Imeglimin is the first clinical candidate in a new chemical class of oral agents called the glimins by the World Health Organization. Imeglimin acts on the three key organs which play an important role in the current anti-diabetic treatment paradigm: the liver, muscles, and the pancreas.1 In several studies conducted to date, imeglimin has demonstrated potential glucose-lowering effects through increased insulin secretion in response to glucose2, increased insulin sensitivity3, and suppression of gluconeogenesis.4 Imeglimin’s mechanism of action also has the potential to prevent diastolic dysfunction5, 6, 7 and to provide protective effects on beta cell survival and function.8
A total of 18 phase 1 and phase 2 clinical trials have been conducted studying imeglimin with over 1,200 patients with T2D in the U.S., Europe, and Japan, which have met their primary and secondary endpoints, including a statistically significant decrease of HbA1c and fasting plasma glucose versus placebo with a favorable side effect profile.9 Metavant plans to initiate differentiation studies to confirm imeglimin’s therapeutic potential in underserved patient populations with unfulfilled medical needs, such as those with chronic kidney disease, in 2018.
RVT-1502 (formerly LGD-6972) is a novel, orally-bioavailable, small molecule, glucagon receptor antagonist (GRA). Overproduction of glucose by the liver is an important cause of hyperglycemia (high glucose levels) in patients with diabetes and is due in part to inappropriately elevated levels of glucagon. GRAs may lower glucose levels by reducing the production of glucose by the liver.
RVT-1502 has been tested in multiple phase 1 and 2 studies, with pharmacokinetics supporting once-daily oral dosing. In those studies, statistically significant reductions in fasting plasma glucose, postprandial glucose, and HbA1c in patients with type 2 diabetes have been observed.10, 11
A phase 2 clinical study evaluating RVT-1502 as an adjunct to diet and exercise in patients with type 2 diabetes showed statistically significant improvement in hemoglobin A1c (HbA1c) (p < 0.001) after 12 weeks of treatment at all doses tested compared to placebo.12 In the study, RVT-1502 was observed to be well-tolerated by study subjects. Metavant intends to commence proof-of-concept studies for RVT-1502 in type 1 diabetes in 2018.