Taspoglutide is a human GLP-1 analoge with 2 alpha-aminoisobutyric acid substitutions replacing Ala(8) and Gly(35) of hGLP-1(7-36)NH2. Taspoglutide binds to and activates the GLP-1 receptor in a GLP-1-receptor-dependent manner in vitro and in vivo, and exhibits resistance to DPP-4 inhibition. Taspoglutide, an analog of human glucagon-like Peptide-1 with enhanced stability and in vivo potency Endocrinology. 2010 Jun;151(6):2474-82.
The pharmacokinetics of taspoglutide have been studied in human subjects with type 2 diabetes following single dose administration of 1, 8 or 30 mg. Taspoglutide plasma levels peaked within 24 h and were sustained for at least 14 days, consistent with the proposed once weekly dosing profile for this agent Pharmacokinetic and pharmacodynamic properties of taspoglutide, a once-weekly, human GLP-1 analogue, after single-dose administration in patients with Type 2 diabetes. Diabet Med. 2009 Nov;26(11):1156-64.
An eight week study examined Taspoglutide efficacy in combination with metformin in subjects with type 2 diabetes. Taspoglutide dosing was studied at either 5, 10, or 20 mg once weekly or 10 or 20 mg once every 2 weeks for 8 weeks of active treatment, then an additional 4 weeks of follow-up. Taspoglutide therapy significantly reduced A1c, body weight, and both fasting and postprandial glucose, with nausea reported as the predominant AE. See 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 Diabetes Care. 2009 Jul;32(7):1237-43.
A second Phase 2 study examined a range of Taspoglutide doses, from 20-40 mg once weekly, in subjects with type 2 diabetes. GI complaints were the most commonly reported Adverse Events and the proportion of subjects achieving HbA(1c) < 7.0% after 8 weeks of treatment was 72, 53 and 70% in the 20/20-, 20/30- and 20/40-mg arms Safety and tolerability of high doses of taspoglutide, a once-weekly human GLP-1 analogue, in diabetic patients treated with metformin: a randomized double-blind placebo-controlled study Diabet Med. 2010 May;27(5):556-62.
The Phase 3 program for Taspoglutide has been designated The T-emerge Phase III clinical trial programme. This is designed as a series of multicentre, multi-country, randomized, controlled (active or placebo), double-blind and open studies. Over 6,000 patients will be enrolled in the eight studies that comprise the T-emerge programme. Studies include two parallel taspoglutide arms including 10 mg once weekly and 10 mg once weekly titrated up to 20 mg once weekly after 4 weeks. Four of the eight studies have active comparators, including exenatide, sitagliptin, insulin glargine and pioglitazone.
T-emerge 1: Double-blind, randomized, placebo-controlled study versus placebo in 373 treatment-naïve type 2 diabetes patients (taspoglutide at doses of 10 and 20 mg, and placebo).
T- emerge 2: Open-label core study versus exenatide, involving 1189 patients, equally randomized into three active arms (taspoglutide at doses of 10 and 20 mg, and exenatide 10-?g).
T-emerge 3: A study of once weekly taspoglutide versus placebo, as add-on to metformin and pioglitazone
T-emerge 4: Head-to-head comparison study versus sitagliptin (Januvia®) as add-on to metformin involving 636 patients who have failed to reach their treatment targets with metformin (taspoglutide at doses of 10 and 20 mg, sitaglipton, and placebo).
T-emerge 5: Head-to-head comparison study of taspoglutide versus insulin glargine (Lantus®) as add-on to metformin in patients failing on metformin and sulfonylurea with 1,049 patients equally randomized into three arms (taspoglutide at doses of 10 mg and 20 mg, and insulin glargine once daily).
T-emerge 6: Head to head vs. pioglitazone in subjects receiving a background therapy of SU with or without metformin
T-emerge 7: Combination therapy study of taspoglutide as add-on to metformin in patients with high BMI involving 305 patients equally randomized into two arms (taspoglutide at a dose of 20 mg, and placebo).
T-emerge 8 CVS study to generate enough CV endpoints to meet FDA guidance
On June 18 2010, Roche announced in a Press Release that less than 1% of patients receiving Taspoglutide in Phase 3 clinical trials developed symptoms consistent with allergic reactions, including GI upset and skin irritation. Results from several of the T-emerge studies were presented at the 2010 ADA Meeting in Orlando