Evidence synthesis · §3
Counter-ion content and its effect on delivered peptide mass — included and excluded studies
The included-studies table with extracted data, the exclusions with reasons, and the risk-of-bias judgements.
§3Included and excluded studies
Every study contributing to this review is listed below with the data extracted from it. The extraction table is published at the level of the individual outcome and study so that the synthesis can be checked without the reader having to retrieve each source.
§3.1Included studies
Table 4. Included studies with the characteristics extracted from each.
| Study | Design | Randomised | Duration | Anchor outcome as reported | Year |
|---|---|---|---|---|---|
| ACHIEVE-1Orforglipron | Randomised, double-blind, placebo-controlled | — | 40 weeks | no result held | 2025 |
| ACHIEVE-2Orforglipron | Randomised, double-blind, active-controlled | — | 52 weeks | no result held | 2025 |
| ATTAIN-1Orforglipron | Randomised, double-blind, placebo-controlled | — | 72 weeks | The Institute holds a headline result indicating a weight effect intermediate between the injectable single agonists and placebo, and awaits the full… | 2025 |
| ATTAIN-2Orforglipron | Randomised, double-blind, placebo-controlled | — | 72 weeks | no result held | 2025 |
| ECNO-PH3-CN-OBESITYEcnoglutide | Randomised, double-blind, placebo-controlled | 664 | 48 weeks | Mean change −13.2 % at 2.4 mg versus −0.5 % with placebo | 2025 |
| ECNO-PH3-CN-T2DEcnoglutide | Randomised, double-blind, placebo-controlled | — | 52 weeks | no result held | 2025 |
| ESSENCESemaglutide | Randomised, double-blind, placebo-controlled | 1,197 | 72 weeks for part 1 | Resolution in 62.9 % versus 34.3 % with placebo; difference 28.7 percentage points (95 % CI 21.1 to 36.2) | 2025 |
| EXENATIDE-GE-PDExenatide | Randomised, double-blind, placebo-controlled | 194 | 96 weeks | No significant difference from placebo. The Institute records this as a negative result of a widely publicised earlier phase 2 signal | 2025 |
| GLORY-1Mazdutide | Randomised, double-blind, placebo-controlled | 610 | 48 weeks | Mean change −14.0 % at 6 mg versus +0.3 % with placebo | 2025 |
| REDEFINE-1CagriSema (cagrilintide with semaglutide) | Randomised, double-blind, placebo-controlled | 3,417 | 68 weeks | Mean change −22.7 % versus −2.3 % with placebo | 2025 |
| REDEFINE-2CagriSema (cagrilintide with semaglutide) | Randomised, double-blind, placebo-controlled | 1,206 | 68 weeks | Mean change −15.7 % versus −3.1 % with placebo | 2025 |
| SOULSemaglutide, oral | Event-driven cardiovascular outcome trial | 9,650 | Median 47.5 months | Hazard ratio 0.86 (95 % CI 0.77 to 0.96) | 2025 |
| STRIDESemaglutide | Randomised, double-blind, placebo-controlled | 792 | 52 weeks | Estimated treatment ratio 1.13 (95 % CI 1.06 to 1.21) | 2025 |
| SURMOUNT-5Tirzepatide | Randomised, open-label, active-controlled | 751 | 72 weeks | Mean change −20.2 % with tirzepatide versus −13.7 % with semaglutide | 2025 |
| SURMOUNT-KOATirzepatide | Randomised, double-blind, placebo-controlled | — | 68 weeks | Improvement relative to placebo. The Institute records that pain improvement in a weight-loss trial cannot be attributed to a direct joint effect | 2025 |
| SURPASS-CVOTTirzepatide | Event-driven cardiovascular outcome trial | 13,299 | Median 4.5 years | Non-inferior to dulaglutide on the primary composite. The Institute records that an active-controlled non-inferiority design cannot establish superiority over… | 2025 |
| DREAMS-1Mazdutide | Randomised, double-blind, placebo-controlled | 319 | 24 weeks | A reduction of approximately 1.6 percentage points at 6 mg versus 0.1 with placebo | 2024 |
| DREAMS-2Mazdutide | Randomised, double-blind, placebo-controlled | 731 | 48 weeks | A dose-dependent glycaemic effect with concurrent weight reduction | 2024 |
| FLOWSemaglutide | Event-driven kidney outcome trial | 3,533 | Median 3.4 years | Hazard ratio 0.76 (95 % CI 0.66 to 0.88); annual eGFR slope difference 1.16 mL/min/1.73 m² per year | 2024 |
| MARITIDE-PH2-OBESITYMaridebart cafraglutide | Randomised, double-blind, placebo-controlled | 592 | 52 weeks | Mean change of approximately −20 % at the highest dose without a weight plateau at 52 weeks | 2024 |
| MARITIDE-PH2-T2DMaridebart cafraglutide | Randomised, double-blind, placebo-controlled | — | 52 weeks | A smaller weight effect than in participants without diabetes, consistent with the rest of this class | 2024 |
| PETRE-PH1BPetrelintide | Phase 1 ascending dose | — | 16 weeks | Weight reduction of approximately 8.6 % at 16 weeks in a phase 1b setting | 2024 |
| REIMAGINE-1Amycretin | Phase 1 ascending dose | 125 | Up to 36 weeks | Exploratory weight reduction of approximately 13 % at 12 weeks with the subcutaneous presentation. The Institute treats an exploratory endpoint in a phase 1… | 2024 |
| STEP-HFpEF-DMSemaglutide | Randomised, double-blind, placebo-controlled | 616 | 52 weeks | Directionally consistent with STEP-HFpEF with a smaller weight effect, as expected in a population with diabetes | 2024 |
| 24 included studies. Each links to its structured abstract, which carries a field-by-field provenance table distinguishing extracted figures from Institute reconstructions. | |||||
Contributing participants across studies reporting a randomised total: 37,696. Studies for which the Institute does not hold a randomised total contribute to the qualitative synthesis and not to any pooled figure.
§3.2Excluded at full text, with reasons
Table 5. Reports excluded at full text, by reason. A review that reports an exclusion count without reasons cannot be checked against its own protocol.
| Reason for exclusion | Reports |
|---|---|
| Not a randomised comparison | 9 |
| Population outside the review question | 8 |
| Intervention outside the review question | 6 |
| Comparator not eligible | 7 |
| No eligible outcome reported | 3 |
| Duplicate report of an included study | 4 |
| Conference abstract without extractable data | 11 |
| Retracted or subject to an expression of concern | 12 |
| 45 reports excluded at full text in total. | |
§3.3Risk of bias across included studies
Table 6. Risk-of-bias judgement recorded for each included study on the review's anchor outcome.
| Study | Risk of bias | Inconsistency | Indirectness | Imprecision | Publication bias |
|---|---|---|---|---|---|
| ACHIEVE-1 | Some | Low | Low | Low | Some |
| ACHIEVE-2 | Some | Low | Low | Some | Low |
| ATTAIN-1 | Some | Low | Low | Low | Low |
| ATTAIN-2 | Low | Low | High | Low | Low |
| ECNO-PH3-CN-OBESITY | Low | Low | Some | Some | Low |
| ECNO-PH3-CN-T2D | Some | Low | Low | Low | Some |
| ESSENCE | Low | Low | Some | Low | Low |
| EXENATIDE-GE-PD | Low | Low | Some | Low | Low |
| GLORY-1 | Some | Low | Low | Low | Low |
| REDEFINE-1 | Low | Low | Low | Some | Low |
| REDEFINE-2 | Low | Low | Low | Some | Low |
| SOUL | Low | Low | Low | Low | Some |
| STRIDE | Low | Low | Low | Some | Low |
| SURMOUNT-5 | Low | Low | Low | Low | Low |
| Judgements are the Institute's own and are recorded per outcome. A study may carry a different judgement in a different review that assesses a different outcome from it. | |||||
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.
- United States Pharmacopeial Convention. General Chapter ⟨1225⟩ Validation of Compendial Procedures. United States Pharmacopeia — National Formulary (USP–NF) 2024;USP 2024 Issue 1. identifier not held by the Institute
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.
Compound Evidence Institute · CEI-ES-013/3 · https://compoundevidence.com/syntheses/counterion-content-underreporting/included-studies/ · retrieved 30 July 2026