Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial

Davies, Melanie J.; Færch, Louise; Jeppesen, Ole K.; Pakseresht, Arash; Pedersen, Sue D.; Perreault, Leigh; Rosenstock, Julio; Shimomura, Iichiro; Viljoen, Adie; Wadden, Thomas A.; Lingvay, Ildiko

doi:10.1016/s0140-6736(21)00213-0

Cited by 581 publications

(794 citation statements)

References 32 publications

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“…We have preliminary data that show that obese patients with T2D treated with high-dose Semaglutide 2.4 mg can achieve a reduction of approximately –9·6% and −15% of starting weight in patients with and without diabetes, respectively. 107 , 108 Of note, one-third of participants in this last study achieved 20% of weight loss similar to that obtained with sleeve gastrectomy (SG). The development of new drugs in the future for weight and glycemic control will be based on the combination of drugs like tirzepatide (dulaglutide plus a GIP analog), and combinations of GLP1, GIP, Glucagon coagonists/triagonists, combinations of Semaglutide and Pramlintide analog (Cagrilintide) and the YY peptide agonists.…”

Section: Treatment Of Obesity In T1d: Challenges and Opportunitiessupporting

confidence: 69%

Obesity in Patients with Type 1 Diabetes: Links, Risks and Management Challenges

Vilarrasa¹,

José²,

Rubio³

et al. 2021

DMSO

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Obesity affects large numbers of patients with type 1 diabetes (T1D) across their lifetime, with rates ranging between 2.8% and 37.1%. Patients with T1D and obesity are characterized by the presence of insulin resistance, of high insulin requirements, have a greater cardiometabolic risk and an enhanced risk of developing chronic complications when compared to normal-weight persons with T1D. Dual treatment of obesity and T1D is challenging and no specific guidelines for improving outcomes of both glycemic control and weight management have been established for this population. Nevertheless, although evidence is scarce, a comprehensive approach based on a balanced hypocaloric diet, physical activity and cognitive behavioral therapy by a multidisciplinary team, expert in both obesity and diabetes, remains as the best clinical practice. However, weight loss responses with lifestyle changes alone are limited, so in the “roadmap” of the treatment of obesity in T1D, it will be helpful to include anti-obesity pharmacotherapy despite at present there is a lack of evidence since T1D patients have been excluded from anti-obesity drug clinical trials. In case of severe obesity, bariatric surgery has proven to be of benefit in obtaining a substantial and long-term weight loss and reduction in cardiovascular risk. The near future looks promising with the development of new and more effective anti-obesity treatments and strategies to improve insulin resistance and oxidative stress. Advances in precision medicine may help individualize and optimize the medical management and care of these patients. This review, by gathering current evidence, highlights the need of solid knowledge in all facets of the treatment of patients with obesity and T1D that can only be obtained through high quality well-designed studies.

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Section: Treatment Of Obesity In T1d: Challenges and Opportunitiessupporting

confidence: 69%

Obesity in Patients with Type 1 Diabetes: Links, Risks and Management Challenges

Vilarrasa¹,

José²,

Rubio³

et al. 2021

DMSO

View full text Add to dashboard Cite

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“…The mean reduction in body weight from baseline to week 68 was 9.6%-16.0% in the semaglutide group versus 2.4%-5.7% with placebo, across the STEP 1-3 trials [90,91,93]. Although direct cross-study comparisons of liraglutide and semaglutide should be interpreted with caution, compared with liraglutide (6%-8%), semaglutide appears to have greater weight-reducing potential.…”

Section: Use Of Other Glp-1 Ra Therapy In Obesitymentioning

confidence: 88%

“…The safety and efficacy of once-weekly-administered semaglutide 2.4 mg for obesity have been assessed and published in four phase 3, 68-week trials (STEP clinical program) [90][91][92][93]. The STEP 1 trial focused on the use of semaglutide 2.4 mg as an adjunct to lifestyle intervention [90].…”

Section: Use Of Other Glp-1 Ra Therapy In Obesitymentioning

confidence: 99%

“…The STEP 1 trial focused on the use of semaglutide 2.4 mg as an adjunct to lifestyle intervention [90]. STEP 2 compared semaglutide 2.4 mg versus 1.0 mg versus placebo [93]. STEP 3 explored the efficacy of semaglutide 2.4 mg versus placebo, both combined with IBT [91].…”

Section: Use Of Other Glp-1 Ra Therapy In Obesitymentioning

confidence: 99%

“…STEP 4 compared continued treatment with semaglutide 2.4 mg versus switch to placebo [92]. Only STEP 2 enrolled patients with T2D [93].…”

Section: Use Of Other Glp-1 Ra Therapy In Obesitymentioning

confidence: 99%

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Patient initiation and maintenance of GLP-1 RAs for treatment of obesity

Patel

Smith

2021

Expert Review of Clinical Pharmacology

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Introduction: Healthcare providers (HCPs) see many patients with obesity-related complications and are therefore well placed to help treat obesity itself. However, limited collated information exists to help HCPs with the practical use of anti-obesity medications (AOMs). We focus on the initiation and maintenance of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) for weight management, liraglutide 3.0 mg. Literature search was conducted between 25-28 November 2019 on PubMed and ClinicalTrials.gov. Areas covered: Clinical trial and real-world data describing weight-loss efficacy, cardiometabolic risk factors, incidence of adverse events (AEs), and persistence are presented to assist HCPs with patient discussions. Practical considerations to overcome barriers to optimal use are provided, equipping HCPs with the information required to aid with adherence to and persistence with AOMs. The use of other GLP-1-RA therapies in obesity is discussed in light of the recent US Food and Drug Administration approval of semaglutide 2.4 mg for weight management. Expert opinion: Liraglutide 3.0 mg provides benefits regarding weight loss and improvements in cardiometabolic risk factors. Promising areas of future research in the field of obesity include dual receptor agonists and the combination of glucagon-like peptide-1 receptor agonists with other molecules.

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Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes

Rubino

Greenway

Khalid

et al. 2022

JAMA

Self Cite

435

385

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IMPORTANCE Phase 3 trials have not compared semaglutide and liraglutide, glucagon-like peptide-1 analogues available for weight management.OBJECTIVE To compare the efficacy and adverse event profiles of once-weekly subcutaneous semaglutide, 2.4 mg, vs once-daily subcutaneous liraglutide, 3.0 mg (both with diet and physical activity), in people with overweight or obesity. DESIGN, SETTING, AND PARTICIPANTS Randomized, open-label, 68-week, phase 3b trial conducted at 19 US sites from September 2019 (enrollment: September 11-November 26) to May 2021 (end of follow-up: May 11) in adults with body mass index of 30 or greater or 27 or greater with 1 or more weight-related comorbidities, without diabetes (N = 338).INTERVENTIONS Participants were randomized (3:1:3:1) to receive once-weekly subcutaneous semaglutide, 2.4 mg (16-week escalation; n = 126), or matching placebo, or once-daily subcutaneous liraglutide, 3.0 mg (4-week escalation; n = 127), or matching placebo, plus diet and physical activity. Participants unable to tolerate 2.4 mg of semaglutide could receive 1.7 mg; participants unable to tolerate 3.0 mg of liraglutide discontinued treatment and could restart the 4-week titration. Placebo groups were pooled (n = 85). MAIN OUTCOMES AND MEASURESThe primary end point was percentage change in body weight, and confirmatory secondary end points were achievement of 10% or more, 15% or more, and 20% or more weight loss, assessed for semaglutide vs liraglutide at week 68. Semaglutide vs liraglutide comparisons were open-label, with active treatment groups double-blinded against matched placebo groups. Comparisons of active treatments vs pooled placebo were supportive secondary end points. RESULTSOf 338 randomized participants (mean [SD] age, 49 [13] years; 265 women [78.4%]; mean [SD] body weight, 104.5 [23.8] kg; mean [SD] body mass index, 37.5 [6.8]), 319 (94.4%) completed the trial, and 271 (80.2%) completed treatment. The mean weight change from baseline was -15.8% with semaglutide vs -6.4% with liraglutide (difference, -9.4 percentage points [95% CI, -12.0 to -6.8]; P < .001); weight change with pooled placebo was -1.9%. Participants had significantly greater odds of achieving 10% or more, 15% or more, and 20% or more weight loss with semaglutide vs liraglutide (70.9% of participants vs 25.6% [odds ratio, 6.3 {95% CI, 3.5 to 11.2}], 55.6% vs 12.0% [odds ratio, 7.9 {95% CI, 4.1 to 15.4}], and 38.5% vs 6.0% [odds ratio, 8.2 {95% CI, 3.5 to 19.1}], respectively; all P < .001). Proportions of participants discontinuing treatment for any reason were 13.5% with semaglutide and 27.6% with liraglutide. Gastrointestinal adverse events were reported by 84.1% with semaglutide and 82.7% with liraglutide.CONCLUSIONS AND RELEVANCE Among adults with overweight or obesity without diabetes, once-weekly subcutaneous semaglutide compared with once-daily subcutaneous liraglutide, added to counseling for diet and physical activity, resulted in significantly greater weight loss at 68 weeks.

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Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial

Cited by 581 publications

References 32 publications

Obesity in Patients with Type 1 Diabetes: Links, Risks and Management Challenges

Obesity in Patients with Type 1 Diabetes: Links, Risks and Management Challenges

Patient initiation and maintenance of GLP-1 RAs for treatment of obesity

Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes

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