JUNE 2005 VOLUME 54 SUPPLEMENT 1
`
`ABSTRACT BOOK
`65th Scientific Sessions
`Friday, June 10-Tuesday, June 14, 2005
`
`The San Diego Convention Center
`San Diego, California
`
`2004-2005 Officers and Board of Directors
`
`Past Officers
`
`Banting Medal for Scientific Achievement
`
`Outstanding Scientific Achievement Award
`
`Previous National Achievement Award Recipients
`
`2004-2005 Professional Section Council Chairs
`
`2004-2005 Research Awards and Grants
`
`2004-2005 Scientific Sessions Planning Committee
`
`2004-2005 Abstract Reviewers
`
`General Information
`
`ADA Celebration
`
`Corporate-Sponsored Symposia
`
`Scientific Sessions Day-At-A-Glance
`
`Oral and Poster Discussion Presentations
`
`Commercial Exhibits
`
`Abstracts
`
`Subject Index
`
`Abstract Author Index
`
`Duality of Interest Information
`
`vw.di abetes.o~gfilia betes
`
`SCIENTIFIC
`65th SESSIONS
`
`Juno 10· 1<1, 2005 · Son Diego, Col1lomio
`
`'Uh!v. or Minn.
`Om-Medical
`LibPaPy
`06 02 05
`
`®
`~EAZ 54 Suppl ement ( I) 1- A880 (2005)
`::>N 001 2- 1797
`
`1
`
`4
`
`6
`
`7
`
`8
`
`10
`
`11
`
`17
`
`17
`
`19
`
`20
`
`23
`
`33
`
`38
`
`67
`
`A1
`
`A685
`
`A723
`
`A787
`
`MYLAN Ex. 1007, Page 1
`
`

`
`MULTIPLE AGENT THERAPY FOR TYPE 2 DIABETES
`
`11-0R
`Effect of Adding MK-0431 to On-Going Metformin Therapy in
`Type 2 Diabetic Patients Who Have Inadequate Glycemic Control
`on Metformin
`RONALD BRAZG, KAREN THOMAS, PENG ZHAO, LEI XU, XUN
`CHEN, PETER STEIN. Renton, WA; Rahway, NJ
`MK-0431 , an oral, potent, and selective DPP-lV inhibitor is currently in
`development for treatment of type 2 diabetes (T2D). Metformin is a com(cid:173)
`monly used first-line antihyperglycemic agent. Combination treatment with
`MK-0431 and metforrnin may be useful since these agents target different
`pathophysiolic processes leading to hyperglycemia in T2D. Patients {pts)
`with T2D and inadequate glycemic control on metfonnin monotherapy (on
`a stable dose of <: l500 mgld for :2:6 wks) were recruited for a double-blind,
`randomized, placebo (Pbo )-controlled, 2-period crossover study. After a 5-
`wk screening/diet run-in period, 28 pts (base line A 1 C range: 6.5-9.6%)
`receiving metformin were randomized into of 1 of2 treatment sequences:
`adding Pbo for 4 wks followed by adding MK-0431 50 mg b.i.d. for 4 wks,
`or vice versa. At the end of each period, pts were domiciled for 24 hrs at
`the investigational site for frequent blood sampling. Resu lts from Period 2
`showed that pts who had received MK-0431 in Period 1 did not return to their
`pre-treatment baseline level at the end of the 4-wk Pbo treatment in Period
`2, suggesting a substantial carryover effect. Because of the carryover effect,
`Period 1 results may provide a better estimate of treatment effect, and hence
`are the focus of this report (Table). No weight gain, increases in Gl adverse
`events or hypoglycemia events were observed. In this study, the combination
`of MK-0431 and metfonnin was efficacious and generally well-tolerated
`as a treatment regimen for pts with T2D.
`Parameter
`Metformin + Metformin + Difference
`Placebo
`MK-0431
`in LS
`50 mg b.i.d.
`means
`< 0.001
`125.0
`-32.9
`157.9
`24-hrWMG (mgldl)
`< 0.001
`-23.8
`·-20.3
`-3.4
`Change in FPG (mgldl)
`0.003
`-28.7
`-33.7
`5.0
`Change in fructosamine (mmol/1)
`0.046
`-23.1
`-28.0
`4.9
`Change in MDG (mg/dl)
`Group data are LS means or mean change from baseline; WMG -weighted
`mean glucose; MDG = mean daily glucose calculated as the mean of 7-
`point fingerstick glucose determinations
`
`P l'aiue
`
`MULTIPLE AGENT THERAPY FOR
`TYPE 2 DIABETES
`
`9-0R
`Comparison of Exenatide and Insulin Glargine in MET and SU(cid:173)
`Treated Patients with Type 2 Diabetes: Exenatide Achieved Equiv(cid:173)
`alent Glycemic Control, with Weight Reduction and Less Noctur(cid:173)
`nal Hypoglycemia
`ROBERT J. HEINE, LUC F. VAN GAAL, DON JOHNS, MICHAEL
`J. MIHM, MARIO H. WIDEL, ROBERT G. BRODOWS. Amsterdam,
`Netherlands; Antwerp, Belgium; Indianapolis, IN
`Clinical studies have shown that exenatide improves glycemic control with
`a low incidence of hypoglycemia and the absence of weight gain in patients
`wit h type 2 diabetes inadequately controlled by MET and/or SU. The addi(cid:173)
`tion of basa l insulin is common practice when orals fail, but is complicated
`by increased hypoglycem ia and weight gain. This 26-week, multi-center,
`phase 3 trial was designed to detem1ine if exenatide can be used safely and
`effectively as an alternative to basal insulin glargine. Patients were ran(cid:173)
`domi zed to exenatide (5!-lg BfD for first 4 wks, I 01-1g BID for remainder of
`study, n=283) or glargine QD {n=268), adj unctive to pre-existing MET+SU.
`Baseline A 1 C were 8.2±1.0% and 8.3±1.0%, respectively. At endpoint, exe(cid:173)
`natide and glargine achieved similar A IC reductions (- 1.0±0.1% vs
`-1.1 ±0.1 %, respectively; 95% Cl for exenatide- glargine difference was-
`0.1 to 0.2%) and percent of patients to A 1 C:S7% (48% vs 46%). Weight
`change was -2.3±0.2kg for exenatide, + 1.8±0.2kg for glargine {p<O.OO 1 ). As
`measured by 7 -point glucose monitoring, exenatide reduced postprandial
`excursions following breakfast and dinner, whi le glargine predominantly
`reduced fasting glucose ( -1 .2±0.2 vs -2.9±0.2mmol/L, p<O.OO I). Exenatide
`reduced glucose excursions following a test meal, but glargine did not reduce
`post-meal excursions (incremental glucoseAUC04h" = -0.3±1.0mmol-hr/L,
`n=4 1 vs 7.0± 1.2mmol-hr/L, n=37, p<O.OOI). The most common adverse
`event for exenatide was nausea (57%), which was geneni lly mild-to-mod(cid:173)
`erate (6% discontinuation due to nausea) with decreasing incidence during
`the study. Rates of symptomatic hypoglycemia were similar between treat(cid:173)
`ments, but nocturnal hypoglycemia was lower for exenatide (0. 9±0.4 vs
`2.4±0.4 mean events/patient year, p<O.OO I). Exenatide has potential as an
`alternative to insulin glargine in the management of type 2 diabetes sub-opti(cid:173)
`mally contro lled on MET+SU.
`
`10-0R
`Effects ofDAC-GLP: I (CJC-1131) on Glycemic Control and Weight
`over 12 Weeks in Metformin-Treated Patients with Type 2 Diabetes
`ROBERT E. RATNER, POL-HENRI GUIVARC'H, JEAN-FRAN<;:OIS
`DREYFUS, J EAN-PAUL CASTAIGNE, DANIEL J. DRUCKER,
`JEAN-PIERRE HALLE, STUART A. ROSS , MARK S. KIPNES.
`Bethesda, MD; Montreal, QC, Canada; Toronto, ON, Canada; San
`Antonio, TX; Calgmy, AL, Canada
`CJC-1131 is a GLP-1 analogue binding covalently to albumin in vivo, with
`a 10-day half-life in man. This study assessed the effects ofCJC-1131 on
`. glycemic control in patients (PT) with type 2 diabetes inadequately controlled
`with their current dose ( 1.5-2.25 g) of metformin (MET) alone or with sul(cid:173)
`fonylurea (SFU). The 12-wk investigation was a randomized, double-blind,
`placebo (PBO)-controlled multicenter study.
`After a 4-wk baseline period and washout for those on SFU, 81 PT,
`51 M/30F, age 56±8.8 yr (mean±SD), BW 92.5±18.05 kg, BMl 32.0±4.49
`kglm\ HbA 1 c 7.9±0.83 %, FPG 9.5±2.61 mmol/L, were randomized to CJC-
`1131 low (LD) or high (HD) dose or matching PBO. PT on SFU {n=40)
`were washed out and equally allocated to each arm. All subjects continued
`MET with unchanged doses. Weekly visits during the 1" month allowed CJC-
`1131 dose adjustment. The average daily do~e was 2. 1 ±1.06 J.lglkg (LD) &
`2.6±0.97 J.lg/kg (HD).
`In the 57 PT evaluated for efficacy, the mean difference from PBO (mean
`± SEM) for HbA 1 c changes from baseline was -1 .1 ±0.23% (p<O.OOO 1) (HD)
`& -0.6 ±0.25 % (p<0.03) (LD); 58 % of HD patients with baseline
`HbA 1 c> 7.0% achieved HI? A 1 cs 7.0 %; FPG was significantly reduced in the
`HD & LD anns compared to PBO (p<0.02 & p<0.04 respectively). Body
`weight was reduced in the 3 arms, more with CJC-113 1: -2.5±2.18 kg
`(mean±SD) than PBO:: 1.6±1.59 kg (p<0.05). The most frequent AEs were
`GI intolerance mostly during the first 4 wk: moderate nausea was reported
`at least once by·l3 PT and severe nausea once by 1 PT (overall incidence
`25%); 6 PT reported moderate nausea .during the next 4 wk and 1 during
`the last 4 wk of treatment. There were no signs of local intolerance or
`immunogenicity. In conclusion, CJC-1131 in combination with MET sig(cid:173)
`nificantly reduced HbA 1 c without increasing the risk of hypoglycemia, in
`PT previously inadequately treated with MET or MET+SFU.
`
`12-0R
`Low Dose Rosiglitazone Significantly Improves Glycemic Control
`without Increasing Adverse Events in Patients with T2DM Not Well
`Controlled on Insulin
`PRISCILLA HOLLANDER, WAYDE M . WESTON, CHUN HUANG,
`HUBERT CHOU, LISA E. PORTER. Houston, TX; KingofPrussia, PA;
`San Diego, CA
`Insulin-using T2DM patients generally exhibit substantial insulin resistance.
`The addition of insulin sensitizers may complement exogenous insulin to opti(cid:173)
`mize glycemic control. In this 24-wk trial, subjects with inadequate glycemic
`control on INS alone were randomized to double-blind treatment with the
`addition of RSG 2mg od (n=209), RSG 2mg bd (n=209) or placebo (n=212) .
`INS+PBO
`INS+RSG
`lNS+RSG
`HbA1, (mean±SD)
`(liT subjects)
`N=l86
`2mg od
`2mg bd
`N=193
`N=l89
`8.9±1.1
`9.0±1.2
`8.3±1.3
`8.2±1.3
`-0.64±1.[1
`-0.78±l.JI
`·0.381
`80(4U)
`
`Baseline
`Wk24
`Change from Baseline
`Comparison to INS+PBO
`Subjects with reduction from
`baseline ~0.7% (nl%1)
`Comparison to lNS+PBO (95%Cl)
`
`9. 1±1.3
`8.7±1.4
`-0.44±1.2 1
`-0.261
`73 (39.5)
`
`1.99 (·8.00, 11:98)
`
`15.33 (5.27,25.38)
`
`103
`
`(54.8)
`
`lNS+PBO
`N=212
`
`87 (41.0}
`47 (22.2)
`I (0.5)
`23 (10.9)
`3(14)
`
`lNS+RSG
`2mgod
`N=209
`95 (45.5)
`63 (30.1)
`2 (1.0)
`12 (5.7}
`4 (1.4)
`
`lNS+RSG
`2mgbd
`N=109
`94 (45.0}
`57 (27.3)
`0
`23 (11.0)
`2 (1.0)
`
`Subjects reporting hypoglycemia (nl%1)
`Confirmed (BG<50mgldL)
`Withdrawals
`Total edema and edema-related AEs
`Withdrawals
`1p<0.05
`INS+RSG treatment significantly reduced HbA 1, relative to baseline and
`to INS alone. C-reactive protein levels showed statistically significant, dose(cid:173)
`ordered reductions from baseline in JNS+RSG-treated subj ects ( -22.0% and
`-34.2%, p<0.05), and a small, nonsignificant increase in lNS+PBO-treated
`subjects {+2.4%). Repm1s of hypoglycemia (total and confirmed by blood
`glucose measurement) were similar between subjects receiving INS alone
`
`For author duality of interest information, see page A787.
`
`A3
`
`MYLAN Ex. 1007, Page 2