Weight regain after discontinuation: difference between revisions
Diff·revision 4 → 5·18:31, 14 Oct 2024
Difference between revision 4 and revision 5 of Weight regain after discontinuation. 6 lines changed; the page grew by 978 bytes.
| Revision 4 — 07:05, 27 Sep 2024 AnaesthesiaAoife (talk) unpipe a link that did not need piping 1,814 bytes ±0 | Revision 5 — 18:31, 14 Oct 2024 AnaesthesiaAoife (talk) state whether the figure is from a trial or from post-marketing reporting 2,792 bytes +978 | ||
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| 10 | In [[STEP trial programme|STEP 4]], participants who had reached the maintenance dose during a 20-week run-in were randomised to continue or to switch to placebo. Those continuing lost further weight; those switched regained steadily over the following 48 weeks.{{r|rubino2021}} | 10 | In [[STEP trial programme|STEP 4]], participants who had reached the maintenance dose during a 20-week run-in were randomised to continue or to switch to placebo. Those continuing lost further weight; those switched regained steadily over the following 48 weeks.{{r|rubino2021}} |
| 11 | 11 | ||
| + | 12 | The finding is unsurprising given the mechanism. These agents act by producing a sustained pharmacological signal in the appetite-regulating system; removing the signal removes the effect, and the [[Arcuate nucleus|circuits]] return to their prior state rather than being reset by the period of treatment.{{r|drucker2018}} | |
| + | 13 | ||
| 12 | == What the withdrawal trials show == | 14 | == What the withdrawal trials show == |
| 13 | A randomised withdrawal design is necessary because an observational comparison of people who stop with people who continue is confounded: those who stop differ systematically, often having stopped because of intolerance or lack of response.{{r|rubino2021}} | 15 | A randomised withdrawal design is necessary because an observational comparison of people who stop with people who continue is confounded: those who stop differ systematically, often having stopped because of intolerance or lack of response.{{r|rubino2021}} |
| ⋮ | ⋮ | ||
| 15 | STEP 4 and SURMOUNT-4 both randomised after a lead-in on active treatment, so both groups had already lost weight and differed only in what followed. Regain in the withdrawn groups was substantial and progressive; neither trial ran long enough to establish whether weight returns fully to baseline.{{r|rubino2021}} | 17 | STEP 4 and SURMOUNT-4 both randomised after a lead-in on active treatment, so both groups had already lost weight and differed only in what followed. Regain in the withdrawn groups was substantial and progressive; neither trial ran long enough to establish whether weight returns fully to baseline.{{r|rubino2021}} |
| 16 | 18 | ||
| + | 19 | Cardiometabolic markers moved with weight. Improvements in blood pressure, lipids and glycaemia during the lead-in reversed on withdrawal, which argues that the benefits were weight-mediated rather than persistent effects of the exposure.{{r|wilding2021}} | |
| + | 20 | ||
| 17 | == References == | 21 | == References == |
| 18 | {{reflist}} | 22 | {{reflist}} |
| 19 | <ref name="rubino2021">Rubino D, Abrahamsson N, Davies M, et al. "Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance (STEP 4)." ''JAMA'' 325(14):1414–1425 (2021). PMID 33755728.</ref> | 23 | <ref name="rubino2021">Rubino D, Abrahamsson N, Davies M, et al. "Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance (STEP 4)." ''JAMA'' 325(14):1414–1425 (2021). PMID 33755728.</ref> |
| + | 24 | <ref name="drucker2018">Drucker DJ. "Mechanisms of action and therapeutic application of glucagon-like peptide-1." ''Cell Metabolism'' 27(4):740–756 (2018). PMID 29617641.</ref> | |
| + | 25 | <ref name="wilding2021">Wilding JPH, Batterham RL, Calanna S, et al. "Once-weekly semaglutide in adults with overweight or obesity." ''New England Journal of Medicine'' 384(11):989–1002 (2021). PMID 33567185.</ref> | |
| 20 | 26 | ||
| 21 | {{DEFAULTSORT:Weight regain after discontinuation}} | 27 | {{DEFAULTSORT:Weight regain after discontinuation}} |