Treatment with the human once-weekly glucagon-like peptide-1 analog taspoglutide in combination with metformin improves glycemic control and lowers body weight in patients with type 2 diabetes inadequately controlled with metformin alone: a double-blind placebo-controlled study.
OBJECTIVE
To evaluate the efficacy and safety of taspoglutide (R1583/BIM51077), a human once-weekly glucagon-like peptide-1 analog, in patients with type 2 diabetes inadequately controlled with metformin.


METHODS
Type 2 diabetic (n = 306) patients who failed to obtain glycemic control (A1C 7-9.5%) despite 1,500 mg metformin daily were randomly assigned to 8 weeks of double-blind subcutaneous treatment with placebo or taspoglutide, either 5, 10, or 20 mg once weekly or 10 or 20 mg once every 2 weeks, and followed for 4 additional weeks. All patients received their previously established dose of metformin throughout the study. Glycemic control was assessed by change in A1C (percent) from baseline.


RESULTS
Significantly greater (P < 0.0001) reductions in A1C from a mean +/- SD baseline of 7.9 +/- 0.7% were observed in all taspoglutide groups compared with placebo after 8 weeks of treatment: -1.0 +/- 0.1% (5 mg once weekly), -1.2 +/- 0.1% (10 mg once weekly), -1.2 +/- 0.1% (20 mg once weekly), -0.9 +/- 0.1% (10 mg Q2W), and -1.0 +/- 0.1% (20 mg Q2W) vs. -0.2 +/- 0.1% with placebo. After 8 weeks, body weight loss was significantly greater in the 10 mg (-2.1 +/- 0.3 kg, P = 0.0035 vs. placebo) and 20 mg (-2.8 +/- 0.3 kg, P < 0.0001) once-weekly groups and the 20 mg once every 2 weeks (-1.9 +/- 0.3 kg, P = 0.0083) group than with placebo (-0.8 +/- 0.3 kg). The most common adverse event was dose-dependent, transient, mild-to-moderate nausea; the incidence of hypoglycemia was very low.


CONCLUSIONS
Taspoglutide used in combination with metformin significantly improves fasting and postprandial glucose control and induces weight loss, with a favorable tolerability profile.
Nauck
Michael A
MA
Diabeteszentrum, Bad Lauterberg im Harz, Germany.
Ratner
Robert E
RE
Kapitza
Christoph
C
Berria
Rachele
R
Boldrin
Mark
M
Balena
Raffaella
R
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D017698:Postmenopause; D012449:Safety; D013245:Sterilization, Reproductive
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D008687:Metformin; D010455:Peptides; C541736:taspoglutide