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

Abstract

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.

Side effect profile of pharmacologic therapies for liver fibrosis in nonalcoholic fatty liver disease: a systematic review and network meta-analysis

“…Liraglutide was related to higher occurrences of constipation than aramchol, lanifibranor, placebo and selonsertib. For patients with type 2 diabetes (T2D), several meta-analyses found that compared with other therapies or placebo, using semaglutide resulted in an increase in gastrointestinal adverse events [79][80][81]. This was consistent with our findings that diarrhea was more common when using semaglutide compared with cenicriviroc, obeticholic acid, placebo and selonsertib.…”

Efficacy and safety of semaglutide on weight loss in obese or overweight patients without diabetes: A systematic review and meta-analysis of randomized controlled trials

“…At present, semaglutide is mainly available in two formulations, once-weekly subcutaneous semaglutide (Ozempic ® , 0.5 mg or 1.0 mg; Wegovy ® , 2.4 mg) and once-daily oral semaglutide (Rybelsus ® , 7 mg or 14 mg) ( Meier 2021 ; Zhong et al, 2021 ), the first oral GLP-1RA in the world, which provides effective glycemic control in type 2 diabetes when combined with diet and exercise intervention, bringing great convenience to patients ( Davies et al, 2017 ; Gibbons et al, 2021 ). We hope that more clinical trials will be conducted in the future to evaluate the weight loss effects of oral semaglutide so as to provide a more convenient, effective, and safe treatment for the majority of obese patients.…”

Efficacy and safety of tirzepatide in patients with type 2 diabetes: A systematic review and meta-analysis

“…As for semaglutide administered in patients with T2D, compared with placebo, subcutaneous semaglutide led to body weight loss (WMD: -2.73 kg and -4.09 kg, for 0.5 mg and 1 mg, respectively). Oral administration showed similar effects ( Zhong et al, 2021 ). For treatment with dulaglutide in patients with T2D, the mean weight loss was 0.73 kg in the 0.75 mg dulaglutide group and 1.27 kg in the 1.5 mg dulaglutide group ( Qie et al, 2020 ).…”