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Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in subjects with type 2 diabetes (SUSTAIN 1)
Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65–S211
control in Taiwan. One hundred and sixty type 2 diabetic patients were recruited from China Medical University Hospital in Taichung, Taiwan. Biochemical data, such as plasma fasting sugar, HbA1c, total cholesterol, triglyceride, HDL-C, and LDL-C, were collected from medical records. Diet was assessed by a validated food frequency questionnaire which composed of 118 food items, and categorized to 23 food groups. Diabetic patient’s dietary pattern was analyzed by principle component analysis. Confounders related to both diet and biochemical indices including age, gender, BMI, energy intakes, and physical activity were assessed. Multiple logistic regression analyses were used to predict odds ratios of poor blood biochemical control after adjustment of confounders. Mean age of the study subjects was 57.46 ± 10.67 year-old and had 2.8 year of diabetes history. Four dietary patterns were identified, pattern I (high meat, fish, vegetable, nut and oil), pattern 2 (high refined rice, starchy root, and fish), pattern 3 (high refined rice, meat product, sugar drink, low whole grain, vegetable, nut), and pattern 4 (high vegetable, non-sugar drink, low starchy root, dairy product, and snack). Mean age, energy intake, BMI, and sex proportion were significantly different among different patterns. Compared to pattern 4, the odds ratio of high HbA1c (≥7%) was 3.66 (95% CI 1.21–11.05) for pattern 1 and 2.52 (95% CI 1.00–6.39) for pattern 3 after gender, age, energy intake, and BMI adjustment. Odds ratio of high plasma fasting sugar (>130 mg/dL) was 2.67 (95% CI 1.08–6.65) for pattern 3 compared to pattern 4. For female patients, odds ratio of low HDL-C (<50 mg/dL) was 0.11 (95% CI 0.02–0.80) for pattern 1 compared to pattern 4. In the present study, clusters of food groups might not be representative for Taiwanese diabetic patients; however, different dietary patterns were possible to influence blood sugar and lipid control among diabetic patients. More consumption of vegetables, fish and nuts, less sugar drinks and snacks are beneficial for diabetic treatment. PD-94 Relationship between indices of daily glycemic variability and long-term glucose fluctuations Yuusuke WATANABE1 *, Yoshifumi SAISHO1, Rie MURAKAMI1, Jun INAISHI1, Kenji KANEKO1, Hiroshi ITOH1. 1Department of Internal Medicine, Keio University School of Medicine, Japan Purpose: We investigated the relationship between indices of daily glycemic variability and long-term glucose fluctuations. Methods: A total of 123 patients with diabetes (22 patients with type 1 diabetes; 9 males, age 53 ± 16, HbA1c 7.9 ± 1.4%, GA 25.0 ± 6.0%, and 101 patients with type 2 diabetes; 80 males, age 69 ± 10, HbA1c 6.8 ± 0.8%, GA 18.8 ± 3.9%) who underwent continuous glucose monitoring (CGM) in outpatient settings were enrolled in this study. We evaluated the daily glycemic variability from the CGM data as follows; mean glucose level, standard deviation (SD), time of hyper- and hypoglycemia, area under the curve (AUC) of hyper- and hypoglycemia, Jindex, hyperglycemic index, hypoglycemic index, index of glycemic control (ICG), continuous overlapping net glycemic action (CONGA), mean amplitude of glycemic excursion (MAGE), M-value, mean of the daily differences (MODD). In addition, Coefficient of variation (CV) of HbA1c and GA were calculated from HbA1c and GA measured before and after 3 years from CGM measurement. Result: Both CV-HbA1c and CV-GA were correlated with mean glucose level, SD, time of hyperglycemia, AUC of hyperglycemia, J-index, hyperglycemic index, ICG, MODD, MAGE and M-value but were not correlated with time of hypoglycemia, AUC of hypoglycemia, hypoglycemic index, and CONGA-1. Especially, CV-HbA1c was strongly correlated with mean glucose level, time of hyperglycemia, AUC of hyperglycemia, J-index and M-value (r = 0.4), and so was CV-GA. Serum Cpeptide level was negatively correlated with the indices of daily glycemic variability, CV-HbA1c and CV-GA, and was also
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correlated with GA/HbA1c. GA/HbA1c was correlated with the indices of daily glycemic variability, but not correlated with CV-HbA1c or CV-GA. These results were not changed when only the patients with type 2 diabetes were included in the analysis. Conclusion: The indices of daily glycemic variability were correlated with long-term glucose fluctuations, but were not correlated with the indices of hypoglycemia. These findings suggest that CV-HbA1c and CV-GA may not reflect the risk of hypoglycemia. And β-cell function was correlated with both daily glycemic variability and long-term glucose fluctuations. Clarifying the features of various indices of glycemic variability and the relationship among them could make these indices more useful in clinical practice. PD-95 Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in subjects with type 2 diabetes (SUSTAIN 1) Shin-ichi HARASHIMA1 *, Christopher SORLI2, George TSOUKAS3, Jeffrey UNGER4, Julie DERVING KARSBØL5, Thomas HANSEN5, Stephen BAIN6. 1Graduate School of Medicine, Kyoto University, Kyoto, Japan; 2Billings Clinic Research Center, Billings, MT, United States of America; 3Department of Medicine, McGill University, Montreal, Canada; 4Catalina Research Institute, Chino, CA, United States of America; 5Novo Nordisk A/S, Søborg, Denmark; 6School of Medicine, Swansea University, Wales, United Kingdom 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 subcutaneous (s.c.) semaglutide monotherapy versus placebo in drug-naïve subjects with T2D. In this phase 3, double-blind study, 388 adults with T2D (HbA1c 7–10%) were randomized to s.c. semaglutide 0.5 mg or 1.0 mg once weekly or placebo for 30 weeks, including 4–8 weeks of dose escalation. Primary endpoint was change in HbA1c from baseline to Week 30. Mean HbA1c (baseline 8.1%) was reduced with semaglutide 0.5 mg and 1.0 mg by 1.5% and 1.6%, respectively, versus <0.1% in the placebo group (estimated treatment difference versus placebo [ETD] −1.4% and −1.5%; p < 0.0001 for both). HbA1c <7% was achieved by 74% and 72% of 0.5 mg and 1.0 mg semaglutide-treated subjects, versus 25% in the placebo group. The corresponding proportions of subjects achieving HbA1c ≤6.5% were 59%, 60% and 13%. Mean fasting plasma glucose (baseline 9.8 mmol/L) was reduced with semaglutide 0.5 mg and 1.0 mg by 2.5 mmol/L and 2.3 mmol/L, respectively, versus 0.6 mmol/L with placebo (ETD −2.0 mmol/L and −1.8 mmol/L; p < 0.0001 for both). Mean body weight (BW; baseline 91.9 kg) was significantly decreased with semaglutide 0.5 mg and 1.0 mg by 3.7 kg and 4.5 kg, respectively, versus 1.0 kg in the placebo group (ETD −2.8 kg and −3.6 kg; p < 0.0001 for both). Changes in blood pressure (baseline 128.8/79.3 mmHg) were comparable between the semaglutide 0.5 mg, 1.0 mg and placebo groups. Adverse event (AE) and serious AE (SAE) rates were comparable between groups: 64.1%, 56.2% and 53.5% of patients reported AEs with semaglutide 0.5 mg, 1.0 mg and placebo, respectively, and 5.5%, 5.4% and 3.9% reported SAEs. Proportions of patients discontinuing due to AEs were 6.3%, 5.4% and 2.3% for semaglutide 0.5 mg, 1.0 mg and placebo. Proportions of subjects reporting gastrointestinal AEs in the 0.5 mg, 1.0 mg and placebo groups were 20.3%, 23.8% and 7.8% for nausea; 3.9%, 6.9% and 1.6% for vomiting; and 12.5%, 10.8% and 2.3% for diarrhea. Nausea rate diminished over time. In conclusion, semaglutide monotherapy, s.c. once-weekly doses of 0.5 mg and 1.0 mg, significantly improved glycemic control and reduced BW versus placebo in patients with T2D. Semaglutide was well tolerated, with a safety profile similar to that of other GLP-1 receptor agonists.
control in Taiwan. One hundred and sixty type 2 diabetic patients were recruited from China Medical University Hospital in Taichung, Taiwan. Biochemical data, such as plasma fasting sugar, HbA1c, total cholesterol, triglyceride, HDL-C, and LDL-C, were collected from medical records. Diet was assessed by a validated food frequency questionnaire which composed of 118 food items, and categorized to 23 food groups. Diabetic patient’s dietary pattern was analyzed by principle component analysis. Confounders related to both diet and biochemical indices including age, gender, BMI, energy intakes, and physical activity were assessed. Multiple logistic regression analyses were used to predict odds ratios of poor blood biochemical control after adjustment of confounders. Mean age of the study subjects was 57.46 ± 10.67 year-old and had 2.8 year of diabetes history. Four dietary patterns were identified, pattern I (high meat, fish, vegetable, nut and oil), pattern 2 (high refined rice, starchy root, and fish), pattern 3 (high refined rice, meat product, sugar drink, low whole grain, vegetable, nut), and pattern 4 (high vegetable, non-sugar drink, low starchy root, dairy product, and snack). Mean age, energy intake, BMI, and sex proportion were significantly different among different patterns. Compared to pattern 4, the odds ratio of high HbA1c (≥7%) was 3.66 (95% CI 1.21–11.05) for pattern 1 and 2.52 (95% CI 1.00–6.39) for pattern 3 after gender, age, energy intake, and BMI adjustment. Odds ratio of high plasma fasting sugar (>130 mg/dL) was 2.67 (95% CI 1.08–6.65) for pattern 3 compared to pattern 4. For female patients, odds ratio of low HDL-C (<50 mg/dL) was 0.11 (95% CI 0.02–0.80) for pattern 1 compared to pattern 4. In the present study, clusters of food groups might not be representative for Taiwanese diabetic patients; however, different dietary patterns were possible to influence blood sugar and lipid control among diabetic patients. More consumption of vegetables, fish and nuts, less sugar drinks and snacks are beneficial for diabetic treatment. PD-94 Relationship between indices of daily glycemic variability and long-term glucose fluctuations Yuusuke WATANABE1 *, Yoshifumi SAISHO1, Rie MURAKAMI1, Jun INAISHI1, Kenji KANEKO1, Hiroshi ITOH1. 1Department of Internal Medicine, Keio University School of Medicine, Japan Purpose: We investigated the relationship between indices of daily glycemic variability and long-term glucose fluctuations. Methods: A total of 123 patients with diabetes (22 patients with type 1 diabetes; 9 males, age 53 ± 16, HbA1c 7.9 ± 1.4%, GA 25.0 ± 6.0%, and 101 patients with type 2 diabetes; 80 males, age 69 ± 10, HbA1c 6.8 ± 0.8%, GA 18.8 ± 3.9%) who underwent continuous glucose monitoring (CGM) in outpatient settings were enrolled in this study. We evaluated the daily glycemic variability from the CGM data as follows; mean glucose level, standard deviation (SD), time of hyper- and hypoglycemia, area under the curve (AUC) of hyper- and hypoglycemia, Jindex, hyperglycemic index, hypoglycemic index, index of glycemic control (ICG), continuous overlapping net glycemic action (CONGA), mean amplitude of glycemic excursion (MAGE), M-value, mean of the daily differences (MODD). In addition, Coefficient of variation (CV) of HbA1c and GA were calculated from HbA1c and GA measured before and after 3 years from CGM measurement. Result: Both CV-HbA1c and CV-GA were correlated with mean glucose level, SD, time of hyperglycemia, AUC of hyperglycemia, J-index, hyperglycemic index, ICG, MODD, MAGE and M-value but were not correlated with time of hypoglycemia, AUC of hypoglycemia, hypoglycemic index, and CONGA-1. Especially, CV-HbA1c was strongly correlated with mean glucose level, time of hyperglycemia, AUC of hyperglycemia, J-index and M-value (r = 0.4), and so was CV-GA. Serum Cpeptide level was negatively correlated with the indices of daily glycemic variability, CV-HbA1c and CV-GA, and was also
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correlated with GA/HbA1c. GA/HbA1c was correlated with the indices of daily glycemic variability, but not correlated with CV-HbA1c or CV-GA. These results were not changed when only the patients with type 2 diabetes were included in the analysis. Conclusion: The indices of daily glycemic variability were correlated with long-term glucose fluctuations, but were not correlated with the indices of hypoglycemia. These findings suggest that CV-HbA1c and CV-GA may not reflect the risk of hypoglycemia. And β-cell function was correlated with both daily glycemic variability and long-term glucose fluctuations. Clarifying the features of various indices of glycemic variability and the relationship among them could make these indices more useful in clinical practice. PD-95 Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in subjects with type 2 diabetes (SUSTAIN 1) Shin-ichi HARASHIMA1 *, Christopher SORLI2, George TSOUKAS3, Jeffrey UNGER4, Julie DERVING KARSBØL5, Thomas HANSEN5, Stephen BAIN6. 1Graduate School of Medicine, Kyoto University, Kyoto, Japan; 2Billings Clinic Research Center, Billings, MT, United States of America; 3Department of Medicine, McGill University, Montreal, Canada; 4Catalina Research Institute, Chino, CA, United States of America; 5Novo Nordisk A/S, Søborg, Denmark; 6School of Medicine, Swansea University, Wales, United Kingdom 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 subcutaneous (s.c.) semaglutide monotherapy versus placebo in drug-naïve subjects with T2D. In this phase 3, double-blind study, 388 adults with T2D (HbA1c 7–10%) were randomized to s.c. semaglutide 0.5 mg or 1.0 mg once weekly or placebo for 30 weeks, including 4–8 weeks of dose escalation. Primary endpoint was change in HbA1c from baseline to Week 30. Mean HbA1c (baseline 8.1%) was reduced with semaglutide 0.5 mg and 1.0 mg by 1.5% and 1.6%, respectively, versus <0.1% in the placebo group (estimated treatment difference versus placebo [ETD] −1.4% and −1.5%; p < 0.0001 for both). HbA1c <7% was achieved by 74% and 72% of 0.5 mg and 1.0 mg semaglutide-treated subjects, versus 25% in the placebo group. The corresponding proportions of subjects achieving HbA1c ≤6.5% were 59%, 60% and 13%. Mean fasting plasma glucose (baseline 9.8 mmol/L) was reduced with semaglutide 0.5 mg and 1.0 mg by 2.5 mmol/L and 2.3 mmol/L, respectively, versus 0.6 mmol/L with placebo (ETD −2.0 mmol/L and −1.8 mmol/L; p < 0.0001 for both). Mean body weight (BW; baseline 91.9 kg) was significantly decreased with semaglutide 0.5 mg and 1.0 mg by 3.7 kg and 4.5 kg, respectively, versus 1.0 kg in the placebo group (ETD −2.8 kg and −3.6 kg; p < 0.0001 for both). Changes in blood pressure (baseline 128.8/79.3 mmHg) were comparable between the semaglutide 0.5 mg, 1.0 mg and placebo groups. Adverse event (AE) and serious AE (SAE) rates were comparable between groups: 64.1%, 56.2% and 53.5% of patients reported AEs with semaglutide 0.5 mg, 1.0 mg and placebo, respectively, and 5.5%, 5.4% and 3.9% reported SAEs. Proportions of patients discontinuing due to AEs were 6.3%, 5.4% and 2.3% for semaglutide 0.5 mg, 1.0 mg and placebo. Proportions of subjects reporting gastrointestinal AEs in the 0.5 mg, 1.0 mg and placebo groups were 20.3%, 23.8% and 7.8% for nausea; 3.9%, 6.9% and 1.6% for vomiting; and 12.5%, 10.8% and 2.3% for diarrhea. Nausea rate diminished over time. In conclusion, semaglutide monotherapy, s.c. once-weekly doses of 0.5 mg and 1.0 mg, significantly improved glycemic control and reduced BW versus placebo in patients with T2D. Semaglutide was well tolerated, with a safety profile similar to that of other GLP-1 receptor agonists.