Semaglutide Consistently Reduces Both Fasting and Postprandial Glucose Levels Across Sustain 1–5 Clinical Trials

Presentation Number: SUN 622
Date of Presentation: April 2nd, 2017

Vanita R. Aroda*1, Jeffrey Unger2, Bertrand Cariou3, Sune Birch4, Sayeh Tadayon4 and Esteban Jódar5
1Medstar Health Research Institute, Hyattsville, MD, 2Catalina Research Institute, Chino, CA, 3L’institut du thorax, CHU Nantes, INSERM, CNRS, Université de Nantes, Nantes, FRANCE, 4Novo Nordisk A/S, Søborg, Denmark, 5Hospital Universitario Quirón Salud Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid, Spain

Abstract

Background

Improvements in fasting plasma glucose (FPG) and postprandial glucose (PPG) levels are major contributors to achieving HbA1c targets in subjects with type 2 diabetes (T2D).1,2 Short-acting glucagon-like peptide-1 receptor agonists (GLP-1 RAs) generally demonstrate greater improvements in PPG following injection, while long-acting GLP-1 RAs show a greater effect on FPG and more modest effects on PPG.3 Semaglutide is a GLP‑1 analog in development for the once-weekly treatment of T2D. Semaglutide has demonstrated superior HbA1creductions (1.2–1.5% with semaglutide 0.5 mg and 1.5–1.8% with semaglutide 1.0 mg), vs comparators, across the phase 3a SUSTAIN 1–5 clinical trials, when used as monotherapy, add-on to metformin, 1–2 oral anti-diabetic medications, or with basal insulin.

Aim

To assess the effect of once-weekly semaglutide subcutaneous on FPG and PPG across the SUSTAIN 1–5 trials.

Methods

In SUSTAIN 1–5, a total of 3918 subjects (HbA1c 7.0–10.0/10.5%) with T2D were randomized to semaglutide 0.5 mg, 1.0 mg, or placebo (SUSTAIN 1); sitagliptin (SUSTAIN 2); exenatide extended release [ER] (SUSTAIN 3, vs semaglutide 1.0 mg only); insulin glargine [IGlar] (SUSTAIN 4); or placebo as add-on to basal insulin (SUSTAIN 5); for 30 or 56 weeks. The effect of semaglutide 0.5 mg and 1.0 mg vs comparators on FPG, and PPG (mean and postprandial increments) from 7/8-point self-measured plasma glucose (SMPG) profile, was assessed (vs baseline) at the end of treatment.

Results

Semaglutide reduced mean FPG (mg/dL) from baseline. Reductions in FPG were significantly greater for semaglutide 1.0 mg vs comparators (estimated treatment difference [ETD]1.0 mg –26.74 vs sitagliptin, –14.93 vs exenatide ER, –10.96 vs IGlar, and –32.55 to –32.76 vs placebo; all p<0.0002). Reductions were also significantly greater for semaglutide 0.5 mg vs sitagliptin and placebo (ETD0.5 mg –17.40, and –20.51 to –34.41, respectively, all p≤0.0002).

Semaglutide reduced mean PPG (mg/dL) increments. The reductions in PPG increments were significantly greater for semaglutide 1.0 mg vs comparators (ETD1.0 mg –6.87 vs sitagliptin, –4.31 vs exenatide ER, –11.76 vs IGlar, and –13.40 to –17.84 vs placebo; all p<0.02). Reductions were also significantly greater for semaglutide 0.5 mg vs IGlar and placebo when added to insulin (ETD0.5 mg –7.09 and –11.57, respectively; both p<0.004) but not vs placebo (monotherapy) and sitagliptin (ETD0.5 mg–7.65 and –3.26, respectively; p=0.0688 and p=0.0926). Mean SMPG levels were significantly reduced with semaglutide 0.5 mg and 1.0 mg vs all comparators (p<0.0001), with the exception of semaglutide 0.5 mg vs IGlar.

Conclusions

Semaglutide consistently reduced FPG and PPG across the SUSTAIN 1–5 clinical trials, suggesting that both components contribute to significantly better glycemic control versus comparators.

 

Disclosure: VRA: Investigator, Astra Zeneca/BMS, Investigator, Calibra, Investigator, Eisai, Investigator, Elcelyx, Investigator, Jansen Pharmaceuticals, Investigator, Novo Nordisk, Investigator, Sanofi, Investigator, Theracos, Consultant, Astra Zeneca, Consultant, Jansen Pharmaceuticals, Consultant, Medscape, Consultant, Novo Nordisk, Consultant, Sanofi, Consultant, Tufts. JU: Speaker Bureau Member, Jansen Pharmaceuticals, Stock owner, Novo Nordisk, Speaker Bureau Member, Novo Nordisk, Advisory Group Member, Novo Nordisk. BC: Consultant, Sanofi, Consultant, Novo Nordisk, Consultant, Merck & Co., Consultant, Jansen Pharmaceuticals, Consultant, Pierre Fabre, Consultant, Astra Zeneca, Consultant, Amgen, Investigator, Pfizer, Inc., Consultant, Regeneron, Investigator, Regeneron, Consultant, Sanofi, Investigator, Sanofi, Consultant, Takeda, Consultant, Eli Lilly & Company. SB: Employee, Novo Nordisk. ST: Employee, Novo Nordisk. EJ: Investigator, Lilly USA, LLC, Consultant, Jansen Pharmaceuticals, Investigator, Jansen Pharmaceuticals, Speaker, MSD, Investigator, MSD, Investigator, GlaxoSmithKline, Speaker, Astra Zeneca, Consultant, Astra Zeneca, Investigator, Astra Zeneca, Speaker, Novo Nordisk, Consultant, Novo Nordisk, Investigator, Novo Nordisk, Consultant, Lilly USA, LLC, Speaker, Lilly USA, LLC.