Efficacy and safety of once‐weekly semaglutide versus once‐daily sitagliptin as add‐on to metformin in patients with type 2 diabetes in <scp>SUSTAIN China</scp>: A 30‐week, double‐blind, phase 3a, randomized trial

Ji, Linong; Dong, Xiaolin; Li, Yiming; Li, Yufeng; Lim, Soo; Liu, Ming; Zu, Ning; Rasmussen, Søren; Skjøth, Trine Vang; Yuan, Guoyue; Eliaschewitz, Freddy Goldberg

doi:10.1111/dom.14232

Cited by 57 publications

(73 citation statements)

References 37 publications

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“…Both the subcutaneous and oral formulations of semaglutide have undergone extensive phase 3 clinical testing ( Table 1 ). For the once-weekly subcutaneous formulation, the SUSTAIN program (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes) included 13 separate randomized clinical phase 3a and 3b trials ( 10 – 13 , 22 , 25 – 32 ) SUSTAIN 1 through 10 were global international trials, while three additional trials were specific for China and Japan. In four studies, semaglutide was compared with placebo, with differing patient populations.…”

Section: Semaglutidementioning

confidence: 99%

Safety of Semaglutide

2021

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The glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide is the most recently approved agent of this drug class, and the only GLP-1RA currently available as both subcutaneous and oral formulation. While GLP-1RAs effectively improve glycemic control and cause weight loss, potential safety concerns have arisen over the years. For semaglutide, such concerns have been addressed in the extensive phase 3 registration trials including cardiovascular outcome trials for both subcutaneous (SUSTAIN: Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes) and oral (PIONEER: Peptide InnOvatioN for the Early diabEtes tReatment) semaglutide and are being studied in further trials and registries, including real world data studies. In the current review we discuss the occurrence of adverse events associated with semaglutide focusing on hypoglycemia, gastrointestinal side effects, pancreatic safety (pancreatitis and pancreatic cancer), thyroid cancer, gallbladder events, cardiovascular aspects, acute kidney injury, diabetic retinopathy (DRP) complications and injection-site and allergic reactions and where available, we highlight potential underlying mechanisms. Furthermore, we discuss whether effects are specific for semaglutide or a class effect. We conclude that semaglutide induces mostly mild-to-moderate and transient gastrointestinal disturbances and increases the risk of biliary disease (cholelithiasis). No unexpected safety issues have arisen to date, and the established safety profile for semaglutide is similar to that of other GLP-1RAs where definitive conclusions for pancreatic and thyroid cancer cannot be drawn at this point due to low incidence of these conditions. Due to its potent glucose-lowering effect, patients at risk for deterioration of existing DRP should be carefully monitored if treated with semaglutide, particularly if also treated with insulin. Given the beneficial metabolic and cardiovascular actions of semaglutide, and the low risk for severe adverse events, semaglutide has an overall favorable risk/benefit profile for patient with type 2 diabetes.

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Section: Semaglutidementioning

confidence: 99%

Safety of Semaglutide

2021

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“…Among the included studies on subcutaneous semaglutide administration, five trials investigated its efficacy and safety compared to placebo (Marso et al, 2016;Sorli et al, 2017;Rodbard et al, 2018;Zinman et al, 2019b;Davies et al, 2021); nine trials assessed its efficacy and safety versus other antidiabetic drugs, including sitagliptin (Ahrén et al, 2017;Seino et al, 2018;Ji et al, 2020), canagliflozin (Lingvay et al, 2019), dulaglutide (Pratley et al, 2018), liraglutide (Capehorn et al, 2020), exenatide extended-release (Ahmann et al, 2018), insulin glargine (Aroda et al, 2017), and oral antihyperglycemic medications (Kaku et al, 2018). The sample size of these trials ranged from 302 in the SUSTAIN 9 study (Zinman et al, 2019b) to 3,297 in the SUSTAIN 6 study (Marso et al, 2016).…”

Section: Search Results and Included Studiesmentioning

confidence: 99%

Efficacy and Safety of Subcutaneous and Oral Semaglutide Administration in Patients With Type 2 Diabetes: A Meta-Analysis

et al. 2021

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Background: This meta-analysis aimed to combine the data available from clinical trials to assess the effects of subcutaneous and oral semaglutide administration on glycemic control, weight management, and safety outcomes in patients with type 2 diabetes (T2D).Methods: We systematically searched for phase 3 randomized controlled trials (RCTs) that compared semaglutide with placebo or other anti-diabetic drugs in T2D patients. The primary outcome was the change from baseline in glycated hemoglobin (HbA1c) levels. Secondary efficacy endpoints included the change from baseline in body weight, achievement of HbA1c targets, and clinically significant weight loss. Key safety outcomes were also assessed.Results: In this meta-analysis, 24 trials with a total of 22185 patients were included. Subcutaneous semaglutide administration reduced HbA1c levels (weighted mean difference [WMD]: −1.14% and −1.37%, for 0.5 mg and 1 mg, respectively) and body weight (WMD: −2.73 kg and −4.09 kg, for 0.5 mg and 1 mg, respectively) when compared with placebo; its efficacy was also superior to other anti-diabetic drugs in reducing HbA1c levels (WMD: −0.71% and −0.86%, for 0.5 mg and 1 mg, respectively) and body weight (WMD: −2.65 kg and −3.78 kg, for 0.5 mg and 1 mg, respectively). Oral semaglutide administration was superior to placebo in decreasing HbA1c levels (WMD: −0.96% and −1.02%, for 7 mg and 14 mg, respectively). Moreover, oral administration of 14 mg of semaglutide also showed a significant reduction in HbA1c levels (WMD: −0.36%) compared with other anti-diabetic drugs. Furthermore, oral semaglutide administration resulted in substantial weight loss compared with other anti-diabetic drugs (WMD: −1.53 kg and −1.73 kg, for 7 mg and 14 mg, respectively). Notably, subcutaneous and oral semaglutide administration also resulted in higher numbers of patients achieving the targets of HbA1c levels and weight loss than placebo and other anti-diabetic drugs. Overall, we noted no clear evidence of detrimental effects on safety endpoints due to semaglutide treatment, except for some gastrointestinal adverse events.Conclusion: Both subcutaneous and oral semaglutide administration could enable the achievement of sufficient glycemic control and weight management without increasing the risk of hypoglycemia, which were effective and safe for the treatment of T2D.

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“…The participants in these trials were aged between 18 to 70 years old. Among all included studies, ten trials reported changes in BMI and weight [28,29,[35][36][37][38][39][40][41][42], two studies only reported BMI [43,44], and six studies only reported body weight [45][46][47][48][49][50].…”

Section: Resultsmentioning

confidence: 99%

Effects of Sitagliptin as Monotherapy and Add-On to Metformin on Weight Loss among Overweight and Obese Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

et al. 2021

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Background Sitagliptin is known as an antidiabetic agent inhibiting the dipeptidyl peptidase-4. Although sitagliptin may influence weight, controversial results have been reported, and there is no general agreement on this issue. Therefore, this study assessed the effect of sitagliptin as monotherapy and add-on therapy to metformin on weight reduction in overweight or obese cases with type 2 diabetes. Methods We reviewed the following databases to identify all relevant papers published until 1st April 2021: Web of Science, MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials Cochrane Library, and Google Scholar. The research included all clinical trials investigating the effect of sitagliptin in obese or overweight adult patients with type 2 diabetes without any language restriction. Results In total, eighteen randomized controlled trials with 2009 participants were included in our meta-analysis. Results showed supplementation of sitagliptin has led to weight loss for sitagliptin treated (MD −0.99; 95% CI; (−1.87, −0.12); p=0.026)) and sitagliptin+metformin treated groups (MD −1.09; 95% CI; (−1.69, −0.49); p<0.001)). Also, the intervention has influenced body mass index in sitagliptin treated (MD −0.23; 95% CI; (−0.45, 0.02); p=0.033)) and sitagliptin+metformin treated groups (MD −0.52; 95% CI; (−0.96, 0.08); p=0.020)) comparing to placebo. Conclusion Our results demonstrated that sitagliptin administration with or without metformin might reduce the body weight and body mass index if these drugs are taken for more than 6 months.

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Efficacy and safety of once‐weekly semaglutide versus once‐daily sitagliptin as add‐on to metformin in patients with type 2 diabetes in SUSTAIN China: A 30‐week, double‐blind, phase 3a, randomized trial

Cited by 57 publications

References 37 publications

Safety of Semaglutide

Safety of Semaglutide

Efficacy and Safety of Subcutaneous and Oral Semaglutide Administration in Patients With Type 2 Diabetes: A Meta-Analysis

Effects of Sitagliptin as Monotherapy and Add-On to Metformin on Weight Loss among Overweight and Obese Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

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