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Oral Semaglutide Shows Promise in HbA1c Reduction and Weight Loss

Nov 3, 2018
Editor: Joy Pape, MSN, FNP-C, CDE, WOCN, CFCN, FAADE

Author: Angela Reyes, Pharm.D. Candidate, LECOM College of Pharmacy

First oral GLP-1 agonist undergoing Phase 3 trials shows significant benefits managing type 2 diabetes.

GLP-1 agonists help increase insulin secretion from beta cells and suppress glucagon secretion from alpha-cells. An added benefit of these antidiabetes medications is that they slow gastric emptying and promote satiety. The newest addition to this drug class is called semaglutide. This GLP-1 agonist has shown to have greater weight reduction than liraglutide in a head-to-head study. It is also the only GLP-1 agonist with oral tablet administration available. In the PIONEER 1 Trial, oral semaglutide was researched for its effectiveness and safety.

In a randomized double-blind, placebo-controlled phase 3a trial, oral semaglutide was administered once daily to drug-naïve patients with type 2 diabetes. There were 703 participants enrolled. They all had consistently high blood glucose. The trial duration was 23 weeks and primary outcome was change in HbA1c. Groups received either 3, 7, or 14mg of semaglutide or a placebo once daily. Baseline characteristics were generally equal with 49% of participants female, mean age of 55, and mean duration of diabetes of 3.5 years.

Results showed reduction in HbA1c and weight at all doses of semaglutide. In the 3 mg group, an HbA1c reduction of 0.9% was seen. In the 7 mg and 14 mg groups, a reduction of 1.2% and 1.4%, respectively, was seen. The placebo group had a 0.3% reduction in HbA1c.

Weight reductions from baseline were 1.5% with the 3 mg dose, 2.3% with the 7 mg dose, and 3.7% with the 14 mg dose. In the highest dosage group (14 mg) a mean weight loss of 4.3 kg was observed by the end of the study. Weight loss on placebo was 1.4%. Adverse events occurred in 58% of patients on the 3 mg dose, 53% on the 7 mg dose, and 57% on the 14 mg dose. The placebo group had a similar rate of adverse events at 56%. The most reported adverse event was nausea in all groups, including placebo.

Oral semaglutide showed superiority over placebo in reducing HbA1c and weight. It also proved to be well tolerated in patients with type 2 diabetes who had consistently high blood glucose. Metformin is the standard first line treatment for type 2 diabetes. This trial showed such a significant reduction in HbA1c (especially at 14 mg), weight reduction, and tolerability that using it earlier on in patient diagnosis may be beneficial. A trial comparing it head-to-head with metformin would be ideal. When injectable semaglutide was recently compared to liraglutide, its efficacy dominated over the other GLP-1 agonist. With an oral option of semaglutide available, it could easily become the drug of choice for managing type 2 diabetes.

Practice Pearls:

  • GLP-1 agonists reduce weight and HbA1c and generally are well tolerated. Oral semaglutide is still in phase 3 trials but would be the first non-injectable in its class.
  • Compared with placebo, people with type 2 diabetes who had consistently high blood glucose had significant reductions in HbA1c and weight loss.
  • Oral daily doses of semaglutide had no significant difference in adverse events than placebo.


Vanita R. Aroda, Julio Rosenstock, Yasuo Terauchi, Ole Jeppesen, Erik Christiansen, Christin L. Hertz and Martin Haluzik. Effect and Safety of Oral Semaglutide Monotherapy in Type 2 Diabetes, PIONEER 1 Trial. Diabetes (2018)67:Supp1. https://doi.org/10.2337/db18-2-LB

The Lancet. 392 Issue 10148 (August 2018): 637-649. https://doi.org/10.1016/S0140-6736(18)31773-2

Angela Reyes, Pharm.D. Candidate, LECOM College of Pharmacy