Evidence synthesis · §3
The rodent thyroid C-cell signal and its human relevance — 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 |
|---|---|---|---|---|---|
| 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 |
| STRIDESemaglutide | Randomised, double-blind, placebo-controlled | 792 | 52 weeks | Estimated treatment ratio 1.13 (95 % CI 1.06 to 1.21) | 2025 |
| 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 |
| 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 |
| SELECTSemaglutide | Event-driven cardiovascular outcome trial | 17,604 | Mean 39.8 months | Hazard ratio 0.80 (95 % CI 0.72 to 0.90); 6.5 % versus 8.0 % | 2023 |
| STEP-HFpEFSemaglutide | Randomised, double-blind, placebo-controlled | 529 | 52 weeks | Clinical summary score improved 16.6 points versus 8.7 points with placebo; estimated difference 7.8 points (95 % CI 4.8 to 10.9) | 2023 |
| STEP-5Semaglutide | Randomised, double-blind, placebo-controlled | 304 | 104 weeks | Mean change −15.2 % versus −2.6 % with placebo; the longest randomised exposure in the programme | 2022 |
| STEP-8Semaglutide | Randomised, double-blind, active-controlled | 338 | 68 weeks | Mean change −15.8 % with semaglutide versus −6.4 % with liraglutide; difference −9.4 percentage points (95 % CI −12.0 to −6.8) | 2022 |
| STEP-TEENSSemaglutide | Randomised, double-blind, placebo-controlled | 201 | 68 weeks | Mean change −16.1 % versus +0.6 % with placebo; estimated difference −16.7 percentage points (95 % CI −20.3 to −13.2) | 2022 |
| AMPLITUDE-OExenatide | Event-driven cardiovascular outcome trial | 4,076 | Median 1.8 years | Hazard ratio 0.73 (95 % CI 0.58 to 0.92), with a composite kidney outcome also reduced | 2021 |
| STEP-1Semaglutide | Randomised, double-blind, placebo-controlled | 1,961 | 68 weeks | Mean change −14.9 % with semaglutide 2.4 mg versus −2.4 % with placebo; treatment difference −12.4 percentage points (95 % CI −13.4 to −11.5) | 2021 |
| STEP-2Semaglutide | Randomised, double-blind, placebo-controlled | 1,210 | 68 weeks | Mean change −9.6 % with semaglutide 2.4 mg versus −3.4 % with placebo; the effect is attenuated relative to STEP 1, which the Institute records as a consistent… | 2021 |
| STEP-3Semaglutide | Randomised, double-blind, placebo-controlled | 611 | 68 weeks | Mean change −16.0 % with semaglutide 2.4 mg versus −5.7 % with placebo | 2021 |
| STEP-4Semaglutide | Randomised withdrawal | 803 | 48 weeks after a 20-week run-in | Continued treatment −7.9 % versus +6.9 % after switching to placebo; the Institute reads this as evidence that the effect is maintained by continued exposure… | 2021 |
| AWARD-11Dulaglutide | Randomised, double-blind, active-controlled | 1,842 | 36 weeks | Dose-dependent additional glycaemic and weight effect at 3.0 mg and 4.5 mg | 2020 |
| SCALE-TEENSLiraglutide | Randomised, double-blind, placebo-controlled | 251 | 56 weeks | Estimated difference in body-mass index standard-deviation score of −0.22 versus placebo | 2020 |
| REWINDDulaglutide | Event-driven cardiovascular outcome trial | 9,901 | Median 5.4 years | Hazard ratio 0.88 (95 % CI 0.79 to 0.99) | 2019 |
| AWARD-7Dulaglutide | Randomised, open-label, active-controlled | 576 | 52 weeks | Non-inferior glycaemic control with a smaller decline in eGFR than insulin glargine | 2018 |
| HARMONY-OUTCOMESDulaglutide | Event-driven cardiovascular outcome trial | 9,463 | Median 1.6 years | Hazard ratio 0.78 (95 % CI 0.68 to 0.90) | 2018 |
| SUSTAIN-7Semaglutide | Randomised, double-blind, active-controlled | 1,201 | 40 weeks | Difference −0.41 percentage points (95 % CI −0.57 to −0.25) for semaglutide 1.0 mg versus dulaglutide 1.5 mg | 2018 |
| EXSCELExenatide | Event-driven cardiovascular outcome trial | 14,752 | Median 3.2 years | Hazard ratio 0.91 (95 % CI 0.83 to 1.00); the trial did not meet its superiority threshold | 2017 |
| SCALE-PREDIABETESLiraglutide | Randomised, double-blind, placebo-controlled | 2,254 | 160 weeks | Onset in 2 % versus 6 % with placebo; hazard ratio 0.21 (95 % CI 0.13 to 0.34) | 2017 |
| SUSTAIN-1Semaglutide | Randomised, double-blind, placebo-controlled | 388 | 30 weeks | Reduction of 1.5 percentage points with 1.0 mg versus 0.0 with placebo | 2017 |
| 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: 74,597. 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 | 17 |
| Population outside the review question | 6 |
| Intervention outside the review question | 18 |
| Comparator not eligible | 10 |
| No eligible outcome reported | 7 |
| Duplicate report of an included study | 12 |
| Conference abstract without extractable data | 9 |
| Retracted or subject to an expression of concern | 9 |
| 88 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 |
|---|---|---|---|---|---|
| ESSENCE | Low | Low | Some | Low | Low |
| EXENATIDE-GE-PD | Low | Some | Low | Low | Low |
| STRIDE | Low | Low | Some | Low | Low |
| FLOW | Low | Low | Low | Low | Low |
| STEP-HFpEF-DM | Low | Low | Low | Low | Some |
| SELECT | Low | Low | Low | Low | Low |
| STEP-HFpEF | Low | Low | Low | Low | Some |
| STEP-5 | Low | Low | Low | Low | Low |
| STEP-8 | Low | Low | Low | Low | Low |
| STEP-TEENS | Some | Low | Low | Low | Low |
| AMPLITUDE-O | Low | Low | Low | Some | Low |
| STEP-1 | Low | Low | Low | Low | Low |
| STEP-2 | Low | Low | Low | Low | Low |
| STEP-3 | 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. | |||||
Compound Evidence Institute · CEI-ES-021/3 · https://compoundevidence.com/syntheses/thyroid-c-cell-signal/included-studies/ · retrieved 30 July 2026