Weight regain and cardiometabolic effects after withdrawal of semaglutide: The <scp>STEP</scp> 1 trial extension

Wilding, John; Batterham, Rachel L.; Davies, Melanie J.; Gaal, Luc F. Van; Kandler, Kristian; Konakli, Katerina; Lingvay, Ildiko; McGowan, Barbara; Oral, Tuğçe Kalaycı; Rosenstock, Julio; Wadden, Thomas A.; Wharton, Sean; Yokote, Koutaro; Kushner, Robert F.

doi:10.1111/dom.14725

Cited by 281 publications

(194 citation statements)

References 24 publications

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“…In contrast to findings with behavioral 20 – 22 and other pharmacological interventions 10 , 12 , 13 , the similar mean weight loss achieved with semaglutide 2.4 mg in STEP 5 at weeks 52 and 104 (–15.6% and –15.2%, respectively) suggests that, on average, there is minimal weight regain over 104 weeks when once-weekly semaglutide therapy is continued. When interpreted together with the findings of the STEP 4 withdrawal trial and STEP 1 off-treatment extension study, which both showed weight regain after semaglutide discontinuation (after 20 weeks’ treatment in STEP 4 and 68 weeks’ treatment in STEP 1) 23 , 24 , these results support the benefit of continued semaglutide treatment for sustained weight loss.…”

Section: Discussionmentioning

confidence: 55%

Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial

Garvey

Batterham²,

Bhatta³

et al. 2022

Nat Med

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263

226

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The STEP 5 trial assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo (both plus behavioral intervention) for long-term treatment of adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes. The co-primary endpoints were the percentage change in body weight and achievement of weight loss of ≥5% at week 104. Efficacy was assessed among all randomized participants regardless of treatment discontinuation or rescue intervention. From 5 October 2018 to 1 February 2019, 304 participants were randomly assigned to semaglutide 2.4 mg (n = 152) or placebo (n = 152), 92.8% of whom completed the trial (attended the end-of-trial safety visit). Most participants were female (236 (77.6%)) and white (283 (93.1%)), with a mean (s.d.) age of 47.3 (11.0) years, body mass index of 38.5 (6.9) kg m–2 and weight of 106.0 (22.0) kg. The mean change in body weight from baseline to week 104 was −15.2% in the semaglutide group (n = 152) versus −2.6% with placebo (n = 152), for an estimated treatment difference of −12.6 %-points (95% confidence interval, −15.3 to −9.8; P < 0.0001). More participants in the semaglutide group than in the placebo group achieved weight loss ≥5% from baseline at week 104 (77.1% versus 34.4%; P < 0.0001). Gastrointestinal adverse events, mostly mild-to-moderate, were reported more often with semaglutide than with placebo (82.2% versus 53.9%). In summary, in adults with overweight (with at least one weight-related comorbidity) or obesity, semaglutide treatment led to substantial, sustained weight loss over 104 weeks versus placebo. NCT03693430

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Section: Discussionmentioning

confidence: 55%

Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial

Garvey

Batterham²,

Bhatta³

et al. 2022

Nat Med

Self Cite

263

226

View full text Add to dashboard Cite

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“…Pharmacological activation of the widespread distribution of GLP‐1 receptors within the CNS, including the hypothalamus, promotes satiety and controls appetite and body weight 8 . Weight regain appears to be common upon cessation of treatment with semaglutide, 9 and long‐term weight loss maintenance is likely to require continuous use.…”

Section: Discussionmentioning

confidence: 99%

Weight loss with glucagon‐like peptide‐1 receptor agonists in Bardet‐Biedl syndrome

et al. 2022

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Summary Bardet–Biedl syndrome (BBS) is a rare genetic condition, characterized by ciliary protein dysfunction, leading to multi‐organ damage. People with BBS can develop early‐onset severe obesity and associated problems including the metabolic syndrome, type 2 diabetes and coronary heart disease. Weight management can be challenging with the lack of effective medical therapies so far. We report a patient with BBS who underwent successful weight reduction through the use of glucagon‐like peptide‐1 receptor agonists.

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“…Among 327 persons having BMI >30 kg/m 2 with at least one weight‐related comorbidity, but not having diabetes, treated with semaglutide 2.4 mg weekly vs. placebo for 68 weeks, 52 weeks after discontinuation of treatment the placebo group returned to baseline, and the semaglutide group, whose BMI had decreased from 37.6 to 31.2, had an increase in BMI to 35. Systolic and diastolic blood pressure, HbA1c, lipids, and C‐reactive protein all similarly returned toward or above baseline, 13 suggesting that such treatment likely is required in an ongoing fashion for persons with diabetes as well.…”

Section: Therapymentioning

confidence: 91%

Diabetes update: What's new, what's interesting

Bloomgarden

2022

Journal of Diabetes

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Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension

Cited by 281 publications

References 24 publications

Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial

Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial

Weight loss with glucagon‐like peptide‐1 receptor agonists in Bardet‐Biedl syndrome

Diabetes update: What's new, what's interesting

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