In two recent trials, the investigational drug GFT505 improved lipid and glucose disorders in abdominally obese patients with combined dyslipidemias or prediabetes.…
Lead author Dr. Bertrand Cariou from Nantes University Hospital, Nantes, France stated that, “I think this new compound will be a valuable target to prevent cardiovascular risk in this specific population by improving lipid profile, potentially decreasing insulin resistance and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.
GFT505 stimulates both the alpha and delta peroxisome proliferator-activated receptors (PPARs). The researchers contend that, GFT505 will be more efficient than fibrates in this setting, due to its specific PPAR delta activity. Fibrates are PPAR-alpha agonists.
Both studies were randomized phase IIa trials. One involved 94 patients with combined dyslipidemia who took GFT505 or placebo for 28 days (study 1, S1). The other included 47 patients with prediabetes who took one or the other for 35 days (study 2, S2).
Compared to placebo, GFT505 reduced fasting plasma triglyceride levels by 16.7% in S1 and by 24.8% in S2, increased HDL cholesterol by 7.8% in S1 and by 9.3% in S2, and decreased total cholesterol by 8.7% in S2 only. All lipid values returned to baseline two weeks after treatment ended.
Prediabetic patients in S2 assigned to GFT505 had small but significant reductions in fasting plasma glucose and fructosamine, plus significant decreases in fasting insulinemia and improved insulin sensitivity.
GFT505 also reduced gamma glutamyl transferase, alanine aminotransferase, alkaline phosphatase, haptoglobin, and fibrinogen levels, whereas levels of aspartate aminotransferase and C-reactive protein did not change significantly.
GFT505 was well tolerated, with no serious adverse effects and no treatment-related discontinuation.
Dr. Cariou said, “In the light of the results of this pilot study, I hope that the readers will be convinced by the potential of dual PPAR alpha/delta agonists, and that this new class will add a benefit in term of cardiovascular prevention when compared to pure PPAR alpha agonists (i.e., fibrates).”
He said three phase III studies are planned: one in drug-naive type 2 diabetics; one in patients with abdominal obesity and insulin resistance; and one in patients with NASH.
Last month positive results of GFT505 were reported in a 12-week trial in diabetics. The company said in a statement that compared to baseline levels, HbA1c fell by 0.4% (p=0.01), 2 hour glycemia upon oral glucose tolerance testing (OGTT) fell by 38 mg/dL (p<0.001), and the area under the curve for glycemia upon OGTT fell by 39 mg/dL (p<0.001) -- whereas none of these parameters was altered in the placebo group. There was also a trend toward a reduction in fasting glycemia with GFT505. Treatment also lowered patients' triglycerides and non-HDL cholesterol, increased their HDL cholesterol, and improved markers of hepatic dysfunction.
Diabetes Care August, 2011