Taspoglutide Abstracts 2010 American Diabetes Association Meeting                 

                                                                                                                                                

Once Weekly Taspoglutide, a Human GLP-1 Analog, Is Superior to Sitagliptin in Improving Glycemic Control and Weight Loss in Patients with Type 2 Diabetes (T2D): Results from the T-emerge 4 Trial

Abstract No: 0058-OR RICHARD BERGENSTAL, ADRIANA FORTI, JEAN-LOUIS CHIASSON, MIKE WOLOSCHAK, MARK BOLDRIN, LAWRENCE A. LEITER, RAFFAELLA BALENA

Minneapolis, MN, Fortaleza, Brazil, Montreal, QC, Canada, Nutley, NJ, Toronto, ON, Canada, Basel, Switzerland

Abstract Body:

This trial compared taspoglutide, a once-weekly human GLP-1 analog undergoing Phase 3 clinical trials, with sitagliptin and placebo in patients (pts) with T2DM inadequately controlled on metformin. In this double-dummy, 24-wk study, 666 adult pts with an A1c between 7%-10% were randomized (2:2:2:1) to subcutaneous taspoglutide 10 mg weekly (Taspo10), taspoglutide 10 mg weekly for 4 wks titrated to 20 mg weekly (Taspo20), sitagliptin 100 mg QD orally (SIT), or placebo (P). Baseline characteristics were similar across the groups; average age was 56 yrs, A1c 8.0%, body mass index 32 kg/m2, and duration of T2DM 6 yrs. Taspo10 and Taspo20 significantly reduced A1c (Fig 1), body weight (Fig 2), and FPG (-38.9, -42.1, -24.3, and -1.3 mg/dL, respectively) compared with SIT and P, and Taspo10 and Taspo20 were superior to SIT. Target A1c of ≤7% was achieved by 68%, 72%, 55%, and 18% of pts receiving Taspo10, Taspo20, SIT, and P, respectively. Gastrointestinal (GI) complaints were the most frequent adverse events and were reported in more pts receiving Taspo than SIT. GI events with Taspo were mostly mild and moderate in severity and transient in most pts, but were cause for withdrawal in 14%, 10%, 0.5%, and 1% of pts on Taspo10, Taspo20, SIT, and P, respectively. In conclusion, once-weekly Taspo provided superior glycemic

                                                        

Taspoglutide, a Once-Weekly Human GLP-1 Analog, Provides Comparable Glycemic Control to Insulin Glargine, with Superior Weight Loss and Less Hypoglycemia in Type 2 Diabetes (T2D): A Phase 3, Open-Label Trial (T-emerge 5)

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0060-OR  Oral 

Author(s): MICHAEL NAUCK, EDWARD HORTON, MIRJANA ANDJELKOVIC, F. JAVIER AMPUDIA-BLASCO, MARK N. BOLDRIN, RAFFAELLA BALENA

Bad Lauterberg im Harz, Germany, Boston, MA, Basel, Switzerland, Valencia, Spain, Nutley, NJ

Abstract Body:

Taspoglutide is a once-weekly (QW) human GLP-1 analog in Phase 3 development.T-emerge 5 compared taspoglutide to insulin glargine (INS) once daily (QD) in adult insulin-naïve patients (pts) with T2D inadequately controlled with metformin (MET) plus sulfonylurea (SU). After discontinuation of SU, 1049 pts were randomized 1:1:1 to QW taspoglutide 10 mg (Taspo10), or 10 mg for weeks 1-4 then 20 mg (Taspo20), or INS QD for 24 weeks. INS was titrated using a forced titration algorithm to achieve optimal target fasting plasma glucose of 110 mg/dL (6.1 mmol/L). The primary glycemic efficacy analysis was applied to the intent-to-treat population to test the non-inferiority of glycemic control (A1c) with Taspo10 and Taspo20 vs INS. Baseline characteristics were comparable across groups (mean age 58 yrs, BMI 32 kg/m2, body weight 91 kg, and A1c 8.3%). A1c change from baseline was -0.8%, -1.1% and -0.8% for Taspo10, Taspo20 and INS groups, respectively, with bothTaspo10 and Taspo20 non-inferior to INS (P=0.30 and 0.08 for T10 and T20) and greater proportions of patients achieving A1c ≤7.0% (Taspo10, 39%; Taspo20, 47%; INS, 32%). Taspo10 and Taspo20 produced significantly greater weight loss vs. INS (Figure). Hypoglycemia (confirmed/unconfirmed) was lower with Taspo10 (5%) and Taspo20 (6%) vs. INS (18%). Withdrawals due to adverse events (AEs) were higher with Taspo vs. INS, primarily due to gastrointestinal (GI) AEs (Taspo10, 5%; Taspo20, 9%; INS, 0). Serious AE incidence was similar among groups. In summary, the addition of once-weekly Taspo vs. daily INS to MET in pts failing on MET+SU produced comparable glycemic control

Superior Glycemic Control with Taspoglutide, a Once-Weekly Human GLP-1 Analog, Compared with Twice Daily Exenatide in Type 2 Diabetes (T2DM) Inadequately Controlled on Oral Agents: The T-emerge 2 Trial

Abstract No: 0062-OR 

Author(s): JULIO ROSENSTOCK, BOGDAN BALAS, BERNARD CHARBONNEL, GEREMIA B. BOLLI, MARK BOLDRIN, ROBERT RATNER, RAFFAELLA BALENA

 

Dallas, TX, Basel, Switzerland, Nantes, France, Perugia, Italy, Nutley, NJ, Hyattsville, MD

Abstract Body:

Taspoglutide is a once-weekly (QW) human GLP-1 analog in Phase 3 development. T-emerge 2 compared the safety and efficacy of taspoglutide (Taspo) vs exenatide (Exe) in patients with T2DM inadequately controlled with metformin+/-thiazolidinedione. In this open-label study, 1149 subjects were randomized to subcutaneous Taspo 10 mg QW (Taspo10), Taspo 10 mg for 4 wks titrated to 20 mg QW (Taspo20), or Exe 5 mcg BID for 4 wks titrated to 10 mcg BID. Primary outcome was A1c change at wk 24, testing for noninferiority (NI) vs Exe (lower limit of 2-sided 95% CI for A1c difference ≤0.4%). If NI was demonstrated, then superiority was tested under closed test procedure, limit of 0. Baseline characteristics (56 yr, 6.5 yr T2DM, A1c 8.1%, BMI 33 kg/m2) were similar across groups. At 24 wks, reductions in A1c and FPG with Taspo10 and Taspo20 were superior to Exe (Table). More patients on Taspo10 or Taspo20 achieved target A1c ≤7% than Exe: 65%, 68%, and 52%; respectively. Dose-dependent weight loss was seen with Taspo and weight loss with Taspo20 was similar to Exe (Table). Gastrointestinal (GI) complaints were the most frequent adverse events. Although they occurred with a higher incidence in the Taspo groups, discontinuation rate due to GI events was similar in the 3 arms. In conclusion, once-weekly Taspo provided superior glycemic control to Exe, with similar body weight reductio

n at the higher dose and comparable tolerability.[table1]

LSMean ± SE	T10 n=384	T20 n=392	E n=373
Baseline A1c (%)	8.1±0.1	8.1±0.1	8.0±0.1
? baseline A1c	-1.2±0.1	-1.3±0.1	-1.0±0.1
95% CI	-1.4, -1.1	-1.5, -1.1	-1.1, -0.8
Diff from E	-0.3±0.1**	-0.3±0.1**	—
24 Week A1c%	6.9±0.1	6.8±0.1	7.2±0.1
Baseline FPG (mg/dL)	179±2.4	177±2.3	178±2.4
? baseline FPG	-39±3.6	-45±3.6	-33±3.5
95% CI	-46, -32	-52, -38	-39, -26
Diff from E	-6.7±2.4*	-12.1±2.4**	—
Baseline body weight (kg)	95.5±1.0	93.2±1.0	94.5±1.0
? baseline body weight	-1.6±0.4	-2.3±0.4	-2.3±0.4
95% CI	-2.3, -0.9	-3.1, -1.6	-3.0, -1.6
Diff from E	0.7±0.3*	-0.05±0.3	—
*P<0.05; **P<0.0001

 

                                                                        

 

 

 

 

 

Taspoglutide, a Once-Weekly Human GLP-1 Analog, as Monotherapy Significantly Lowers A1c and Body Weight in Patients with Type 2 Diabetes (T2D): Results from the T-Emerge 1 Phase 3 Trial

Abstract No: 0399-PP  Abstract Type: Presidents Poster 

Author(s):

ITAMAR RAZ, VIVIAN FONSECA, MARK KIPNES, LAURENCE DURRWELL, JOHN HOEKSTRA, MARK BOLDRIN, RAFFAELLA BALENA

Jerusalem, Israel, New Orleans, LA, San Antonio, TX, Basel, Switzerland, Richmond, VA, Nutley, NJ

Abstract Body:

Taspoglutide is a once-weekly human GLP-1 analog in Phase 3 clinical trials for T2D. This was a randomized, double-blind, placebo-controlled trial of taspoglutide monotherapy in drug-naïve patients. Adults (n=373) uncontrolled on diet and exercise with A1c ≥6.5% and ≤10% were randomized to subcutaneous taspoglutide 10 mg weekly (Taspo10), taspoglutide 20 mg weekly (Taspo20; after 4 weeks of Taspo10), or placebo (PL) for 24 weeks. Patient demographics were similar among the groups; ∼64% were women, mean age 54 yrs, body mass index 32 kg/m2, mean A1c was 7.6% and duration of T2D ∼3 yrs. Primary efficacy results at week 24 in the intent-to-treat population (LOCF) are shown in the Table. Reductions from baseline in A1c and FPG were significantly greater with Taspo10 and Taspo20 than with PL. Target A1c of ≤7% was achieved by 80%, 83%, and 42% in the Taspo10, Taspo20, and PL groups, respectively. Reduction in body weight in the Taspo20 group was significantly greater than in PL (Table). The most frequently reported adverse events were nausea and vomiting, occurring at a greater incidence in the Taspo10 and Taspo20 groups than PL. Withdrawals due to gastrointestinal adverse events occurred in 5.2%, 7.8% and 0.8% of patients in the Taspo10, Taspo20, and PL groups, respectively. In conclusion, once-weekly

taspoglutide as monotherapy in drug-naive patients with low baseline A1c, significantly improved glycemic control, reduced body weight, and was well tolerated.[table1]

LSMean ± SE	T10 n=112	T20 n=127	PL n=115
Baseline A1c (%)	7.5±0.1	7.7±0.1	7.6±0.1
? baseline A1c (95% CI)	-1.0±0.1 (-1.1, -0.9)	-1.2±0.1 (-1.3, -1.1)	-0.1±0.1 (-0.2, 0.04)
Diff from PL	-0.9±0.1**	-1.1±0.1**	—
Baseline FPG (mmol/l)	8.8±0.2	9.0±0.2	8.6±0.2
? baseline FPG (95% CI)	-1.6±0.2 (-1.9, -1.2)	-1.9±0.2 (-2.2, -1.6)	-0.1±0.2 (-0.4, 0.3)
Diff from PL	-1.5±0.2**	-1.8±0.2**	—
Baseline body weight (kg)	88.4±1.7	85.0±1.6	87.4±1.7
? baseline body weight (95% CI)	-1.5±0.3 (-2.1, -0.8)	-2.2±0.3 (-2.8, -1.7)	-1.2±0.3 (-1.8, -0.6)
Diff from PL	-0.2±0.4	-1.0±0.4*	—
*P<0.05; **P<0.0001

 

Once-Weekly Taspoglutide, a Human GLP-1 Analog, Is Superior to Placebo in Improving Glycemic Control and Body Weight Loss in Obese Patients with Type 2 Diabetes (T2D) Inadequately Controlled with Metformin Monotherapy: Results from the T-emerge 7 Trial

 

Abstract No: 0585-P 

PRISCILLA HOLLANDER, MONICA BENGUS, ANTHONY BARNETT, BEN LASKO, MARK BOLDRIN, RAFFAELLA BALENA, F. XAVIER PI-SUNYER

Dallas, TX, Basel, Switzerland, Birmingham, United Kingdom, Toronto, ON, Canada, Nutley, NJ, New York, NY

Taspoglutide, a once-weekly human GLP-1 analog, is undergoing Phase 3 clinical trials for T2D. The primary objective of this trial was to assess the efficacy of taspoglutide compared with placebo on glycemic control (assessed by A1c) after 24 weeks of treatment in obese patients (pts) with T2D inadequately controlled with metformin. In this randomized, double-blind study, 305 adult pts with an A1c between 6.5%–9.5% were randomized (1:1) to subcutaneous taspoglutide 20 mg weekly (Taspo20) (after 4 weeks of taspo 10 mg weekly) or placebo (PL). Baseline characteristics were similar across groups: the approximate age was 54 yrs, body mass index was 37 kg/m2 (22% with BMI>40 kg/m2), body weight was 103 kg, and pts had T2D for 5.1 yrs. At 24 weeks, reductions in A1c and FPG with Taspo20 were statistically superior to that with PL (Table). More pts in Taspo20 group achieved target A1c of ≤7.0%: 72.5% and 36.4% in the Taspo20 and PL groups, respectively. Rescue medication was required in 12.6% and 3.4% of pts in PL and Taspo20 groups, respectively. Weight loss with Taspo20 was superior to PL (Table). Gastrointestinal complaints were the most frequent adverse events, were reported in more pts receiving Taspo20 vs. placebo, and led to withdrawal in 3.9% and 1.3% of pts in the Taspo20 and PL groups, respectively. In conclusion, once-weekly taspoglutide 20 mg provided superior glycemic control and weight loss compared with placebo in obese pts with T2D inadequately controlled by metformin.[table1]

LSMean ± SE (ITT Population)	PL N=143	Taspo20 N=149
Baseline A1c (%)	7.6±0.1	7.5±0.1
? baseline A1c	-0.1±0.1	-0.8±0.1
95% Confidence Interval (CI)	-0.2, 0.0	-0.9, -0.7
Diff from PL		-0.7±0.1**
Baseline FPG (mmol/l)	8.8±0.2	9.1±0.2
? baseline FPG	0.0±0.2	-1.3±0.2
95% CI	-0.4, 0.4	-1.7, -1.0
Diff from PL		-1.3±0.3**
Baseline body weight (kg)	101.4±1.5	103.6±1.5
? baseline body weight	-1.9±0.3	-3.2±0.3
95% CI	-2.5, -1.3	-3.8, -2.6
Diff from PL		-1.3±0.4*
*P<0.05; **P<0.0001