Of 373 randomized patients, 368 received at least one dose of study medication and had at least one follow-up safety measurement, and 354 received at least one dose of study medication and had an evaluable baseline and at least one postbaseline measurement of HbA1c
(Supplementary Fig. 1
). Treatment groups were well matched at baseline, and mean duration of diabetes was 2.1−2.8 years (Supplementary Table 2
Least squares mean HbA1c
decreased from baseline by −0.09 ± 0.07, −1.01 ± 0.07, and −1.18 ± 0.06% with placebo, taspoglutide 10 mg, and taspoglutide 20 mg, respectively (both P
< 0.0001 vs. placebo). Reductions were greater with taspoglutide (10- and 20-mg groups, respectively) in patients with HbA1c
≥8% (–1.69 and –1.72%) vs. <8% (–0.69 and –0.93%) at baseline. A greater proportion of patients in the taspoglutide 10- and 20-mg groups, respectively, achieved HbA1c
of ≤6.5% (60 and 66%) and ≤7.0% (80 and 83%) versus placebo (17 and 40%) (Supplementary Fig. 2A and B
Least squares mean changes from baseline in FPG were –0.08 ± 0.17, –1.55 ± 0.17, and –1.90 ± 0.16 mmol/L with placebo, taspoglutide 10-mg, and 20-mg groups, respectively (both P < 0.001 vs. placebo). Weight loss occurred progressively in all groups and was greater in the taspoglutide 20-mg group versus placebo (–2.25 ± 0.30 kg; P = 0.02).
Significant improvements in HOMA-B were seen with both doses of taspoglutide versus placebo (59 and 65 vs. 2; P
= 0.01 and P
< 0.01 for taspoglutide 10 mg and 20 mg, respectively). Proinsulin-to-insulin ratios significantly decreased with taspoglutide 10 and 20 mg versus placebo (Supplementary Table 3
Treatment-emergent AEs were reported in 44.7, 69.0, and 75.2% of patients in the placebo, taspoglutide 10-mg, and taspoglutide 20-mg groups, respectively. Serious AEs were reported in 10 patients (). Hypersensitivity reactions were reported in two patients receiving taspoglutide 10 mg (one moderate rash on left forearm, which occurred shortly after the first injection of trial medication, and one moderate systemic urticaria, which occurred on study day 163 after the last injection) and in two patients receiving taspoglutide 20 mg (one case of face redness moderate in intensity that started on study day 29 immediately after the patient had received the fifth dose of taspoglutide and one severe edema of the larynx and tongue that occurred shortly after the first dose of taspoglutide 10 mg and resolved 1 h after prednisone administered). No deaths occurred and no cases of pancreatitis were reported.
Gastrointestinal complaints were the most frequently reported AEs (). Injection site reactions occurred at a higher frequency in patients receiving taspoglutide than placebo. No cases of severe hypoglycemia were reported.
Withdrawal from treatment as a result of AEs occurred in 3.3, 11.2, and 13.2% of the placebo, taspoglutide 10-mg, and taspoglutide 20-mg groups, respectively ().