Physicians' Academy for Cardiovascular Education

Two studies show that oral GLP-1RA can improve glycemic control in uncontrolled T2DM

Literature - Rodbard et al. and Zinman et al. - Diabetes Care 2019 Sep; dc190898.

Oral Semaglutide versus Empagliflozin in Patients with Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial

Rodbard HW, Rosenstock J, Canani LH et al.,

Diabetes Care 2019 Sep; dc190883.

Efficacy, Safety and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin ± Metformin in Patients with Type 2 Diabetes: the PIONEER 8 Trial

Zinman B, Aroda VR, Buse JB et al.,

Diabetes Care 2019 Sep; dc190898.

Introduction and methods

For many patients with type 2 diabetes (T2DM), metformin monotherapy is not sufficient to maintain adequate glycemic control. Injectable GLP-1 receptor agonists (GLP-1RAs) and oral SGLT2 inhibitors (SGLT2i) are now recommended as second-line therapy because they can lower glucose levels without increasing hypoglycemia risk, induce weight loss and are associated with CV benefits [1,2].

Semaglutide is a human GLP-1 analogue that is already available as a once-weekly injection, which is associated with reduced HbA1c, weight loss and fewer CV events in T2DM [3-9]. An oral version has also been developed, optimized to facilitate absorption across the gastric mucosa. This oral semaglutide was shown to give significantly greater reductions in HbA1c and body weight compared with placebo in patients with T2DM uncontrolled with diet and exercise or oral antidiabetic medication, including patients with moderate renal impairment [11-14]. CV safety of oral semaglutide has been confirmed [15].

Two studies evaluating oral semaglutide have recently been published in Diabetes Care.

Key endpoints of both studies were change in %HbA1c from week 1 to week 26, and change in body weight. Both studies used two estimands to address two aspects of the efficacy objective:

Main results

PIONEER 2 | Oral semaglutide vs. empagliflozin, on top of metformin monotherapy

PIONEER 8 | Oral semaglutide vs. placebo, on top of insulin with or without metformin


The PIONEER 2 data show that oral semaglutide, the first oral GLP-1RA to be studied for treatment of T2DM, was superior to the SGLT2i empagliflozin in the reduction of HbA1c at 26 and 52 weeks in patients with T2DM uncontrolled on metformin monotherapy. This comparison did not show superiority of semaglutide with regard to body weight reduction at week 26.

PIONEER 8 showed dose-dependent and statistically significant reductions in HbA1c and body weight compared with placebo over 52 weeks in patients uncontrolled on with insulin with or without metformin. Semaglutide 7 and 14 mg also showed better glycemic control than placebo at weeks 26, despite lower total daily insulin dosage.

Both trials showed a safety profile consistent with earlier studies and with that of other GLP-1RAs.


Show references

Find the article by Rodbard et al. at Diabetes Care Find the article by Zinman et al. at Diabetes Care

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