Efficacy of Oral and Subcutaneous Semaglutide in T2D

Doctor holding a pill
Doctor holding a pill
All dosages of oral semaglutide reduced mean HbA1c level significantly more than placebo by week 26.

The use of oral and subcutaneous semaglutide may provide better glycemic control than placebo in patients with type 2 diabetes (T2D), according to a study published in the Journal of the American Medical Association

Researchers conducted a phase 2, randomized parallel-group, dosage-finding 26-week trial (ClinicalTrials.gov identifier: NCT01923181) with 5 weeks of follow-up at 100 sites in 14 different countries between December 2013 and December 2014. The study consisted of of 1106 participants, including 632 participants with a diagnosis of T2D who had insufficient glycemic control on diet and activity alone or a stable dose of metformin. The change in hemoglobin A1C (HbA1C) from baseline to week 26 was the primary end point studied.

Participants were randomly assigned to receive either 2.5-mg, 5-mg, 10-mg, 20-mg, or 40-mg 4-week dose escalation; 40-mg 8-week dose escalation; 40-mg 2-week dose escalation; oral placebo; or once-weekly subcutaneous semaglutide of 1.0 mg for 26 weeks (n=70, 70, 70, 70, 71, 70, 70, 71, 70, respectively). No differences in baseline characteristics were identified.

Study results demonstrated a dose-dependent mean change in HbA1C in patients treated with oral semaglutide, subcutaneous semaglutide, and placebo (-0.7% to -1.9%, -1.9%, -0.3%, respectively). Reductions with oral semaglutide were significant compared with placebo (dose-dependent estimated treatment difference range for oral semaglutide vs placebo, -0.4% to -1.6%; P =.01 for 2.5 mg, P <.001 for all other dosages). Nearly 100% of patients treated with either oral or subcutaneous semaglutide demonstrated a reduction in HbA1C, with the exception of those treated with the 2.5-mg dose. In addition, significant weight reductions were noted in those treated with oral semaglutide (dose-dependent range, -2.1 kg to -6.9 kg), and subcutaneous semaglutide (-6.4 kg), compared with placebo (-1.2 kg).

Related Articles

“Among patients with type 2 diabetes, oral semaglutide resulted in better glycemic control than placebo over 26 weeks,” concluded the investigators. Clinicians should consider the use of an oral semaglutide to treat people with T2D who are unable to achieve glycemic control with diet and exercise alone. 

Study findings support a phase 3 trial to determine long-term outcomes and safety of oral semaglutide use in patients with T2D.


Davies M, Pieber TR, Hartoft-Nielsen ML, Hansen OKH, Jabbour S, Rosenstock J.  Effect of oral semaglutide compared with placebo and subcutaneous semaglutide on glycemic control in patients with type 2 diabetes: a randomized clinical trial. JAMA. 2017;318:1460-1470.