Semaglutide Reduces HbA1c and Body Weight Across Multiple Background OAD Treatment Categories

Presentation Number: SUN 620
Date of Presentation: April 2nd, 2017

Vanita R. Aroda*1, Juan Pablo Frías2, Ömür Tabak3, Sayeh Tadayon4, Jeppe Zacho4 and Matthew Capehorn5
1Medstar Health Research Institute, Hyattsville, MD, 2National Research Institute, Los Angeles, CA, 3Istanbul Kanuni Sultan Suleyman Education and Research Hospital, Istanbul, Turkey, 4Novo Nordisk A/S, Søborg, Denmark, 5Rotherham Institute for Obesity, Clifton Medical Centre, Rotherham, United Kingdom



Recommended HbA1c targets can be a challenge to achieve for many patients with type 2 diabetes (T2D) despite treatment with oral antidiabetic agents (OADs). Semaglutide, a GLP-1 analog in development for the treatment of T2D, demonstrated superior reductions in HbA1c and body weight (BW) vs comparators in the phase 3a SUSTAIN 1–5 clinical trials. Semaglutide was tested in combination with 1–2 OADs across SUSTAIN 2–4.


This post-hoc analysis evaluated the efficacy and safety of semaglutide across background OAD treatments in SUSTAIN 2–4.


Overall, 3,125 subjects with T2D (HbA1c 7.0–10.0/10.5%) were stratified by background OAD treatment across SUSTAIN 2 (background: metformin [MET], thiazolidinediones [TZD] or MET + TZD; trial products: semaglutide 0.5 mg, 1.0 mg vs sitagliptin 100 mg; treatment duration: 56 weeks), SUSTAIN 3 (background: 1–2 OADs, MET, TZD, sulfonylurea [SU]; trial products: semaglutide 1.0 mg vs exenatide extended release [ER] 2.0 mg; treatment duration: 56 weeks), and SUSTAIN 4 (background: MET or MET + SU; trial products: semaglutide 0.5 mg, 1.0 mg vs insulin glargine [IGlar]; treatment duration: 30 weeks). The following background therapy groups were defined for analysis: MET; MET + SU; or TZD and/or MET or SU (other OADs).


In subjects on MET, both doses of semaglutide significantly reduced HbA1c vs comparators (estimated treatment difference for semaglutide 0.5 mg [ETD0.5 mg], –0.79% vs sitagliptin and –0.45% vs IGlar; ETD semaglutide 1.0 mg vs comparator [ETD1.0 mg], –1.07% vs sitagliptin, –0.37% vs exenatide ER and –0.89% vs IGlar; all p<0.05). In subjects on MET + SU both doses of semaglutide significantly reduced HbA1c vs comparators (ETD0.5 mg –0.31% vs IGlar; ETD1.0 mg –0.90% vs exenatide ER and –0.77% vs IGlar; all p<0.05). In subjects on other OADs, HbA1c was significantly reduced with semaglutide 1.0 mg vs sitagliptin (ETD1.0 mg –0.95%, p<0.05), and reduced with semaglutide 0.5 mg vs sitagliptin (ETD0.5 mg –0.59%) and semaglutide 1.0 mg vs exenatide ER (ETD1.0 mg –0.47%), although significance was not reached.

In all OAD subgroups mean BW reduction was significantly greater with semaglutide 1.0 mg vs sitagliptin, exenatide ER and IGlar (p<0.05). In MET and MET + SU-treated subjects, mean BW reduction with semaglutide 0.5 mg was significantly greater vs comparators (all p<0.0001); the reduction in the other OAD group did not reach statistical significance.

The rate of severe or blood glucose-confirmed symptomatic hypoglycemia with both semaglutide doses was comparable to, or lower than, comparators irrespective of background OAD treatment.


Semaglutide administered subcutaneously, once-weekly, consistently improved HbA1c and reduced BW, vs comparators, in subjects with T2D with a low rate of hypoglycemia, regardless of background OAD treatments investigated in these studies.


Disclosure: VRA: 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, Consultant, Adocia, Investigator, Eisai, Investigator, Calibra, Investigator, Astra Zeneca/BMS, Consultant, ADA. JPF: Principal Investigator, Novo Nordisk. ST: Employee, Novo Nordisk. JZ: Employee, Novo Nordisk, Employee, Novo Nordisk. MC: Consultant, Lighter Life, Speaker, Jansen Pharmaceuticals, Advisory Group Member, Jansen Pharmaceuticals, Speaker, BI/Lilly, Advisory Group Member, BI/Lilly, Speaker, Novo Nordisk, Advisory Group Member, Novo Nordisk, Owner, Rio Weight Management Ltd. Nothing to Disclose: ÖT