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Efficacy and safety of once-weekly semaglutide vs exenatide ER after 56 Weeks in subjects with type 2 diabetes (SUSTAIN 3)
Oral Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S40–S64
cholinesterase were significantly correlated with the reduction of SSPG. Conclusion: Short-term tofogliflozin treatment significantly improved 24-h glucose profiles. The decline in body weight primarily resulted from the decrease in body fat. However, the risk of dehydration was not excluded because the subjects of this study were urged to drink adequate water during the treatment. Insulin sensitivity significantly improved likely due to the decrease in body fat mass. In addition, the improvement of hepatic steatosis may be involved in the amelioration of insulin resistance. OL05-3 Efficacy and safety of once-weekly semaglutide vs exenatide ER after 56 Weeks in subjects with type 2 diabetes (SUSTAIN 3) Andrew AHMANN1, Matthew CAPEHORN2, Guillaume CHARPENTIER3, Francesco DOTTA4, Elena HENKEL5, Ildiko LINGVAY6, Anders GAARSDAL HOLST7, Miriam ANNETT8, Vanita ARODA9. 1Harold Schnitzer Diabetes Health Center, OR, United States of America; 2Rotherham Institute for Obesity, Rotherham, United Kingdom; 3Centre Hospitalier Sud Francilien, Corbeil-Essonnes, France; 4University of Siena, Siena, Italy; 5Center for Clinical Studies, Technical University, Dresden, Germany; 6UT Southwestern Medical Center, Dallas, TX, United States of America; 7Novo Nordisk A/S, Søborg, Denmark, 8Novo Nordisk Inc., NJ, 9MedStar Health Research Institute, Hyattsville, MD, United States of America Semaglutide is a glucagon-like peptide-1 (GLP-1) analog in development for the treatment of type 2 diabetes (T2D). This study evaluated the efficacy, safety and tolerability of onceweekly subcutaneous semaglutide versus exenatide extendedrelease (ER) in subjects with T2D inadequately controlled on 1– 2 oral antidiabetic drugs (OADs: metformin, sulfonylureas and thiazolidinediones). In this phase 3, open-label study, 813 adults with T2D (HbA1c 7–10.5%) were randomized 1:1 to once-weekly semaglutide 1.0 mg or once-weekly exenatide ER 2.0 mg for 56 weeks. The primary endpoint was change in HbA1c from baseline to Week 56. Secondary efficacy endpoints included change in body weight (BW), blood pressure and other glycemic parameters. Baseline characteristics were similar in both arms; overall mean age 56.6 years, duration of T2D 9.2 years. Mean HbA1c (overall baseline mean 8.3%) was reduced by 1.5% with semaglutide and 0.9% with exenatide ER (estimated treatment difference vs exenatide ER [ETD] –0.62%; p < 0.0001). HbA1c <7% was achieved by 67% of semaglutide-treated subjects versus 40% with exenatide ER; 47% and 22% achieved HbA1c ≤6.5%, respectively. Mean BW (overall baseline mean 95.8 kg) was reduced by 5.6 kg with semaglutide and 1.9 kg with exenatide ER (ETD –3.73 kg; p < 0.0001). Adverse event (AE) rates were comparable between groups: 75.0% and 76.3% of subjects reported AEs with semaglutide and exenatide ER, respectively. Serious AEs were reported by 9.4% of subjects receiving semaglutide and 5.9% of subjects receiving exenatide ER (spread over multiple system organ classes). Two fatal events were reported in the semaglutide arm (both advanced stage neoplasms considered unrelated to treatment). The proportion of subjects discontinuing treatment due to AEs was 9.4% for semaglutide and 7.2% for exenatide ER. The most frequent AEs were gastrointestinal (GI), which were mainly mild or moderate in severity. GI AEs were reported by 41.8% and 33.3% of subjects receiving semaglutide and exenatide ER, respectively; 22.3% and 11.9% for nausea, 11.4% and 8.4% for diarrhea and 7.2% and 6.2% for vomiting. The proportion of subjects reporting nausea diminished over time in both groups. Injection site reactions were reported by 1.2% of subjects receiving semaglutide and 22.0% of subjects receiving exenatide ER.
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In conclusion, once-weekly subcutaneous semaglutide 1.0 mg was superior to exenatide ER 2.0 mg in improving glycemic control and reducing BW in subjects with T2D inadequately controlled on 1–2 OADs. Semaglutide was well tolerated, with a safety profile similar to that of other GLP-1 receptor agonists. OL05-4 Efficacy and safety of once-weekly semaglutide versus oncedaily insulin glargine in insulin-naïve subjects with type 2 diabetes (SUSTAIN 4) Vanita ARODA1, Stephen BAIN2, Bertrand CARIOU3, Milivoj PILETIC4, Ludger ROSE5, Eirik Quamme BERGAN6, Jeppe ZACHO6, J Hans DEVRIES7. 1MedStar Health Research Institute, Hyattsville, MD, United States of America; 2School of Medicine, Swansea University, Wales, United Kingdom; 3CHU Nantes, l’Institut du Thorax, Nantes, France; 4General Hospital, Novo Mesto, Slovenia; 5Münster Institute for Diabetes Research, Münster, Germany; 6Novo Nordisk A/S, Søborg, Denmark; 7Academic Medical Center, University of Amsterdam, Netherlands This trial evaluated the efficacy and safety of subcutaneous (s. c.) semaglutide versus insulin glargine (IGlar) in insulin-naïve subjects with T2D. In this phase 3a, randomized, open-label study, 1082 adults with T2D (HbA1c 7–10%) received semaglutide 0.5 mg (n = 362) or 1.0 mg (n = 360) once weekly or IGlar (n = 360; starting dose 10 IU/day) once daily for 30 weeks, added to stable metformin +/− sulfonylurea (SU). Investigators were instructed to titrate to a pre-breakfast self-monitored plasma glucose (SMPG) target of 4.0–5.5 mmol/L. Primary endpoint was change in HbA1c from baseline to Week 30. Mean HbA1c (baseline 8.2%) was reduced with semaglutide 0.5 and 1.0 mg by 1.2% and 1.6% versus 0.8% with IGlar (estimated treatment difference versus IGlar [ETD] –0.38% and –0.81%; p < 0.0001 for both). Mean IGlar dose at Week 30 was 29.2 IU/ day. HbA1c <7% was achieved by 57.5% and 73.3% of 0.5 and 1.0 mg semaglutide-treated subjects, respectively, versus 38.1% with IGlar. HbA1c ≤6.5% was achieved by 37.3%, 54.2% and 17.5% of subjects, respectively. Mean fasting plasma glucose (baseline 9.7 mmol/L) was reduced with semaglutide 0.5 and 1.0 mg by 2.1 and 2.7 mmol/L versus 2.1 mmol/L with IGlar (ETD 0.07 mmol/L [ p = 0.7] and –0.61 mmol/L [ p = 0.0002]). Mean 8-point SMPG (baseline 10.9 mmol/L) was reduced by 2.4, 2.9 and 2.4 mmol/L, respectively (ETD –0.07 mmol/L [ p = 0.6] and –0.58 mmol/L [ p < 0.0001]). Mean body weight (BW; baseline 93.4 kg) decreased with semaglutide 0.5 and 1.0 mg by 3.5 and 5.2 kg versus a 1.2 kg increase with IGlar (ETD –4.62 kg and –6.34 kg; p < 0.0001 for both). Proportions of subjects reporting adverse events (AEs) were 69.9%, 73.3% and 65.3% with semaglutide 0.5, 1.0 mg and IGlar, respectively; 6.1%, 4.7% and 5.0% reported serious AEs. Fatal AEs were reported in 4 semaglutide subjects and 2 IGlar subjects. Discontinuation due to AEs occurred in 5.5%, 7.5% and 1.1% of patients, respectively. The majority of discontinuations with semaglutide were due to gastrointestinal (GI) AEs; mild, transient GI AEs were the most common AEs with semaglutide. Proportions of subjects reporting GI AEs were: 21.3%, 22.2% and 3.6% for nausea; 16.3%, 19.2% and 4.4% for diarrhea; and 6.6%, 10.3% and 3.1% for vomiting. In conclusion, semaglutide (0.5 and 1.0 mg s.c. once weekly) provided superior glycemic control and BW reduction versus IGlar in patients with T2D treated with metformin +/− SU. Semaglutide was well tolerated with a safety profile similar to other GLP-1 receptor agonists.
cholinesterase were significantly correlated with the reduction of SSPG. Conclusion: Short-term tofogliflozin treatment significantly improved 24-h glucose profiles. The decline in body weight primarily resulted from the decrease in body fat. However, the risk of dehydration was not excluded because the subjects of this study were urged to drink adequate water during the treatment. Insulin sensitivity significantly improved likely due to the decrease in body fat mass. In addition, the improvement of hepatic steatosis may be involved in the amelioration of insulin resistance. OL05-3 Efficacy and safety of once-weekly semaglutide vs exenatide ER after 56 Weeks in subjects with type 2 diabetes (SUSTAIN 3) Andrew AHMANN1, Matthew CAPEHORN2, Guillaume CHARPENTIER3, Francesco DOTTA4, Elena HENKEL5, Ildiko LINGVAY6, Anders GAARSDAL HOLST7, Miriam ANNETT8, Vanita ARODA9. 1Harold Schnitzer Diabetes Health Center, OR, United States of America; 2Rotherham Institute for Obesity, Rotherham, United Kingdom; 3Centre Hospitalier Sud Francilien, Corbeil-Essonnes, France; 4University of Siena, Siena, Italy; 5Center for Clinical Studies, Technical University, Dresden, Germany; 6UT Southwestern Medical Center, Dallas, TX, United States of America; 7Novo Nordisk A/S, Søborg, Denmark, 8Novo Nordisk Inc., NJ, 9MedStar Health Research Institute, Hyattsville, MD, United States of America Semaglutide is a glucagon-like peptide-1 (GLP-1) analog in development for the treatment of type 2 diabetes (T2D). This study evaluated the efficacy, safety and tolerability of onceweekly subcutaneous semaglutide versus exenatide extendedrelease (ER) in subjects with T2D inadequately controlled on 1– 2 oral antidiabetic drugs (OADs: metformin, sulfonylureas and thiazolidinediones). In this phase 3, open-label study, 813 adults with T2D (HbA1c 7–10.5%) were randomized 1:1 to once-weekly semaglutide 1.0 mg or once-weekly exenatide ER 2.0 mg for 56 weeks. The primary endpoint was change in HbA1c from baseline to Week 56. Secondary efficacy endpoints included change in body weight (BW), blood pressure and other glycemic parameters. Baseline characteristics were similar in both arms; overall mean age 56.6 years, duration of T2D 9.2 years. Mean HbA1c (overall baseline mean 8.3%) was reduced by 1.5% with semaglutide and 0.9% with exenatide ER (estimated treatment difference vs exenatide ER [ETD] –0.62%; p < 0.0001). HbA1c <7% was achieved by 67% of semaglutide-treated subjects versus 40% with exenatide ER; 47% and 22% achieved HbA1c ≤6.5%, respectively. Mean BW (overall baseline mean 95.8 kg) was reduced by 5.6 kg with semaglutide and 1.9 kg with exenatide ER (ETD –3.73 kg; p < 0.0001). Adverse event (AE) rates were comparable between groups: 75.0% and 76.3% of subjects reported AEs with semaglutide and exenatide ER, respectively. Serious AEs were reported by 9.4% of subjects receiving semaglutide and 5.9% of subjects receiving exenatide ER (spread over multiple system organ classes). Two fatal events were reported in the semaglutide arm (both advanced stage neoplasms considered unrelated to treatment). The proportion of subjects discontinuing treatment due to AEs was 9.4% for semaglutide and 7.2% for exenatide ER. The most frequent AEs were gastrointestinal (GI), which were mainly mild or moderate in severity. GI AEs were reported by 41.8% and 33.3% of subjects receiving semaglutide and exenatide ER, respectively; 22.3% and 11.9% for nausea, 11.4% and 8.4% for diarrhea and 7.2% and 6.2% for vomiting. The proportion of subjects reporting nausea diminished over time in both groups. Injection site reactions were reported by 1.2% of subjects receiving semaglutide and 22.0% of subjects receiving exenatide ER.
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In conclusion, once-weekly subcutaneous semaglutide 1.0 mg was superior to exenatide ER 2.0 mg in improving glycemic control and reducing BW in subjects with T2D inadequately controlled on 1–2 OADs. Semaglutide was well tolerated, with a safety profile similar to that of other GLP-1 receptor agonists. OL05-4 Efficacy and safety of once-weekly semaglutide versus oncedaily insulin glargine in insulin-naïve subjects with type 2 diabetes (SUSTAIN 4) Vanita ARODA1, Stephen BAIN2, Bertrand CARIOU3, Milivoj PILETIC4, Ludger ROSE5, Eirik Quamme BERGAN6, Jeppe ZACHO6, J Hans DEVRIES7. 1MedStar Health Research Institute, Hyattsville, MD, United States of America; 2School of Medicine, Swansea University, Wales, United Kingdom; 3CHU Nantes, l’Institut du Thorax, Nantes, France; 4General Hospital, Novo Mesto, Slovenia; 5Münster Institute for Diabetes Research, Münster, Germany; 6Novo Nordisk A/S, Søborg, Denmark; 7Academic Medical Center, University of Amsterdam, Netherlands This trial evaluated the efficacy and safety of subcutaneous (s. c.) semaglutide versus insulin glargine (IGlar) in insulin-naïve subjects with T2D. In this phase 3a, randomized, open-label study, 1082 adults with T2D (HbA1c 7–10%) received semaglutide 0.5 mg (n = 362) or 1.0 mg (n = 360) once weekly or IGlar (n = 360; starting dose 10 IU/day) once daily for 30 weeks, added to stable metformin +/− sulfonylurea (SU). Investigators were instructed to titrate to a pre-breakfast self-monitored plasma glucose (SMPG) target of 4.0–5.5 mmol/L. Primary endpoint was change in HbA1c from baseline to Week 30. Mean HbA1c (baseline 8.2%) was reduced with semaglutide 0.5 and 1.0 mg by 1.2% and 1.6% versus 0.8% with IGlar (estimated treatment difference versus IGlar [ETD] –0.38% and –0.81%; p < 0.0001 for both). Mean IGlar dose at Week 30 was 29.2 IU/ day. HbA1c <7% was achieved by 57.5% and 73.3% of 0.5 and 1.0 mg semaglutide-treated subjects, respectively, versus 38.1% with IGlar. HbA1c ≤6.5% was achieved by 37.3%, 54.2% and 17.5% of subjects, respectively. Mean fasting plasma glucose (baseline 9.7 mmol/L) was reduced with semaglutide 0.5 and 1.0 mg by 2.1 and 2.7 mmol/L versus 2.1 mmol/L with IGlar (ETD 0.07 mmol/L [ p = 0.7] and –0.61 mmol/L [ p = 0.0002]). Mean 8-point SMPG (baseline 10.9 mmol/L) was reduced by 2.4, 2.9 and 2.4 mmol/L, respectively (ETD –0.07 mmol/L [ p = 0.6] and –0.58 mmol/L [ p < 0.0001]). Mean body weight (BW; baseline 93.4 kg) decreased with semaglutide 0.5 and 1.0 mg by 3.5 and 5.2 kg versus a 1.2 kg increase with IGlar (ETD –4.62 kg and –6.34 kg; p < 0.0001 for both). Proportions of subjects reporting adverse events (AEs) were 69.9%, 73.3% and 65.3% with semaglutide 0.5, 1.0 mg and IGlar, respectively; 6.1%, 4.7% and 5.0% reported serious AEs. Fatal AEs were reported in 4 semaglutide subjects and 2 IGlar subjects. Discontinuation due to AEs occurred in 5.5%, 7.5% and 1.1% of patients, respectively. The majority of discontinuations with semaglutide were due to gastrointestinal (GI) AEs; mild, transient GI AEs were the most common AEs with semaglutide. Proportions of subjects reporting GI AEs were: 21.3%, 22.2% and 3.6% for nausea; 16.3%, 19.2% and 4.4% for diarrhea; and 6.6%, 10.3% and 3.1% for vomiting. In conclusion, semaglutide (0.5 and 1.0 mg s.c. once weekly) provided superior glycemic control and BW reduction versus IGlar in patients with T2D treated with metformin +/− SU. Semaglutide was well tolerated with a safety profile similar to other GLP-1 receptor agonists.