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

In September 2010, Roche announced cessation of dosing in the Taspoglutide clinical trial program pending further analysis of the safety and immunogneicity of Taspoglutide.