…
Moderate -
−10.8 % body weight at 26 weeks with cagrilintide 4.5 mg monotherapy versus −3.0 % with placebo, and −8.6 % with liraglutide 3.0 mg as active reference — Phase 2 dose-finding, 706 participants. Monotherapy effect is smaller than that of the incretin class…
Moderate -
Fixed-ratio combination of a long-acting amylin analogue and a GLP-1 receptor agonist3 contributing trialsfull monograph
−22.7 % body weight at 68 weeks versus −2.3 % with placebo in adults with obesity without diabetes — Large phase 3 trial. Downgraded one level because the observed effect fell below the sponsor-stated expectation and because a substantial proportion of…
Moderate -
−4.6 kg at 4.5 mg over 52 weeks in type 2 diabetes — No dedicated obesity programme; weight effect is modest relative to the acylated analogues.
Moderate -
GLP-1 receptor agonist (exendin-based, short- and extended-release)1 contributing trialfull monograph
−2.3 to −3.6 kg — No obesity indication was pursued.
Moderate -
−1.8 to −2.7 kg — No obesity programme.
Moderate -
Dual glucagon and GLP-1 receptor agonist (oxyntomodulin analogue)3 contributing trialsfull monograph
−14.4 % body weight at 48 weeks with 6 mg in a Chinese phase 3 trial versus −0.3 % with placebo — Phase 3 conducted predominantly in a Chinese population. Downgraded one level for indirectness when applied to other populations, since baseline body weight and…
Moderate -
−14.7 % body weight at 36 weeks with 45 mg in the phase 2 trial versus −2.3 % with placebo — Phase 2 at 36 weeks with weight still declining at the final timepoint, so the plateau effect is unknown. Downgraded for indirectness of duration.
Moderate -
−24.2 % body weight at 48 weeks with 12 mg in the phase 2 trial versus −2.1 % with placebo — The largest weight effect reported for any single agent, but from a phase 2 trial of 338 participants. Downgraded from high for indirectness of dose and imprecision…
Moderate -
−15.1 % body weight with oral 50 mg at 68 weeks versus −2.4 % with placebo — The 50 mg obesity dose is a different formulation strength from the diabetes product; certainty is downgraded one level for single-trial evidence at that dose.
Moderate -
−14.9 % body weight at 46 weeks with 6.0 mg in phase 2 versus −2.8 % with placebo — Phase 2 dose-finding, 387 participants; phase 3 unreported at this cycle.
Moderate -
−13.1 % body weight at 12 weeks in a phase 1b subcutaneous study versus −1.1 % with placebo — A 12-week phase 1b result. The Institute reports the figure because it is the only human efficacy datum available, and states plainly that a 12-week weight…
Low -
−8.0 to −13.0 % body weight at 32 weeks across doses, with discontinuation rates above 50 % in some arms — Downgraded two levels: attrition above 50 % in the higher-dose arms makes the treatment-policy estimate unreliable.
Low -
−13.2 % body weight at 48 weeks with the highest dose versus −0.5 % with placebo in a Chinese phase 3 trial — Downgraded for geographic indirectness and because the Institute could not verify the primary publication against an independent record at this cycle.
Low -
GIP receptor antagonist and GLP-1 receptor agonist conjugate (antibody–peptide)2 contributing trialsfull monograph
−16.2 % body weight at 52 weeks at the highest dose in phase 2 versus −2.5 % with placebo — Phase 2 with a modest sample and high gastrointestinal event rates on initiation. Downgraded for imprecision and for single-trial evidence.
Low -
−8.6 % body weight at 16 weeks in a phase 1b multiple-ascending-dose study versus −1.7 % with placebo — Phase 1b with a 16-week horizon. The gastrointestinal adverse-event incidence was lower than that reported for incretin analogues at comparable weight…
Low -
−3.7 kg at 16 weeks versus placebo in a non-diabetic obesity study — No obesity indication was pursued; the compound requires three-times-daily injection.
Low -
No human trial of any kind identified — Rodent diet-induced obesity models only. The Institute found no registered clinical trial of this compound.
Very low -
Non-selective melanocortin receptor agonist (cyclic heptapeptide)0 contributing trialsfull monograph
No randomised trial identified — Appetite suppression is reported anecdotally and is mechanistically expected from MC4R agonism, but no trial exists.
Very low -
No randomised controlled human trial identified — Rodent diet-induced obesity models only.
Very low
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, Lau DCW, le Roux CW, Violante Ortiz R, Jensen CB, Wilding JPH. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. New England Journal of Medicine 2015;373(1):11–22. doi:10.1056/NEJMoa1411892 · PMID 26132939
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.