Oral semaglutide for type 2 diabetes: a systematic review and meta-analysis.

To assess the efficacy and safety of oral semaglutide, a novel glucagon-like peptide 1 receptor agonist, for patients with type 2 diabetes mellitus.

We searched Medline, Embase, the Cochrane Library, and grey literature sources up to July 1^st 2019 for randomized controlled trials (RCTs) comparing oral semaglutide with placebo or other antidiabetic agents. The primary outcome was change from baseline in glycated hemoglobin (HbA_1c ). Secondary outcomes included change from baseline in body weight and blood pressure, cardiovascular endpoints, severe hypoglycemia, gastrointestinal adverse events and diabetic retinopathy. We synthesized results using weighted mean differences (WMDs) for continuous outcomes, and odds ratios (ORs) for dichotomous outcomes, along with 95% confidence intervals (CIs).

We included 11 RCTs with 9890 patients in the systematic review. Compared with placebo, oral semaglutide reduced HbA_1c and body weight (WMD -0.89%, 95% CI -1.07 to -0.71 and -2.99 kg, 95% CI -3.69 to -2.30 respectively). Oral semaglutide was also superior to other active comparators (including liraglutide, empagliflozin and sitaglipitin) in terms of HbA_1c lowering (WMD -0.35%, 95% CI -0.43 to -0.26) and reduction of body weight (WMD -1.48 kg, 95% CI -2.28 to -0.67), and had a favorable effect on systolic blood pressure. Compared with placebo, oral semaglutide reduced all-cause mortality (OR 0.58, 95% CI 0.37 to 0.92) and cardiovascular mortality (OR 0.55, 95% CI 0.31 to 0.98), and had a neutral effect on myocardial infarction, stroke, severe hypoglycemia and diabetic retinopathy. However, treatment with oral semaglutide increased the incidence of nausea, vomiting and diarrhea, while events of acute pancreatitis were rare.

Oral semaglutide can effectively and safely reduce blood glucose, body weight and systolic blood pressure. Nevertheless, it is associated with increased incidence of gastrointestinal adverse events. Further research is needed to clarify its long-term safety and comparative effectiveness against other antidiabetic agents. This article is protected by copyright. All rights reserved.