Type 2 diabetes: efficacy and safety of oral semaglutide

  • Avgerinos I & al.
  • Diabetes Obes Metab
  • 21 Oct 2019

  • curated by Sarfaroj Khan
  • UK Clinical Digest
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  • In patients with type 2 diabetes mellitus (T2DM), oral semaglutide can effectively and safely reduce blood glucose level, body weight, and systolic blood pressure (SBP).
  • However, it is associated with an increased risk for gastrointestinal adverse events.

Why this matters

  • Oral semaglutide, a novel once-daily glucagon-like peptide (GLP-1) receptor agonists developed as a tablet, has been recently approved for T2DM.
  • Individual randomised controlled trials (RCTs) have assessed its efficacy in reducing blood glucose and body weight, however, the totality of the evidence base has not been systematically reviewed

Study design

  • 11 randomised controlled trials (RCTs; n=9890) met eligibility criteria after a search across electronic databases.
  • Primary outcome: change in glycated haemoglobin (HbA1c) level from baseline.
  • Funding: None.

Key results

  • Oral semaglutide vs placebo was associated with reduction in:
    • HbA1c level (weighted mean difference [WMD], -0.89%; 95% CI -1.07 to -0.71; I2, 81%)
    • body weight (WMD, -2.99 kg; 95% CI -3.69 to -2.30; I2, 78%),
    • all-cause (OR, 0.58; 95% CI, 0.37-0.92) and cardiovascular (OR, 0.55; 95% CI, 0.31-0.98) mortality.
  • Semaglutide was also superior than other active comparators (including liraglutide, empagliflozin and sitaglipitin) in lowering HbA1c level (WMD, -0.35%; 95% CI, -0.43 to −0.26) and body weight (WMD, -1.48 kg; 95% CI, −2.28 to −0.67; I2, 82%).
  • Semaglutide showed reduction in SBP vs placebo (WMD, -3.16 mmHg; 95% CI, -4.56 to −1.77; I2, 52%) and other antidiabetic agents (WMD, -1.46 mmHg; 95% CI, -2.53 to -0.40).
  • Semaglutide did not increase the risk for myocardial infarction, stroke, severe hypoglycaemia, and diabetic retinopathy.
  • Incidence of nausea, vomiting, and diarrhoea increased with semaglutide vs placebo or other antidiabetic agents and events of acute pancreatitis were infrequent across all groups.


  • High level of heterogeneity.