Oral "ozempic" lowers A1c and body weight in patients with type 2 diabetes

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.

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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 (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.

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.