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A1C Improvement with Liraglutide Evaluated by Baseline BMI
Abstracts / Can J Diabetes 37 (2013) S13eS84
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of hypoglycemia (CBG3.9 mmol/L) decreased significantly in 1 unit but increased in 3 units. Conclusions: Despite a small increase in hypoglycemia incidence, the implementation of BPC has led to substantial improvements in the control of hyperglycemia among hospitalized patients across most hospital units. Future efforts are needed to continue BPCrelated education and to investigate compliance with the protocol on units not achieving desired outcomes.
92 The Effect of Liraglutide on A1C and Body Weight is Largely Independent of Diabetes Duration JOCHEN SEUFERT, TIMOTHY BAILEY, MORTEN DONSMARK, STEPHAN PERRON*, MICHAEL NAUCK Freiburg, Germany; Escondido, CA; Søborg, Denmark; Mississauga, ON; Bad Lauterberg, Germany Background and Aims: The LEAD phase 3 clinical program demonstrated liraglutide’s effectiveness across the continuum of type 2 diabetes (T2D); however, the effect of baseline diabetes duration is unclear. Using 26/28-week data from 7 phase 3 trials, this post-hoc, pooled analysis evaluated the effect of diabetes duration on changes in A1C and body weight from baseline with liraglutide 1.8 mg (n¼1581), liraglutide 1.2 mg (n¼1117) and placebo (n¼524). Materials and Methods: The slope for change in A1C or body weight vs. diabetes duration was determined by linear regression. The statistical model included the baseline value of the endpoint, diabetes duration and age as continuous covariates. Previous treatment and country were categorical covariates. Results: Across treatment arms, diabetes duration ranged from <1 to >40 years, with a mean of w8 years for pooled groups. There was a trend toward greater A1C reduction with shorter diabetes duration with liraglutide but this was not clinically relevant (Figure 1); statistical significance was achieved for pooled liraglutide 1.2 mg group (p<0.05) but the difference only equated to e0.2% A1C/10-
Figure 2. Effect of baseline diabetes duration (DD) on change in body weight.
year shorter diabetes duration. The effect of liraglutide on body weight was independent of diabetes duration (Figure 2). Conclusion: The proven effectiveness of liraglutide to reduce A1C and body weight is largely independent of diabetes duration. Therefore, liraglutide can be successfully used across the continuum of T2D.
93 A1C Improvement with Liraglutide Evaluated by Baseline BMI EDUARD MONTANYA, STEPHEN COLAGIURI, LAWRENCE BLONDE, CLAUS BO SVENDSEN, LUCETTE FARAH*, MICHAEL NAUCK Barcelona, Spain; Sydney, Australia; New Orleans, LA; Søborg, Denmark; Mississauga, ON; Bad Lauterberg, Germany
Figure 1. Effect of baseline diabetes duration (DD) on change in A1C.
The LEAD phase 3 clinical trial program demonstrated both improved glycemic control and mean weight loss in patients with type 2 diabetes with 1.2 mg or 1.8 mg liraglutide treatment. It is unclear whether the glycemic response with liraglutide is dependent on patients’ baseline BMI. In this post-hoc pooled analysis of 7 clinical trials (LEAD-1e6 and LiraeDPP-4i, n¼5100), the relationship between A1C response and baseline BMI was explored. Data from each treatment arm were modeled across trials, including pooled analyses of liraglutide and placebo, accounting for baseline A1C, country, trial and prior treatment. Across treatment arms, mean BMI at baseline ranged from 29.8 to 33.7 kg/m2. Maximum baseline BMI was 45 kg/m2 (based on inclusion criteria). Models used 26/28-week data for change in A1C from baseline using the intent-to-treat population, last observation carried forward. The slope of baseline BMI vs. change in A1C for pooled liraglutide 1.8 mg data is shown in Figure 1A, and Forest plots describing the impact of baseline BMI on A1C improvement for liraglutide 1.2 mg and 1.8 mg and placebo for pooled and individual trials are shown in Figure 1B: a slight negative correlation was seen with liraglutide 1.8 mg (e0.011 [95%CI: e0.020, e0.002]), but no association was observed with liraglutide 1.2 mg and placebo. The effect with liraglutide 1.8 mg was small: a 10 kg/m2 higher BMI corresponded to a difference in
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Abstracts / Can J Diabetes 37 (2013) S13eS84
extremity amputation and low foot examination rates. In response, the Ottawa Hospital made diabetes foot ulcer prevention a quality improvement priority. Using formal QI methods, foot ulcer risk assessment and stratification, referral processes and self management education were standardized and implemented at 15 weekly diabetes clinics attended by 11 endocrinologists, multiple rotating medical residents and 9 nurses over an 8-month period. The Registered Nurses Association of Ontario and Canadian Diabetes Association practice guidelines informed the process. QI strategies including chart audits, learning sessions, current and future state mapping, and stakeholder surveys, enabled an understanding of practice variations, user needs and concerns and environmental factors impacting care. Evidence-based clinical protocols, documents and resources were developed, tested and adjusted through a series of rapid change cycles. Performance expectations and targets were developed and shared across disciplines. Progress was measured weekly and communicated regularly. Significant improvements were achieved. More than 90% of newly referred patients receive a standardized, 5-item foot exam and risk assessment with over 30% presenting as “higher” risk for ulcers. Patients are informed of their risk factors, education is provided, referrals made for modifiable risk and charts flagged for follow up. Patients and practitioners are highly satisfied with the practice changes. We have demonstrated that even in busy, complex environments, practice can be standardized and change sustained using QI methods.
95 Meta-Analysis of Randomized Controlled Trials of Lixisenatide as Add On to Basal Insulin and/or Oral Antihyperglycemic Agents in Patients with Type 2 Diabetes Mellitus RONALD M. GOLDENBERG*, MANUEL PUIG-DOMINGO, VIVIAN FONSECA, EDWARD C. WANG, JAY LIN, MELANIE J. DAVIES, FRANCISCO JOSÉ TINAHONES, BERNARD CHARBONNEL Thornhill, ON; Barcelona, Spain; New Orleans, LA; Bridgewater, NJ; Flemington, NJ; Leicester, UK; Málaga, Spain; Nantes, France
Figure 1. A1C improvement with 1.8 mg liraglutide is marginally greater at higher baseline BMI. (a) Pooled analysis of the correlation of change in A1C from baseline vs. baseline BMI for liraglutide 1.8 mg: a crude regression line of the analysis is shown in bold (no modeling done), the model-adjusted slope is 0.011% per kg/m2. (b) Forest plots showing the estimated influence of baseline BMI on change in A1C for liraglutide 1.2 mg, 1.8 mg and placebo. Data are modeled estimates with 95% confidence intervals.
A1C reduction of 0.11%. In conclusion, there was no clinically relevant A1C improvement associated with liraglutide with higher baseline BMI (up to 45 kg/m2).
94 Implementing Standardized Best Practices for Reducing Diabetes Foot Ulcer Risk in a Large Academic Clinic JANINE C. MALCOLM*, SHARON M. BREZ, SHERYL M. IZZI, BRIGITTE SKINNER Ottawa, ON Foot ulcers are a common, often preventable complication of diabetes associated with burdens and costs. Recent reports indicate eastern Ontario has a disproportionately high incidence of lower
Aims: To evaluate the safety and efficacy of lixisenatide in combination with basal insulin oral antihyperglycemic agents in patients with type 2 diabetes mellitus (T2DM). Methods: This was a meta-analysis of 1198 patients from 3 phase III, randomized, placebo-controlled trials from the lixisenatide clinical development program (GetGoal-L, GetGoal-Duo-1 and GetGoal-L-Asia). Results: Mean baseline characteristics: age: 57.2 years; diabetes duration: 11.7 years; body mass index: 30.3 kg/m2; mean A1C was 8.2% for lixisenatide vs. 8.1% for placebo. At endpoint, mean A1C was 7.5% vs. 7.9% for lixisenatide and placebo, respectively. A significantly higher proportion of lixisenatide patients achieved A1C <7% vs. placebo (odds ratio [95% CI]: 3.7 [1.6, 8.2], p¼0.0016). Lixisenatide was more than 3 times more likely than placebo to result in A1C <7% and no weight gain (odds ratio [95% CI]: 3.4 [1.7, 6.8], p¼0.0008), more than 2.5 times more likely than placebo to result in A1C <7% and no documented symptomatic hypoglycemia (odds ratio [95% CI]: 2.7 [1.3, 5.4], p¼0.0073) and more than 2.5 times more likely to result in A1C <7% and no weight gain and no documented symptomatic hypoglycemia (odds ratio [95% CI]: 2.6 [1.5, 4.7], p¼0.0009). Conclusions: In patients with T2DM, lixisenatide in combination with basal insulin antihyperglycemic agents is significantly more effective than placebo in achieving A1C <7%, and is more than 2.5 times more likely to result in A1C <7% with no documented hypoglycemia and no weight gain. Lixisenatide is a treatment option as add on to treatment with basal insulin.
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of hypoglycemia (CBG3.9 mmol/L) decreased significantly in 1 unit but increased in 3 units. Conclusions: Despite a small increase in hypoglycemia incidence, the implementation of BPC has led to substantial improvements in the control of hyperglycemia among hospitalized patients across most hospital units. Future efforts are needed to continue BPCrelated education and to investigate compliance with the protocol on units not achieving desired outcomes.
92 The Effect of Liraglutide on A1C and Body Weight is Largely Independent of Diabetes Duration JOCHEN SEUFERT, TIMOTHY BAILEY, MORTEN DONSMARK, STEPHAN PERRON*, MICHAEL NAUCK Freiburg, Germany; Escondido, CA; Søborg, Denmark; Mississauga, ON; Bad Lauterberg, Germany Background and Aims: The LEAD phase 3 clinical program demonstrated liraglutide’s effectiveness across the continuum of type 2 diabetes (T2D); however, the effect of baseline diabetes duration is unclear. Using 26/28-week data from 7 phase 3 trials, this post-hoc, pooled analysis evaluated the effect of diabetes duration on changes in A1C and body weight from baseline with liraglutide 1.8 mg (n¼1581), liraglutide 1.2 mg (n¼1117) and placebo (n¼524). Materials and Methods: The slope for change in A1C or body weight vs. diabetes duration was determined by linear regression. The statistical model included the baseline value of the endpoint, diabetes duration and age as continuous covariates. Previous treatment and country were categorical covariates. Results: Across treatment arms, diabetes duration ranged from <1 to >40 years, with a mean of w8 years for pooled groups. There was a trend toward greater A1C reduction with shorter diabetes duration with liraglutide but this was not clinically relevant (Figure 1); statistical significance was achieved for pooled liraglutide 1.2 mg group (p<0.05) but the difference only equated to e0.2% A1C/10-
Figure 2. Effect of baseline diabetes duration (DD) on change in body weight.
year shorter diabetes duration. The effect of liraglutide on body weight was independent of diabetes duration (Figure 2). Conclusion: The proven effectiveness of liraglutide to reduce A1C and body weight is largely independent of diabetes duration. Therefore, liraglutide can be successfully used across the continuum of T2D.
93 A1C Improvement with Liraglutide Evaluated by Baseline BMI EDUARD MONTANYA, STEPHEN COLAGIURI, LAWRENCE BLONDE, CLAUS BO SVENDSEN, LUCETTE FARAH*, MICHAEL NAUCK Barcelona, Spain; Sydney, Australia; New Orleans, LA; Søborg, Denmark; Mississauga, ON; Bad Lauterberg, Germany
Figure 1. Effect of baseline diabetes duration (DD) on change in A1C.
The LEAD phase 3 clinical trial program demonstrated both improved glycemic control and mean weight loss in patients with type 2 diabetes with 1.2 mg or 1.8 mg liraglutide treatment. It is unclear whether the glycemic response with liraglutide is dependent on patients’ baseline BMI. In this post-hoc pooled analysis of 7 clinical trials (LEAD-1e6 and LiraeDPP-4i, n¼5100), the relationship between A1C response and baseline BMI was explored. Data from each treatment arm were modeled across trials, including pooled analyses of liraglutide and placebo, accounting for baseline A1C, country, trial and prior treatment. Across treatment arms, mean BMI at baseline ranged from 29.8 to 33.7 kg/m2. Maximum baseline BMI was 45 kg/m2 (based on inclusion criteria). Models used 26/28-week data for change in A1C from baseline using the intent-to-treat population, last observation carried forward. The slope of baseline BMI vs. change in A1C for pooled liraglutide 1.8 mg data is shown in Figure 1A, and Forest plots describing the impact of baseline BMI on A1C improvement for liraglutide 1.2 mg and 1.8 mg and placebo for pooled and individual trials are shown in Figure 1B: a slight negative correlation was seen with liraglutide 1.8 mg (e0.011 [95%CI: e0.020, e0.002]), but no association was observed with liraglutide 1.2 mg and placebo. The effect with liraglutide 1.8 mg was small: a 10 kg/m2 higher BMI corresponded to a difference in
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Abstracts / Can J Diabetes 37 (2013) S13eS84
extremity amputation and low foot examination rates. In response, the Ottawa Hospital made diabetes foot ulcer prevention a quality improvement priority. Using formal QI methods, foot ulcer risk assessment and stratification, referral processes and self management education were standardized and implemented at 15 weekly diabetes clinics attended by 11 endocrinologists, multiple rotating medical residents and 9 nurses over an 8-month period. The Registered Nurses Association of Ontario and Canadian Diabetes Association practice guidelines informed the process. QI strategies including chart audits, learning sessions, current and future state mapping, and stakeholder surveys, enabled an understanding of practice variations, user needs and concerns and environmental factors impacting care. Evidence-based clinical protocols, documents and resources were developed, tested and adjusted through a series of rapid change cycles. Performance expectations and targets were developed and shared across disciplines. Progress was measured weekly and communicated regularly. Significant improvements were achieved. More than 90% of newly referred patients receive a standardized, 5-item foot exam and risk assessment with over 30% presenting as “higher” risk for ulcers. Patients are informed of their risk factors, education is provided, referrals made for modifiable risk and charts flagged for follow up. Patients and practitioners are highly satisfied with the practice changes. We have demonstrated that even in busy, complex environments, practice can be standardized and change sustained using QI methods.
95 Meta-Analysis of Randomized Controlled Trials of Lixisenatide as Add On to Basal Insulin and/or Oral Antihyperglycemic Agents in Patients with Type 2 Diabetes Mellitus RONALD M. GOLDENBERG*, MANUEL PUIG-DOMINGO, VIVIAN FONSECA, EDWARD C. WANG, JAY LIN, MELANIE J. DAVIES, FRANCISCO JOSÉ TINAHONES, BERNARD CHARBONNEL Thornhill, ON; Barcelona, Spain; New Orleans, LA; Bridgewater, NJ; Flemington, NJ; Leicester, UK; Málaga, Spain; Nantes, France
Figure 1. A1C improvement with 1.8 mg liraglutide is marginally greater at higher baseline BMI. (a) Pooled analysis of the correlation of change in A1C from baseline vs. baseline BMI for liraglutide 1.8 mg: a crude regression line of the analysis is shown in bold (no modeling done), the model-adjusted slope is 0.011% per kg/m2. (b) Forest plots showing the estimated influence of baseline BMI on change in A1C for liraglutide 1.2 mg, 1.8 mg and placebo. Data are modeled estimates with 95% confidence intervals.
A1C reduction of 0.11%. In conclusion, there was no clinically relevant A1C improvement associated with liraglutide with higher baseline BMI (up to 45 kg/m2).
94 Implementing Standardized Best Practices for Reducing Diabetes Foot Ulcer Risk in a Large Academic Clinic JANINE C. MALCOLM*, SHARON M. BREZ, SHERYL M. IZZI, BRIGITTE SKINNER Ottawa, ON Foot ulcers are a common, often preventable complication of diabetes associated with burdens and costs. Recent reports indicate eastern Ontario has a disproportionately high incidence of lower
Aims: To evaluate the safety and efficacy of lixisenatide in combination with basal insulin oral antihyperglycemic agents in patients with type 2 diabetes mellitus (T2DM). Methods: This was a meta-analysis of 1198 patients from 3 phase III, randomized, placebo-controlled trials from the lixisenatide clinical development program (GetGoal-L, GetGoal-Duo-1 and GetGoal-L-Asia). Results: Mean baseline characteristics: age: 57.2 years; diabetes duration: 11.7 years; body mass index: 30.3 kg/m2; mean A1C was 8.2% for lixisenatide vs. 8.1% for placebo. At endpoint, mean A1C was 7.5% vs. 7.9% for lixisenatide and placebo, respectively. A significantly higher proportion of lixisenatide patients achieved A1C <7% vs. placebo (odds ratio [95% CI]: 3.7 [1.6, 8.2], p¼0.0016). Lixisenatide was more than 3 times more likely than placebo to result in A1C <7% and no weight gain (odds ratio [95% CI]: 3.4 [1.7, 6.8], p¼0.0008), more than 2.5 times more likely than placebo to result in A1C <7% and no documented symptomatic hypoglycemia (odds ratio [95% CI]: 2.7 [1.3, 5.4], p¼0.0073) and more than 2.5 times more likely to result in A1C <7% and no weight gain and no documented symptomatic hypoglycemia (odds ratio [95% CI]: 2.6 [1.5, 4.7], p¼0.0009). Conclusions: In patients with T2DM, lixisenatide in combination with basal insulin antihyperglycemic agents is significantly more effective than placebo in achieving A1C <7%, and is more than 2.5 times more likely to result in A1C <7% with no documented hypoglycemia and no weight gain. Lixisenatide is a treatment option as add on to treatment with basal insulin.