POSTER PRESENTATIONS

328 | CANADIAN JOURNAL OF DIABETES

99 Effect of the GLP-1 Analog Liraglutide on Glycemic Control and Weight Reduction in Patients on Metformin and Rosiglitazone: a Randomized Double-Blind Placebo-Controlled Trial. B. ZINMAN*1, J. GERICH1, J. BUSE1, A. LEWIN1, S. L. SCHWARTZ1, P. RASKIN1, P. M. HALE1, M. ZDRAVKOVIC1, L. BLONDE1, University of Toronto, Canada; Rochester University Medical School, NY; North Carolina University Medical School, Chapel Hill, NC; National Research Institute, Los Angeles, CA; DGD Research, San Antonio, CA; Texas University, Dallas, TX; Novo Nordisk, Princeton, NJ, USA; Bagsvaerd, Denmark; Ochsner Medical Center, New Orleans, LA, USA This 26-week randomized trial compared the efficacy and safety of two doses of liraglutide (lira; 1.2 and 1.8 mg, OD) to placebo (plb) in patients with Type 2 DM on metformin 2 g (met; 1 g, BD) and rosiglitizone 8 mg (rosi; 4 mg, BD). Subjects were previously treated with 1 or more oral antidiabetic drugs (OADs). 533 subjects were randomized (mean age 55.1±10.2 years, mean BMI 33.5±5.2 kg/m2, mean HbA1c 8.3±1.0%). All patients received run-in rosi and met therapy before being randomized to lira or lira plb. Lira 1.2 mg and 1.8 mg reduced HbA1c more than placebo (ANCOVA, p<0.0001) and more of the subjects in the lira groups reached HbA1c 6.5 and 7.0% (p<0.01 vs. placebo). Body weight decreased significantly with lira as compared to placebo (Table). Most common adverse events in the lira groups were GI disorders (mainly nausea) and were generally transient. The rates of minor hypoglycemic episodes (<3.1 mmol/L) were 0.38 and 0.64 events/year for lira 1.2 and 1.8 mg respectively, vs. 0.17 events/year for plb (p=0.0968 and 0.0040, respectively). No subjects reported severe hypoglycemic events. Lira added to met + rosi was generally well tolerated and significantly improved glycemic control, and reduced body weight in comparison to plb + met + rosi therapy with low rates of hypoglycemia. Lira 1.2 mg+

met + rosi N=178

Lira1.8 mg + met + rosi N=178

Plb + met + rosi N=177

Final HbA1c, % (SD) Change HbA1c,%

7.0 (1.1) -1.48*

7.1 (1.1) -1.48*

7.9 (1.3) -0.54

% HbA1c <7.0% 58* 54* 28 % HbA1c 6.5% 36* 37* 14 Weight change, kg (SE) -1.02 (0.33)* -2.02 (0.32) 0.60 (0.34) Final FPG, mmol/L (SD) Change FPG, mmol/L

7.7 (2.6) -2.2*

7.6 (2.3) -2.4*

9.5 (3.1) -0.4

Change PPG, mmol/L -2.6 -2.7* -0.8 % reporting minor hypo events/subject/year

9 0.38

8 0.64*

5 0.17

*p<0.05 vs. placebo. FPG, fasting plasma glucose; PPG, post-prandial glucose

ABSTRACT #54

C&SS

GUT HORMONES

101

Significantly Better Glycemic Control and Weight Reduction with Liraglutide, a Once-daily Human GLP-1 Analog, Compared with Insulin Glargine: All as Add-on to Metformin and a Sulfonylurea in Type 2 Diabetes. O. SCHMITZ*1, D. RUSSELL-JONES1, A. VAAG1, B. K. SETHI1, N. LALIC1, S. ANTIC1, M. ZDRAVKOVIC1, G. M. RAVN1, R. SIMÓ1, University, Aarhus, Denmark; Royal Surrey County Hospital, Guildford, UK; Steno Diabetes Center, Gentofte, Denmark; Care Hospitals, Hyderabad, India; University, Belgrade; Diabetes & Metabolic Diseases Clinic, Niš, Serbia; Novo Nordisk, Bagsvaerd, Denmark, Vall d’Hebron University Hospital, Barcelona, Spain A 26-week, randomized trial compared the efficacy and safety of liraglutide (lira; 1.8 mg, QD), lira placebo (plb) and open label insulin glargine (glar), all as add-on to metformin (met; 1 mg, BID) and glimepiride (glim; 2–4 mg QD). 581 subjects were randomized (mean age 57.5±9.9; mean BMI 30.5±5.3 kg/m2, mean HbA1c 8.2±0.9 %). Lira+met+glim reduced HbA1c more than glarg and plb in combination with met and glim (ANCOVA, p=0.0015; p<0.0001) and more of the subjects in the lira group reached HbA1c 6.5% (p<0.0001). Estimated weight difference between lira and glar groups was -3.4 kg (p<0.0001) and -1.4 kg between lira and plb groups (p=0.0001). Glar was individually titrated according to a patient-driven algorithm, and the average dose of glar was 24 IU/day at end of trial. Most common AEs in the lira group were GI disorders (mainly nausea). Nausea occurred in ~15% of subjects in the lira group, but was transient. Frequency of minor hypoglycemic episodes (<56 mg/dL) were similar for the lira and glar groups and more frequent than in the plb group. Five subjects reported major hypoglycemic events in the lira group (only one required medical assistance; none resulted in coma or seizure). Presence of lira antibodies was 9.8%. Lira + met and a sulfonylurea (SU) was generally well tolerated and statistically significantly improved glycemic control, and reduced body weight in comparison to met and an SU alone and to glar added to met and an SU. lira1.8+met+glim plb+met+glim glar+met+glim Final HbA1c, % (SE) Change HbA1c, % (SE)

7.0 (1.0) -1.33 (0.09)*^

8.1 (1.3) -0.24 (0.11)

7.2 (0.9) -1.09 (0.09)

% HbA1c 6.5% 37.1*^ 10.9 23.6 Weight change, kg (SE) -1.81 (0.33)*^ -0.42 (0.39) 1.62 (0.33) Final FPG, mg/dL (SE) Change FPG, mg/dL

137.7 (39.3) -27.92*

180.2 (51.4) 9.56

133.2 (38.1) -32.16

% reporting minor hypo events 27.4 16.7 28.9 % reporting nausea 13.9 3.5 1.3 Week 26 FPG titration targets reached: 100 mg/dL (% subjects) 120 mg/dL (% subjects)

47 (20.26) 93 (40.09)

*Statistically significant compared to: *met+glim; ^glar+met+glim

102

A systematic review of the effect of oral antidiabetic agents on A1C levels. DIANA SHERIFALI1, KARA NERENBERG1, HERTZEL GERSTEIN1, Department of Medicine, McMaster University, Hamilton, Ontario. Background:Treatment of individuals with type 2 diabetes often requires the addition of single or multiple oral antidiabetic (OAD) agents to lifestyle modification to optimally manage glycemic control. The choice of OAD agents depends on the patient, specific therapeutic indications, adverse effects and the anticipated improvement in A1C. To date, the majority of the published trials of OAD effectiveness used to guide clinical decision-making are of poor methodological quality. Study Objective and Methods: The purpose of this review is to systematically identify randomized double-blind, placebo-controlled trials of adequate methodologic quality that assessed the effectiveness of currently available OAD agents to reduce A1C levels in non-pregnant adult individuals with type 2 diabetes. Eligible studies must also meet the following criteria: published in English, peer-reviewed journals; sample size of at least 50 participants in each study arm; duration of at least 12 weeks; and had at least 70% follow up in each arm at 12 weeks. Results:A comprehensive literature search of three electronic databases (Cochrane, Embase and Medline) from January 1980 to March 2007 identified 4319 citations. Eligibility screening was completed in two steps: title and abstract, then full text review. In total, 83 of 4319 (1.9%) citations met the eligibility criteria for the meta-analysis. Planned data analyses include the proportional decrease in A1C from baseline compared to placebo by specific OAD agent. Additional analyses will determine the effect of age, sex, ethnicity, background therapy and OAD agent dose on the changes in A1C. Discussion:The preliminary results of this rigorous systematic review highlights that the majority of published OAD agent trials are of sub-optimal methodological quality. Meta analysis (in progress) of data from 1.9% of the included trials will provide clinicians with evidence-based information of the effectiveness of different OAD agents.

ABSTRACT #196

C&SS

CLINICAL CARE

Significantly Better Glycemic Control and Weight Reduction with Liraglutide, a Once-Daily Human GLP-1 Analog, Compared With Glimepiride: All as Monotherapy In Type 2 Diabetes. A. GARBER*1, R. HENRY1, R. RATNER1, P. GARCIA-HERNANDEZ1, H. M. RODRIQUEZ PATTZI1, I. OLVERA-ALVAREZ1, P. M. HALE1, M. ZDRAVKOVIC1, B. BODE1, Baylor College of Medicine, Houston, TX; University of California University , San Diego, CA; MedStar Research Institute, Hyattsville, MD, USA; University Hospital, Monterrey; Private Practice, Mexico City, Mexico; Novo Nordisk, Princeton, NJ, USA; Novo Nordisk, Bagsvaerd, Denmark; Atlanta Diabetes Associates, Atlanta, GA, USA A 52-week randomized trial compared the efficacy and safety of two doses of liraglutide (lira; 1.2 and 1.8 mg, OD) to glimepiride (glim; 8 mg OD). Subjects were previously treated with diet and exercise (D/E) or previous OAD monotherapy (mono). 746 subjects were randomized (mean age 53.0±10.9; mean BMI 33.1±5.8 kg/m2, mean HbA1c 8.3±1.1%). Lira 1.2 and 1.8 mg reduced HbA1c more than glim (ANCOVA, p=0.0014; p<0.0001) and more of the subjects in the lira groups reached HbA1c 6.5 and <7.0% (p<0.01 vs. glim). In addition, the decrease in HbA1c with lira 1.8 mg was significantly greater than the decrease with lira 1.2 mg (p=0.0046). At end of study, there was significant weight decrease in the lira groups, compared to weight gain in the glim group. The most common adverse events in the lira groups were GI disorders (mainly nausea). Nausea occurred in ~29% of subjects in the lira groups, but was transient. The rates of minor hypoglycemic episodes (<3.1 mmol/L) were significantly lower for the lira groups, vs. glim. No subjects reported major hypoglycemic events. Lira monotherapy significantly lowered HbA1c versus glim and, at the same time, resulted in weight loss and lower rates of hypoglycemia. Liraglutide

1.2 mg, N=251 Liraglutide 1.8 mg, N=247

Glimepiride N=248

Final HbA1c, % (SD) Change HbA1c, all % Change HbA1c, from D/E % Change HbA1c, mono %

7.5 (1.3) -0.84* -1.19 -0.47*

7.2 (1.2) -1.14*† -1.60*† -0.71*†

7.8 (1.2) -0.51 -0.88 -0.17

% HbA1c <7.0% 43* 51* 28 % HbA1c 6.5% 28* 38* 16 Weight change, kg (SE) -2.05 (0.28)* -2.45 (0.28)* 1.12 (0.27) Final FPG, mmol/L (SD) Change FPG, mmol/L

8.6 (3.1) -0.8*

8.3 (2.7) -1.42*†

9.3 (3) -0.3

Change PPG, mmol/L -1.7 -2.1* -1.4 % reporting minor hypo events/subject/year

12 0.30*

8 0.25*

24 1.96

% reporting nausea 27.5 29.3 8.5 *p<0.05 vs. glimepiride; †p<0.05 1.8 mg vs. 1.2 mg. FPG, fasting plasma glucose; PPG, post-prandial glucose

ABSTRACT #32

C&SS

GUT HORMONES

103