Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial

Kadowaki, Takashi; Isendahl, Joakim; Khalid, Usman; Lee, Sang Yeoup; Nishida, Tomoyuki; Ogawa, Wataru; Tobe, Kazuyuki; Yamauchi, Toshimasa; Lim, Soo

doi:10.1016/s2213-8587(22)00008-0

Cited by 158 publications

(167 citation statements)

References 25 publications

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“…The STEP 2 trial included individuals with type 2 diabetes mellitus and obesity [ 23 ]. In the STEP 6 trial, only 25% of the patients had diabetes [ 27 ]. Conversely, the STEP 1, 3, 4, 5, and 8 trials did not include patients with type 2 diabetes mellitus [ 22 , 24 , 25 , 26 , 28 ], which may explain the superior weight loss in STEP 1, 3–6, and 8.…”

Section: Discussionmentioning

confidence: 99%

“…However, only the STEP 3 trial incorporated very intensive lifestyle modifications, which included a low-calorie intake during the opening 8 weeks and then an additional 30 weeks of intensive behavioral therapy sessions with registered dieticians [ 24 ]. As a consequence, the patients in the placebo arm lost almost double the amount of weight recorded in the placebo arms of STEP 1, 2, 5, and 6 [ 22 , 23 , 26 , 27 ]. The placebo arm in STEP 3 lost 5.7% of weight, while the placebo arm in STEP 1 lost 2.4%, STEP 2 lost 3.4%, STEP 5 lost 2.6%, and STEP 6 lost 2.1%.…”

Section: Discussionmentioning

confidence: 99%

“…The STEP 6 trial (ClinicalTrials.gov identifier: NCT03811574) included east Asian adults, with or without type 2 diabetes, who reported a failed weight loss dietary attempt and had a BMI ≥ 27 kg/m 2 with two or more weight-related medical problems or a BMI ≥ 35 kg/m 2 with at least one weight-related medical problem [ 27 ]. The main exclusion criteria were previous or planned anti-obesity treatment or surgery and bodyweight changes of 5 kg or more in the past 3 months before screening.…”

Section: The Step 6 Trialmentioning

confidence: 99%

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The Impact Once-Weekly Semaglutide 2.4 mg Will Have on Clinical Practice: A Focus on the STEP Trials

2022

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Obesity is a complex and chronic disease that raises the risk of various complications. Substantial reduction in body weight improves these risk factors. Lifestyle changes, including physical activity, reduced caloric ingestion, and behavioral therapy, have been the principal pillars in the management of obesity. In recent years, pharmacologic interventions have improved remarkably. The Semaglutide Treatment Effect in People with Obesity (STEP) program is a collection of phase-III trials geared toward exploring the utility of once-weekly 2.4 mg semaglutide administered subcutaneously as a pharmacologic agent for patients with obesity. All the STEP studies included diet and exercise interventions but at different intensities. This review paper aims to explore the impact of the behavioral programs on the effect of semaglutide 2.4 mg on weight loss. The results of the STEP trials supported the efficacy of high-dose, once-weekly 2.4 mg semaglutide on body weight reduction among patients with obesity with/without diabetes mellitus. Semaglutide was associated with more gastrointestinal-related side effects compared to placebo but was generally safe and well tolerated. In all the STEP studies, despite the varying intestines of the behavioral programs, weight loss was very similar. For the first time, there may be a suggestion that these behavioral programs might not increase weight reduction beyond the effect of semaglutide. Nevertheless, the importance of nutritional support during substantial weight loss with pharmacotherapy needs to be re-evaluated.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: The Step 6 Trialmentioning

confidence: 99%

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The Impact Once-Weekly Semaglutide 2.4 mg Will Have on Clinical Practice: A Focus on the STEP Trials

2022

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“…Various parameters like weight loss, change in BMI, FPG, HbA1c, number of adverse events have been studied. A significant decline in weight was exhibited by 2.4 mg semaglutide (13.2%) and 1.7 mg semaglutide (9.6%) over 2.1% with placebo ( 46 ).…”

Section: Obesitymentioning

confidence: 98%

“…The long-term effects of semaglutide for management of chronic obesity couldn’t be studied in this study; whereas STEP-5 covers this aspect with a global population. Adherence to lifestyle intervention couldn’t be assessed in this study ( 46 ).…”

Section: Obesitymentioning

confidence: 99%

Therapeutic Potential of Semaglutide, a Newer GLP-1 Receptor Agonist, in Abating Obesity, Non-Alcoholic Steatohepatitis and Neurodegenerative diseases: A Narrative Review

Mahapatra

Karuppasamy²,

Sahoo

2022

Pharm Res

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Introduction Semaglutide, a peptidic GLP-1 receptor agonist, has been clinically approved for treatment of type 2 diabetes mellitus and is available in subcutaneous and oral dosage form. Diabetes, insulin resistance, and obesity are responsible for the pathological manifestations of non-alcoholic steatohepatitis (NASH). Similarly, insulin resistance in brain is also responsible for neurodegeneration and impaired cognitive functions. Background Observations from phase-3 clinical trials like SUSTAIN and PIONEER indicated anti-obesity potential of semaglutide, which was established in STEP trials. Various pre-clinical and phase-2 studies have indicated the therapeutic potential of semaglutide in non-alcoholic steatohepatitis and neurodegenerative disorders like Parkinson’s and Alzheimer’s disease. Discussion Significant weight reduction ability of semaglutide has been demonstrated in various phase-3 clinical trials, for which recently semaglutide became the first long-acting GLP-1 receptor agonist to be approved by the United States Food and Drug Administration for management of obesity. Various pre-clinical and clinical studies have revealed the hepatoprotective effect of semaglutide in NASH and neuroprotective effect in Parkinson’s and Alzheimer’s disease. Conclusion Many GLP-1 receptor agonists have shown hepatoprotective and neuroprotective activity in animal and human trials. As semaglutide is an already clinically approved drug, successful human trials would hasten its inclusion into therapeutic treatment of NASH and neurodegenerative diseases. Semaglutide improves insulin resistance, insulin signalling pathway, and reduce body weight which are responsible for prevention or progression of NASH and neurodegenerative diseases.

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Medications for Obesity

Gudzune,

Kushner

2024

JAMA

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ImportanceObesity affects approximately 19% of women and 14% of men worldwide and is associated with increased morbidity. Antiobesity medications (AOMs) modify biological processes that affect appetite and significantly improve outcomes, such as type 2 diabetes, hypertension, and dyslipidemia.ObservationsAOMs should be administered in combination with lifestyle interventions and can be classified according to their mechanisms of action. Orlistat modifies digestive tract absorption and causes gastrointestinal adverse effects, such as oily fecal spotting and urgency, in more than 25% of patients. Centrally acting drugs, such as phentermine-topiramate and naltrexone-bupropion, regulate appetite in the brain and are associated with constipation in approximately 20% of patients, although the incidence of other adverse effects (eg, paresthesia, nausea) varies by medication. Nutrient-stimulated hormone-based medications, such as liraglutide, semaglutide, and tirzepatide, mimic the actions of enteropancreatic hormones that modify central appetite regulation and provide multiple cardiometabolic weight-loss benefits. Adverse effects of these drugs include nausea (28%-44%), diarrhea (21%-30%), and constipation (11%-24%). The relative potency of adult obesity medications has been studied in meta-analyses. Compared with placebo, orlistat was associated with 3.1% greater weight loss (52 randomized clinical trials [RCTs]; 16 964 participants), phentermine-topiramate was associated with 8.0% greater weight loss (5 RCTs; 3407 participants), naltrexone-bupropion was associated with 4.1% greater weight loss (6 RCTs; 9949 participants), liraglutide was associated with 4.7% greater weight loss (18 RCTs; 6321 participants), semaglutide was associated with 11.4% greater weight loss (5 RCTs; 4421 participants), and tirzepatide 15 mg was associated with 12.4% greater weight loss (6 RCTs; 1972 participants).Conclusion and RelevanceObesity is associated with increased morbidity. Antiobesity medications are effective adjunctive therapy to lifestyle changes for improved weight loss and health outcomes.

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Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial

Cited by 158 publications

References 25 publications

The Impact Once-Weekly Semaglutide 2.4 mg Will Have on Clinical Practice: A Focus on the STEP Trials

The Impact Once-Weekly Semaglutide 2.4 mg Will Have on Clinical Practice: A Focus on the STEP Trials

Therapeutic Potential of Semaglutide, a Newer GLP-1 Receptor Agonist, in Abating Obesity, Non-Alcoholic Steatohepatitis and Neurodegenerative diseases: A Narrative Review

Medications for Obesity

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