PIONEER 1 was a 26-week randomized clinical trial conducted in nine countries. It tested the efficacy and safety of oral semaglutide vs. placebo in diabetes patients with baseline A1c 8.0%. A group of 703 adults was monitored and analyzed.

At 24 weeks, the higher dose 14 mg of oral semaglutide reduced A1c and body weight by about 1.2% and 5 lbs respectively. Results were statistically significant. Gastrointestinal side effects were more common with semaglutide than placebo but similar to other GLP-1 agonists in the market.

The above results are promising for oral semaglutide to receive FDA approval.

Also see:

GLP-1 agonist

Diabetes

Obesity

Diabetes Care

PIONEER 1

July 2019

OBJECTIVE

This trial compared the efficacy and safety of the first oral glucagon-like peptide 1 receptor agonist, oral semaglutide, as monotherapy with placebo in patients with type 2 diabetes managed by diet and exercise alone.

Two estimands (parameters) addressed two efficacy-related questions:

Treatment policy estimand, −0.6% [3 mg], −0.9% [7 mg], and −1.1% [14 mg]
Trial product estimand, −0.7% [3 mg], −1.2% [7 mg], and −1.4% [14 mg]; (P < 0.001 for all)
Body weight (treatment policy, −0.1 kg [3 mg], −0.9 kg [7 mg], and −2.3 kg [14 mg] (P < 0.001);
Trial product, −0.2 kg [3 mg], −1.0 kg [7 mg, P = 0.01], and −2.6 kg [14 mg, P < 0.001]).
Mild-to-moderate transient gastrointestinal events were the most common adverse events with oral semaglutide.
Trial product discontinuations occurred in 2.3–7.4% with oral semaglutide and 2.2% with placebo.

CONCLUSIONS

In patients with type 2 diabetes, oral semaglutide monotherapy demonstrated superior and clinically relevant improvements in HbA1c (all doses) and body weight loss (14 mg dose) versus placebo, with a safety profile consistent with other GLP-1 receptor agonists.

Primary endpoint was change from baseline to week 26 in HbA1c.
Confirmatory secondary endpoint was change from baseline to week 26 in body weight.

RESULTS

In the 703 patients randomized (mean age 55 years, 50.8% male, and mean baseline HbA1c 8.0%, oral semaglutide reduced HbA1c (placebo-adjusted treatment differences at week 26:

Treatment policy estimand, −0.6% [3 mg], −0.9% [7 mg], and −1.1% [14 mg]
Trial product estimand, −0.7% [3 mg], −1.2% [7 mg], and −1.4% [14 mg]; (P < 0.001 for all)
Body weight (treatment policy, −0.1 kg [3 mg], −0.9 kg [7 mg], and −2.3 kg [14 mg] (P < 0.001);
Trial product, −0.2 kg [3 mg], −1.0 kg [7 mg, P = 0.01], and −2.6 kg [14 mg, P < 0.001]).
Mild-to-moderate transient gastrointestinal events were the most common adverse events with oral semaglutide.
Trial product discontinuations occurred in 2.3–7.4% with oral semaglutide and 2.2% with placebo.

CONCLUSIONS

Treatment policy estimand (regardless of trial product discontinuation or rescue medication use) and a
Trial product estimand (on trial product without rescue medication use) in all randomized patients.

RESEARCH

This was a 26-week, phase 3a, randomized, double-blind, placebo-controlled, parallel-group trial conducted in 93 sites in nine countries.

Adults with type 2 diabetes insufficiently controlled with diet and exercise were randomized (1:1:1:1) to once-daily oral semaglutide 3 mg, 7 mg, 14 mg, or placebo.

Primary endpoint was change from baseline to week 26 in HbA1c.
Confirmatory secondary endpoint was change from baseline to week 26 in body weight.

RESULTS

In the 703 patients randomized (mean age 55 years, 50.8% male, and mean baseline HbA1c 8.0%, oral semaglutide reduced HbA1c (placebo-adjusted treatment differences at week 26:

Treatment policy estimand, −0.6% [3 mg], −0.9% [7 mg], and −1.1% [14 mg]
Trial product estimand, −0.7% [3 mg], −1.2% [7 mg], and −1.4% [14 mg]; (P < 0.001 for all)
Body weight (treatment policy, −0.1 kg [3 mg], −0.9 kg [7 mg], and −2.3 kg [14 mg] (P < 0.001);
Trial product, −0.2 kg [3 mg], −1.0 kg [7 mg, P = 0.01], and −2.6 kg [14 mg, P < 0.001]).
Mild-to-moderate transient gastrointestinal events were the most common adverse events with oral semaglutide.
Trial product discontinuations occurred in 2.3–7.4% with oral semaglutide and 2.2% with placebo.