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PIONEER 3: Oral semaglutide bests sitagliptin for HbA1c reduction

NEW ORLEANS — Oral semaglutide, as an add-on to metformin with or without a sulfonylurea, resulted in greater HbA1c reductions after 26 weeks compared with sitagliptin, according to new data from the PIONEER 3 trial.

The mean change in HbA1c from baseline to 26 weeks — the primary endpoint — was –0.6% with semaglutide 3 mg per day, –1% with semaglutide 7 mg per day and –1.3% with semaglutide 15 mg per day compared with –0.8% with sitagliptin (Januvia, Merck) 100 mg per day. The 7-mg and 14-mg daily doses of semaglutide were superior to sitagliptin for reducing HbA1c from baseline to week 26, resulting in an estimated treatment difference of –0.3% and –0.5%, respectively (P < .001 for both).

Noninferiority of the 3-mg semaglutide dose, compared with sitagliptin, was not demonstrated.

Change in body weight over 26 weeks — a key secondary endpoint — was reduced by –1.6 kg with 7-mg semaglutide and –2.5 kg with 14-mg semaglutide compared with sitagliptin (P < .001 for both).

The data were presented as a poster and simultaneously published in JAMA.

In total, 2,463 patients were screened for the randomized, double-blind, phase 3 trial. Of those, 1,864 had type 2 diabetes uncontrolled with metformin, with or without a sulfonylurea, and were randomly assigned to once-daily oral semaglutide 3 mg, 7 mg or 14 mg, or sitagliptin 100 mg. Semaglutide was started at 3 mg per day and then escalated every 4 weeks in ascending doses until the randomized dosage was achieved.

“The doses of oral semaglutide used in this trial are greater than the largest dose of subcutaneous semaglutide assessed in the SUSTAIN program,” the researchers wrote in JAMA.

At baseline, the mean age of the patients was 58 years, mean baseline HbA1c was 8.3%, mean BMI was 32.5 kg/m2 and 47% were women. Mean duration of diabetes was 8.6 years. Fasting plasma glucose was 171 mg/dL. All patients were taking background metformin; approximately half in each treatment group were also receiving sulfonylurea.

The randomized, double-blind, phase 3 trial was conducted at 206 sites in 14 countries for 78 weeks.

In other results, from baseline to 78 weeks, reductions in HbA1c were significantly greater with semaglutide 7 mg and 14 mg, and body weight reductions were significantly greater with all dosages of semaglutide, compared with sitagliptin.

The proportion of patients experiencing at least one adverse event during treatment was similar across all treatment groups. The most frequent adverse events were gastrointestinal (GI) disorders in the 14-mg semaglutide group and infections and infestations in the 3-mg and 7-mg semaglutide and sitagliptin groups. GI adverse events were mostly mild or moderate, with nausea the most common GI event in the 7-mg and 14-mg semaglutide groups. “The long-term adverse events profile of oral semaglutide in this trial was consistent with the GLP-1 receptor agonist class as a whole,” the researchers wrote in JAMA.

Premature discontinuation occurred in 16.7% of the 3-mg semaglutide group, 15% of the 7-mg group and 19.1% of the 14-mg group vs. 13.1% of the sitagliptin group.

The PIONEER 3 results are “consistent with other head-to-head trials that have demonstrated superior glycemic control and weight reduction with GLP-1 receptor agonists over DPP-IV inhibitors,” the researchers wrote in JAMA.

As previously reported by Endocrine Today, Novo Nordisk on March 20 submitted two new drug applications for oral semaglutide, seeking approval for the drug as an adjunct to diet and exercise in adults with type 2 diabetes along with an indication to reduce the risk for major adverse cardiovascular events in patients with established CV disease. – by Katie Kalvaitis

References:

Rosenstock J, et al. SAT-139. Clinical impact of oral semaglutide compared with sitagliptin in T2D on metformin ± sulfonylurea: The Pioneer 3 trial. Presented at: The Endocrine Society Annual Meeting; March 23-26, 2019; New Orleans.

Rosenstock J, et al. JAMA. 2019;doi:10.1001/jama.2019.2942.

Disclosures: This trial was funded by Novo Nordisk. Rosenstock reports he is an advisory board member and consultant for Boehringer Ingelheim, Eli Lilly and Company, Intarcia, Janssen, Novo Nordisk and Sanofi and has received grants from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company, Genentech, GlaxoSmithKline, Intarcia, Janssen, Lexicon Pharmaceuticals, Merck, Novo Nordisk, Pfizer and Sanofi. Please see the study for all other authors’ relevant financial disclosures.

NEW ORLEANS — Oral semaglutide, as an add-on to metformin with or without a sulfonylurea, resulted in greater HbA1c reductions after 26 weeks compared with sitagliptin, according to new data from the PIONEER 3 trial.

The mean change in HbA1c from baseline to 26 weeks — the primary endpoint — was –0.6% with semaglutide 3 mg per day, –1% with semaglutide 7 mg per day and –1.3% with semaglutide 15 mg per day compared with –0.8% with sitagliptin (Januvia, Merck) 100 mg per day. The 7-mg and 14-mg daily doses of semaglutide were superior to sitagliptin for reducing HbA1c from baseline to week 26, resulting in an estimated treatment difference of –0.3% and –0.5%, respectively (P < .001 for both).

Noninferiority of the 3-mg semaglutide dose, compared with sitagliptin, was not demonstrated.

Change in body weight over 26 weeks — a key secondary endpoint — was reduced by –1.6 kg with 7-mg semaglutide and –2.5 kg with 14-mg semaglutide compared with sitagliptin (P < .001 for both).

The data were presented as a poster and simultaneously published in JAMA.

In total, 2,463 patients were screened for the randomized, double-blind, phase 3 trial. Of those, 1,864 had type 2 diabetes uncontrolled with metformin, with or without a sulfonylurea, and were randomly assigned to once-daily oral semaglutide 3 mg, 7 mg or 14 mg, or sitagliptin 100 mg. Semaglutide was started at 3 mg per day and then escalated every 4 weeks in ascending doses until the randomized dosage was achieved.

“The doses of oral semaglutide used in this trial are greater than the largest dose of subcutaneous semaglutide assessed in the SUSTAIN program,” the researchers wrote in JAMA.

At baseline, the mean age of the patients was 58 years, mean baseline HbA1c was 8.3%, mean BMI was 32.5 kg/m2 and 47% were women. Mean duration of diabetes was 8.6 years. Fasting plasma glucose was 171 mg/dL. All patients were taking background metformin; approximately half in each treatment group were also receiving sulfonylurea.

The randomized, double-blind, phase 3 trial was conducted at 206 sites in 14 countries for 78 weeks.

In other results, from baseline to 78 weeks, reductions in HbA1c were significantly greater with semaglutide 7 mg and 14 mg, and body weight reductions were significantly greater with all dosages of semaglutide, compared with sitagliptin.

The proportion of patients experiencing at least one adverse event during treatment was similar across all treatment groups. The most frequent adverse events were gastrointestinal (GI) disorders in the 14-mg semaglutide group and infections and infestations in the 3-mg and 7-mg semaglutide and sitagliptin groups. GI adverse events were mostly mild or moderate, with nausea the most common GI event in the 7-mg and 14-mg semaglutide groups. “The long-term adverse events profile of oral semaglutide in this trial was consistent with the GLP-1 receptor agonist class as a whole,” the researchers wrote in JAMA.

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Premature discontinuation occurred in 16.7% of the 3-mg semaglutide group, 15% of the 7-mg group and 19.1% of the 14-mg group vs. 13.1% of the sitagliptin group.

The PIONEER 3 results are “consistent with other head-to-head trials that have demonstrated superior glycemic control and weight reduction with GLP-1 receptor agonists over DPP-IV inhibitors,” the researchers wrote in JAMA.

As previously reported by Endocrine Today, Novo Nordisk on March 20 submitted two new drug applications for oral semaglutide, seeking approval for the drug as an adjunct to diet and exercise in adults with type 2 diabetes along with an indication to reduce the risk for major adverse cardiovascular events in patients with established CV disease. – by Katie Kalvaitis

References:

Rosenstock J, et al. SAT-139. Clinical impact of oral semaglutide compared with sitagliptin in T2D on metformin ± sulfonylurea: The Pioneer 3 trial. Presented at: The Endocrine Society Annual Meeting; March 23-26, 2019; New Orleans.

Rosenstock J, et al. JAMA. 2019;doi:10.1001/jama.2019.2942.

Disclosures: This trial was funded by Novo Nordisk. Rosenstock reports he is an advisory board member and consultant for Boehringer Ingelheim, Eli Lilly and Company, Intarcia, Janssen, Novo Nordisk and Sanofi and has received grants from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company, Genentech, GlaxoSmithKline, Intarcia, Janssen, Lexicon Pharmaceuticals, Merck, Novo Nordisk, Pfizer and Sanofi. Please see the study for all other authors’ relevant financial disclosures.

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