The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity.
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ABSTRACT: Aim
To investigate the effects of once-weekly subcutaneous (s.c.) semaglutide 2.4 mg on gastric emptying, appetite, and energy intake in adults with obesity.Materials and methods
A double-blind, parallel-group trial was conducted in 72 adults with obesity, randomized to once-weekly s.c. semaglutide (dose-escalated to 2.4 mg) or placebo for 20?weeks. Gastric emptying was assessed using paracetamol absorption following a standardized breakfast. Participant-reported appetite ratings and Control of Eating Questionnaire (CoEQ) responses were assessed, and energy intake was measured during ad libitum lunch.Results
The area under the concentration-time curve (AUC) for paracetamol 0 to 5 hours after a standardized meal (AUC0-5h,para ; primary endpoint) was increased by 8% (P =?0.005) with semaglutide 2.4 mg versus placebo at week 20 (non-significant when corrected for week 20 body weight; P =?0.12). No effect was seen on AUC0-1h,para , maximum observed paracetamol concentration, or time to maximum observed paracetamol concentration. Ad libitum energy intake was 35% lower with semaglutide versus placebo (1736 versus 2676?kJ; estimated treatment difference -940?kJ; P <0.0001). Semaglutide reduced hunger and prospective food consumption, and increased fullness and satiety when compared with placebo (all P <0.02). The CoEQ indicated better control of eating and fewer/weaker food cravings with semaglutide versus placebo (P <0.05). Body weight was reduced by 9.9% with semaglutide and 0.4% with placebo. Safety was consistent with the known profile of semaglutide.Conclusions
In adults with obesity, once-weekly s.c. semaglutide 2.4 mg suppressed appetite, improved control of eating, and reduced food cravings, ad libitum energy intake and body weight versus placebo. There was no evidence of delayed gastric emptying at week 20, assessed indirectly via paracetamol absorption.
SUBMITTER: Friedrichsen M
PROVIDER: S-EPMC7898914 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
Publications
The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity.
Friedrichsen Martin M Breitschaft Astrid A Tadayon Sayeh S Wizert Alicja A Skovgaard Dorthe D
Diabetes, obesity & metabolism 20210103 3
<h4>Aim</h4>To investigate the effects of once-weekly subcutaneous (s.c.) semaglutide 2.4 mg on gastric emptying, appetite, and energy intake in adults with obesity.<h4>Materials and methods</h4>A double-blind, parallel-group trial was conducted in 72 adults with obesity, randomized to once-weekly s.c. semaglutide (dose-escalated to 2.4 mg) or placebo for 20 weeks. Gastric emptying was assessed using paracetamol absorption following a standardized breakfast. Participant-reported appetite ratings ...[more]
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Project description:The treatment of obesity can no longer be reduced to a simplistic view of weight loss. Metabolic adaptation leads to systematic weight regain following weight-loss efforts, and new obesity treatments should therefore aim to induce long-standing double-digit weight loss, and thus improve and even reverse obesity-associated comorbidities such as type 2 diabetes. Until now, only metabolic surgery has been able to achieve such a goal, but this invasive procedure cannot be offered on a large scale. Among the alternatives, lifestyle interventions and drug therapies have often been disappointing. The recent availability of once-weekly subcutaneous 2.4 mg semaglutide (a glucagon-like peptide-1 receptor agonist; Wegovy™ Novo Nordisk A/S, Bagsværd, Denmark) has changed the scene, and semaglutide is considered a 'game changer' in the treatment of obesity. The results from the phase III STEP (Semaglutide treatment effect in people with obesity) clinical programme have shown that semaglutide provides clinically meaningful and sustained weight loss in ranges much higher than those achieved with previously available pharmacotherapies. These results led to the approval of semaglutide by regulatory authorities as an adjunct to a reduced-calorie diet and increased physical activity in people with obesity or overweight, with at least one weight-related comorbidity. With data from phase II and III clinical trials showing that newer drugs (i.e. the glucagon-like peptide-1 and gastric inhibitory polypeptide dual receptor agonist tirzepatide and the amylin agonist cagrilintide, either alone or combined) produce a greater sustained weight loss than semaglutide, an upstream 'weight-centric' strategy has emerged as a new standard for the treatment of type 2 diabetes.
| S-EPMC9354513 | biostudies-literature
Project description:AimThe aim of this trial was to investigate the mechanism of action for body weight loss with semaglutide.Materials and methodsThis randomised, double-blind, placebo-controlled, two-period crossover trial investigated the effects of 12 weeks of treatment with once-weekly subcutaneous semaglutide, dose-escalated to 1.0 mg, in 30 subjects with obesity. Ad libitum energy intake, ratings of appetite, thirst, nausea and well-being, control of eating, food preference, resting metabolic rate, body weight and body composition were assessed.ResultsAfter a standardised breakfast, semaglutide, compared with placebo, led to a lower ad libitum energy intake during lunch (-1255 kJ; P < .0001) and during the subsequent evening meal ( P = .0401) and snacks ( P = .0034), resulting in a 24% reduction in total energy intake across all ad libitum meals throughout the day (-3036 kJ; P < .0001). Fasting overall appetite suppression scores were improved with semaglutide vs placebo, while nausea ratings were similar. Semaglutide was associated with less hunger and food cravings, better control of eating and a lower preference for high-fat foods. Resting metabolic rate, adjusted for lean body mass, did not differ between treatments. Semaglutide led to a reduction from baseline in mean body weight of 5.0 kg, predominantly from body fat mass.ConclusionAfter 12 weeks of treatment, ad libitum energy intake was substantially lower with semaglutide vs placebo with a corresponding loss of body weight observed with semaglutide. In addition to reduced energy intake, likely mechanisms for semaglutide-induced weight loss included less appetite and food cravings, better control of eating and lower relative preference for fatty, energy-dense foods.
| S-EPMC5573908 | biostudies-literature
Project description:Abstract Background: Despite the increasing global adverse health impact of obesity, there are few pharmacological options for effective weight management. STEP 1 investigated the efficacy and safety of the glucagon-like peptide-1 analogue, subcutaneous (s.c.) semaglutide, for weight management in adults with overweight or obesity. Methods: This randomized, double-blind, placebo-controlled, phase 3 trial was conducted at 129 sites across 16 countries (NCT03548935). Adults aged ≥18 years with either body mass index (BMI) ≥30 kg/m2 or BMI ≥27 kg/m2 with ≥1 weight-related comorbidity, without type 2 diabetes, were randomized 2:1 to 68 weeks’ treatment with once-weekly s.c. semaglutide 2.4 mg or placebo, both as adjunct to lifestyle intervention. The co-primary endpoints were percentage change in body weight and achievement of weight loss ≥5%. Cardiometabolic risk factors, patient-reported outcomes, and safety/tolerability were also assessed. Two estimands were defined: treatment policy (effect regardless of treatment adherence and use of rescue intervention) and trial product (effect assuming treatment adherence and without rescue intervention); results are presented for the treatment policy estimand, unless stated otherwise. P values for parameters marked with # were not controlled for multiplicity. Results: 1961 randomized participants (mean age 46 years, body weight 105.3 kg, BMI 37.9 kg/m2; 74.1% female) were included. Mean body weight change from baseline to week 68 was −14.9% in the semaglutide group vs −2.4% with placebo (estimated treatment difference [ETD]: −12.4%; 95% confidence interval (CI): −13.4, −11.5; p<0.0001). Similar results were obtained with the trial product estimand: mean body weight change# was -16.9% for semaglutide vs -2.4% for placebo (ETD: -14.4%; 95% CI: -15.3, -13.6; p<0.0001). Participants were more likely to achieve weight loss ≥5%, ≥10%, ≥15%, and ≥20%# with semaglutide vs placebo (86.4% vs 31.5%, 69.1% vs 12.0%, 50.5% vs 4.9%, and 32.0% vs 1.7%, respectively; p<0.0001 for all). Greater improvements were seen with semaglutide vs placebo in waist circumference, BMI#, systolic and diastolic# blood pressure, glycated hemoglobin#, fasting plasma glucose#, C-reactive protein#, fasting lipid profile#, and self-reported physical functioning (p<0.05 for all). No new safety signals with semaglutide were observed. The most frequent adverse events with semaglutide were gastrointestinal disorders (typically transient and mild-to-moderate). Conclusion: In adults with overweight or obesity, once-weekly s.c. semaglutide 2.4 mg plus lifestyle intervention induced a mean weight loss of approximately 15% by week 68. Clinically beneficial weight loss of ≥10% was achieved by over two-thirds of participants and ≥20% by one-third of participants, along with associated improvements in cardiometabolic risk factors and physical functioning.
| S-EPMC8089593 | biostudies-literature
Project description: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.
| S-EPMC9182751 | biostudies-literature
Project description:Abstract Background: In people with overweight or obesity, long-term maintenance of weight loss is challenging. Subcutaneous (s.c.) semaglutide, a glucagon-like peptide-1 analogue, has shown clinically-relevant weight loss in a phase 2 trial in people with obesity. STEP 4 investigated the impact of continued semaglutide 2.4 mg treatment, vs switching to placebo, on maintenance of weight loss in participants who reached 2.4 mg of semaglutide during a run-in period. Methods: This was a 68-week withdrawal trial (NCT03548987) in 902 subjects aged ≥18 years with body mass index (BMI) ≥30 kg/m2 (or BMI ≥27 kg/m2 with ≥1 weight-related comorbidity), without diabetes. Following a 20 week run-in period, 803 subjects who reached the maintenance dose of once-weekly (OW) s.c. semaglutide 2.4 mg were randomized 2:1 to continue treatment with semaglutide 2.4 mg or switch to placebo for 48 weeks, both as adjunct to lifestyle intervention. The primary endpoint was percentage change in body weight between randomization (week 20) and week 68. Confirmatory secondary endpoints included change in waist circumference and systolic blood pressure. Two estimands were defined: treatment policy and trial product; results are presented for the treatment policy estimand, unless stated otherwise. Results: Mean body weight (±SD) was 107.2 ±22.7 kg at week 0 and 96.1 ±22.6 kg at randomization (week 20; mean change -10.6%). Randomized participants were mostly female (79%) and white (84%); mean age was 46 years and mean BMI was 34.4 kg/m2. Between weeks 20–68, estimated mean body weight change was −7.9% vs +6.9% for semaglutide 2.4 mg vs placebo (estimated treatment difference [ETD]: −14.8%; 95% confidence interval [CI]: −16.0, −13.5; p<0.0001), and -8.8% vs 6.5%, respectively, for the trial product estimand (ETD: -15.3%; 95% CI: -16.5, -14.1; p<0.0001). For participants randomized to continue semaglutide, the estimated change in body weight from week 0–68 was -17.4% (-18.2% for trial product estimand). Continued semaglutide treatment (weeks 20–68) led to clinically-relevant improvements in waist circumference, systolic blood pressure, BMI, HbA1c, FPG, and lipids (total cholesterol, LDL, VLDL, and triglycerides) vs switching to placebo (p<0.0001 for all). During the run-in period, 5.3% of participants discontinued treatment due to adverse events; during the randomized period, 2.4% (semaglutide) and 2.2% (placebo) discontinued. Nausea, diarrhea and constipation (mostly transient and mild-to-moderate) were the most frequent adverse events with semaglutide. Conclusion: In adults with overweight or obesity, continued treatment after dose escalation with OW s.c. semaglutide 2.4 mg until week 68 led to clinically-relevant weight loss, while switching to placebo led to significant weight regain; these data underscore the chronicity and relapsing nature of obesity, and the need for continued treatment.
| S-EPMC8089318 | biostudies-literature
Project description:Abstract Background: Semaglutide is a long-acting, subcutaneous (s.c.), glucagon-like peptide-1 analogue that is currently being investigated for obesity management in adults with overweight or obesity in the phase 3 STEP clinical trial program. Varying degrees of weight loss were observed with once-weekly s.c. semaglutide 2.4 mg in STEP 1, and a post-hoc analysis was conducted to investigate weight loss in subgroups of participants based on their baseline characteristics. Methods: STEP 1 was a randomized, double-blind, placebo-controlled, phase 3 trial (NCT03548935). Adults aged ≥18 years with either body mass index (BMI) ≥27 kg/m2 with ≥1 weight-related comorbidity or BMI ≥30 kg/m2, without type 2 diabetes, were randomized 2:1 to 68 weeks’ treatment with once-weekly s.c. semaglutide 2.4 mg or placebo, as adjunct to lifestyle intervention. A descriptive evaluation of categorical weight loss with semaglutide from baseline to week 68 (≥20%, 15-<20%, 10-<15%, 5-<10%) by baseline characteristics (age, sex, race [White, Asian, Black or African American, other], body weight, BMI, waist circumference, and glycemic status [normo-glycemia, pre-diabetes]) was conducted. Mean percent weight loss with semaglutide from baseline to week 68 was analyzed separately by sex (male, female) and baseline body weight (≥115 kg, 100-<115 kg, 90-<100 kg, <90 kg) using a mixed model for repeated measurements analysis with treatment, subgroup (of sex or baseline body weight), and the interaction between treatment and subgroup as factors, and baseline body weight as a covariate, all nested within visit (based on the trial product estimand [treatment effect assuming treatment adherence and without use of rescue intervention] for the on-treatment period). Results: STEP 1 included 1,961 randomized participants (mean age 46 years, body weight 105.3 kg, BMI 37.9 kg/m2; 74.1% female). For categorical weight loss, the observed proportions of participants with ≥20%, 15-<20%, 10-<15%, and 5-<10% weight loss at week 68 were 34.8%, 19.9%, 20.0%, and 17.5% with semaglutide vs 2.0%, 3.0%, 6.8%, and 21.2% with placebo, respectively. The distribution of participants across weight loss groups did not appear to be affected by any baseline characteristics, except sex and baseline body weight. Mean percent weight loss at week 68 with semaglutide was greater among females than males, and in participants with lower vs higher baseline body weight. Sex and baseline body weight were independently associated with weight loss with semaglutide vs placebo at week 68 (p<0.001 for both tests for subgroup interactions). Conclusion: In STEP 1, weight loss with once-weekly s.c. semaglutide 2.4 mg was seen in all subgroups evaluated, and was generally not influenced by baseline characteristics. The exception was sex and baseline body weight; female sex and a low baseline body weight were associated with a greater response to semaglutide.
| S-EPMC8089676 | biostudies-literature
Project description:Abstract Background: In people with overweight/obesity and type 2 diabetes (T2D), achievement of weight loss can be a challenge. STEP 2 investigated the efficacy and safety of semaglutide 2.4 mg for weight management in adults with overweight/obesity and T2D. Methods: This randomized, double-blind, double-dummy, placebo-controlled, phase 3 trial was conducted at 149 sites across 12 countries (NCT03552757). Adults aged ≥18 years with body mass index (BMI) ≥27 kg/m2, T2D, HbA1c between 7–10% (53–86 mmol/mol), and receiving ≤3 oral glucose-lowering agents were randomized 1:1:1 to once-weekly subcutaneous (s.c.) semaglutide 2.4 mg or 1.0 mg, or placebo, as adjunct to a reduced-calorie diet and increased physical activity for 68 weeks. The co-primary endpoints were percentage change in body weight and proportion of participants achieving weight loss ≥5% for semaglutide 2.4 mg vs placebo. Cardiovascular risk factors, glycemia and safety/tolerability were also assessed. Two estimands were defined: treatment policy and trial product; results are presented for the treatment policy estimand, unless stated otherwise. Results: 1,210 participants (mean: age 55 years, body weight 99.8 kg, BMI 35.7 kg/m2, HbA1c 8.1%, diabetes duration 8.0 years; 50.9% female) were randomized. Mean body weight change from baseline to week 68 was −9.6% with semaglutide 2.4 mg vs −3.4% with placebo (estimated treatment difference [ETD]: −6.2%; 95% confidence interval [CI]: −7.3, −5.2; p<0.0001) and −7.0% for semaglutide 1.0 mg (ETD for semaglutide 2.4 mg vs 1.0 mg: −2.7%; 95% CI: −3.7, −1.6; p<0.0001). Similar results were obtained with the trial product estimand: mean body weight change −10.6% for semaglutide 2.4 mg vs −3.1% for placebo (ETD: −7.6%; 95% CI: −8.6, −6.6; p<0.0001) and 7.6% for semaglutide 1.0 mg (ETD vs semaglutide 2.4 mg: −3.1%; 95% CI: −4.1, −2.1; p<0.0001). Participants on semaglutide 2.4 mg were more likely to achieve weight loss ≥5%, ≥10%, ≥15% and ≥20% vs placebo (68.8% vs 28.5%, 45.6% vs 8.2%, 25.8% vs 3.2% and 13.1% vs 1.6%, respectively; p value for odds ratios <0.0001 for all). Mean change in HbA1c from baseline to week 68 was −1.6% for semaglutide 2.4 mg vs −0.4% for placebo (p<0.0001). Greater improvements with semaglutide 2.4 mg vs placebo were also seen in waist circumference, BMI, systolic blood pressure, fasting plasma glucose, C-reactive protein, and lipids (HDL, VLDL, free fatty acids, and triglycerides) (p<0.05 for all). The most frequent adverse events were gastrointestinal disorders (typically transient and mild-to-moderate), occurring in 57.5%, 63.5% and 34.3% of participants receiving semaglutide 1.0 mg, 2.4 mg and placebo, respectively. Conclusion: Semaglutide 2.4 mg, as adjunct to lifestyle intervention, was efficacious and well tolerated for weight management in adults with overweight or obesity and T2D, providing significantly greater weight loss vs placebo and semaglutide 1.0 mg at week 68.
| S-EPMC8089158 | biostudies-literature
Project description:Abstract Background: Semaglutide, a glucagon-like peptide-1 analogue, is being investigated in people with overweight or obesity. A post-hoc analysis of the STEP 4 trial was conducted to identify whether early weight loss is predictive of later weight loss with maintenance once-weekly subcutaneous (s.c.) semaglutide 2.4 mg. Methods: STEP 4 was a randomized, double-blind, phase 3 withdrawal trial (NCT03548987). Adults aged ≥18 years with either body mass index (BMI) ≥27 kg/m2 with ≥1 weight-related comorbidity or BMI ≥30 kg/m2, without type 2 diabetes, underwent a 20-week run-in period. Participants reaching the maintenance dose of once-weekly s.c. semaglutide 2.4 mg at week 20 (regardless of weight loss achieved) were randomized 2:1 to semaglutide 2.4 mg or placebo, as adjunct to lifestyle intervention, for an additional 48 weeks. Percent change in body weight from week 0 to 68 was estimated using a mixed model for repeated measurements analysis with treatment, week 20 responder status, and the interaction between treatment and week 20 responder status as factors, and baseline body weight as a covariate, all nested within visit (based on the trial product estimand [treatment effect assuming treatment adherence and without use of rescue intervention] for the on-treatment period). Participants were considered responders if they achieved ≥5% weight loss at week 20. Whether the week 20 response to semaglutide predicted the achievement of clinically-relevant weight loss (≥5%) by week 68 was also assessed. Results: In STEP 4, 902 participants initiated semaglutide at week 0, of whom 803 were randomized at week 20 (semaglutide: n=535, placebo: n=268; characteristics at week 0 for all randomized participants: mean age 46 years, body weight 107.2 kg, BMI 38.4 kg/m2; 79.0% female; 83.7% white). For the 88.0% of participants randomized to semaglutide and who were responders at week 20, mean body weight change from week 0 to 68 was -19.7%. For non-responders at week 20, mean body weight change was -6.4% with continued semaglutide vs -0.3% with switch to placebo. Of all participants randomized to semaglutide, 86.2% achieved a clinically-relevant weight loss (≥5%) at week 68. Being a responder at week 20 was highly predictive of achieving this outcome (positive predictive value: 96.4%), whereas being a non-responder at week 20 had limited predictive value (negative predictive value: 42.9%). Conclusion: In the STEP 4 trial, the vast majority of participants who were randomized to the maintenance dose of once-weekly s.c. semaglutide 2.4 mg at week 20 had lost ≥5% body weight by week 68, with most achieving this by week 20. Overall weight loss with semaglutide was greater among early responders, but non-responders also achieved a clinically-relevant weight loss by week 68 if semaglutide treatment was continued.
| S-EPMC8265765 | biostudies-literature
Project description:Background: In people with overweight/obesity and type 2 diabetes (T2D), achievement of weight loss can be a challenge. STEP 2 investigated the efficacy and safety of semaglutide 2.4 mg for weight management in adults with overweight/obesity and T2D. Methods: This randomized, double-blind, double-dummy, placebo-controlled, phase 3 trial was conducted at 149 sites across 12 countries (NCT03552757). Adults aged ≥18 years with body mass index (BMI) ≥27 kg/m2, T2D, HbA1c between 7–10% (53–86 mmol/mol), and receiving ≤3 oral glucose-lowering agents were randomized 1:1:1 to once-weekly subcutaneous (s.c.) semaglutide 2.4 mg or 1.0 mg, or placebo, as adjunct to a reduced-calorie diet and increased physical activity for 68 weeks. The co-primary endpoints were percentage change in body weight and proportion of participants achieving weight loss ≥5% for semaglutide 2.4 mg vs placebo. Cardiovascular risk factors, glycemia and safety/tolerability were also assessed. Two estimands were defined: treatment policy and trial product; results are presented for the treatment policy estimand, unless stated otherwise. Results: 1,210 participants (mean: age 55 years, body weight 99.8 kg, BMI 35.7 kg/m2, HbA1c 8.1%, diabetes duration 8.0 years; 50.9% female) were randomized. Mean body weight change from baseline to week 68 was −9.6% with semaglutide 2.4 mg vs −3.4% with placebo (estimated treatment difference [ETD]: −6.2%; 95% confidence interval [CI]: −7.3, −5.2; p<0.0001) and −7.0% for semaglutide 1.0 mg (ETD for semaglutide 2.4 mg vs 1.0 mg: −2.7%; 95% CI: −3.7, −1.6; p<0.0001). Similar results were obtained with the trial product estimand: mean body weight change −10.6% for semaglutide 2.4 mg vs −3.1% for placebo (ETD: −7.6%; 95% CI: −8.6, −6.6; p<0.0001) and 7.6% for semaglutide 1.0 mg (ETD vs semaglutide 2.4 mg: −3.1%; 95% CI: −4.1, −2.1; p<0.0001). Participants on semaglutide 2.4 mg were more likely to achieve weight loss ≥5%, ≥10%, ≥15% and ≥20% vs placebo (68.8% vs 28.5%, 45.6% vs 8.2%, 25.8% vs 3.2% and 13.1% vs 1.6%, respectively; p value for odds ratios <0.0001 for all). Mean change in HbA1c from baseline to week 68 was −1.6% for semaglutide 2.4 mg vs −0.4% for placebo (p<0.0001). Greater improvements with semaglutide 2.4 mg vs placebo were also seen in waist circumference, BMI, systolic blood pressure, fasting plasma glucose, C-reactive protein, and lipids (HDL, VLDL, free fatty acids, and triglycerides) (p<0.05 for all). The most frequent adverse events were gastrointestinal disorders (typically transient and mild-to-moderate), occurring in 57.5%, 63.5% and 34.3% of participants receiving semaglutide 1.0 mg, 2.4 mg and placebo, respectively. Conclusion: Semaglutide 2.4 mg, as adjunct to lifestyle intervention, was efficacious and well tolerated for weight management in adults with overweight or obesity and T2D, providing significantly greater weight loss vs placebo and semaglutide 1.0 mg at week 68.
| S-EPMC9067799 | biostudies-literature
Project description:Background: Semaglutide is a long-acting, subcutaneous (s.c.), glucagon-like peptide-1 analogue that is currently being investigated for obesity management in adults with overweight or obesity in the phase 3 STEP clinical trial program. Varying degrees of weight loss were observed with once-weekly s.c. semaglutide 2.4 mg in STEP 1, and a post-hoc analysis was conducted to investigate weight loss in subgroups of participants based on their baseline characteristics. Methods: STEP 1 was a randomized, double-blind, placebo-controlled, phase 3 trial (NCT03548935). Adults aged ≥18 years with either body mass index (BMI) ≥27 kg/ m2 with ≥1 weight-related comorbidity or BMI ≥30 kg/m2, without type 2 diabetes, were randomized 2:1 to 68 weeks’ treatment with once-weekly s.c. semaglutide 2.4 mg or placebo, as adjunct to lifestyle intervention. A descriptive evaluation of categorical weight loss with semaglutide from baseline to week 68 (≥20%, 15-<20%, 10-<15%, 5-<10%) by baseline characteristics (age, sex, race [White, Asian, Black or African American, other], body weight, BMI, waist circumference, and glycemic status [normo-glycemia, pre-diabetes]) was conducted. Mean percent weight loss with semaglutide from baseline to week 68 was analyzed separately by sex (male, female) and baseline body weight (≥115 kg, 100-<115 kg, 90-<100 kg, <90 kg) using a mixed model for repeated measurements analysis with treatment, subgroup (of sex or baseline body weight), and the interaction between treatment and subgroup as factors, and baseline body weight as a covariate, all nested within visit (based on the trial product estimand [treatment effect assuming treatment adherence and without use of rescue intervention] for the on-treatment period). Results: STEP 1 included 1,961 randomized participants (mean age 46 years, body weight 105.3 kg, BMI 37.9 kg/ m2; 74.1% female). For categorical weight loss, the observed proportions of participants with ≥20%, 15-<20%, 10-<15%, and 5-<10% weight loss at week 68 were 34.8%, 19.9%, 20.0%, and 17.5% with semaglutide vs 2.0%, 3.0%, 6.8%, and 21.2% with placebo, respectively. The distribution of participants across weight loss groups did not appear to be affected by any baseline characteristics, except sex and baseline body weight. Mean percent weight loss at week 68 with semaglutide was greater among females than males, and in participants with lower vs higher baseline body weight. Sex and baseline body weight were independently associated with weight loss with semaglutide vs placebo at week 68 (p<0.001 for both tests for subgroup interactions). Conclusion: In STEP 1, weight loss with once-weekly s.c. semaglutide 2.4 mg was seen in all subgroups evaluated, and was generally not influenced by baseline characteristics. The exception was sex and baseline body weight; female sex and a low baseline body weight were associated with a greater response to semaglutide.
| S-EPMC9067867 | biostudies-literature