The efficacy and safety of oral semaglutide for glycaemic management in adults with type 2 diabetes compared to subcutaneous semaglutide, placebo, and other GLP-1 RA comparators: A systematic review and network meta-analysis

Jul 11, 2022Contemporary clinical trials communications

Effectiveness and safety of oral semaglutide for blood sugar control in adults with type 2 diabetes compared to injected semaglutide, placebo, and other similar drugs

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Abstract

Oral semaglutide (14.0 mg) significantly reduced glycated haemoglobin (HbA1c) by 1.30% and body weight by 3.17 kg compared to placebo in a review of 12 studies involving 6840 participants.

Oral semaglutide demonstrated a greater reduction in HbA1c and body weight compared to placebo, liraglutide, exenatide, and dulaglutide.
Compared to subcutaneous semaglutide, oral semaglutide was slightly less effective in reducing HbA1c and body weight.
The incidence of adverse events, including nausea and vomiting, was higher with oral semaglutide compared to placebo and other GLP-1 RAs, but not compared to subcutaneous semaglutide.
Oral semaglutide was found to be non-inferior to subcutaneous semaglutide in efficacy while offering advantages in administration route.

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AIM: Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) indicated for glycaemic management in adults with type 2 diabetes (T2D). Oral semaglutide administration can help decrease glycated haemoglobin (HbA1c) and body weight in people with uncontrolled T2D. We evaluated the efficacy and safety of oral semaglutide compared to that of subcutaneous semaglutide, placebo, and other GLP-1 RAs in the treatment of T2D.

METHODS: Randomised controlled trials of subcutaneous and oral semaglutide for glycaemic control in adults with T2D were selected from the Cochrane Central Register of Controlled Trials and PubMed. Mean differences (MDs) and risk ratios with 95% confidence intervals (CIs) were used to synthesise the results, and oral and subcutaneous semaglutide formulations were indirectly compared using mixed treatment comparisons.

RESULTS: Twelve studies were included in this review (6840 participants). Oral semaglutide (14.0 mg) significantly reduced HbA1c (MD, -1.30% [95%CI: -1.44, -1.16], P < 0.05) and body weight (MD, -3.17 kg [95%CI: -3.89, -2.45], P < 0.05) compared to placebo (MD, HbA1c: -0.32% [95%CI: -0.49, -0.15], P < 0.05; MD body weight: -2.56 kg [95%CI: -3.41, -1.71], P < 0.05), liraglutide (1.2 mg), exenatide ER (2.0 mg), and dulaglutide (1.5 mg). Oral semaglutide was slightly less effective than subcutaneous semaglutide in reducing HbA1c levels (MD: -0.26% [95%CI: -0.44, -0.07], P < 0.05) and body weight (MD: -1.08 kg [95%CI: -2.04, -0.12], P < 0.05). Oral semaglutide increased the incidence of adverse events (nausea, diarrhoea, dyspepsia, and vomiting) compared to placebo, liraglutide (1.2 mg), exenatide (ER, 2.0 mg), and dulaglutide 1.5 mg but not compared to subcutaneous semaglutide.

CONCLUSION: Oral semaglutide was non-inferior to subcutaneous semaglutide and superior to placebo and another GLP-1 RA in reducing HbA1c and body weight. It was superior to subcutaneous semaglutide and inferior to other GLP-1 RA comparators and placebo in terms of the incidence of adverse events. Thus, oral semaglutide provides a convenient administration route for patients who prefer oral treatments over injectable therapies.

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The efficacy and safety of oral semaglutide for glycaemic management in adults with type 2 diabetes compared to subcutaneous semaglutide, placebo, and other GLP-1 RA comparators: A systematic review and network meta-analysis

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