Pirogliride is the antidiabetic agent. It has been found to produce a hypoglycemic effect in nondiabetic rats, dogs, mice, and monkeys. To being three to four times more potent than tolbutamide, pirogliride also differs from the sulfonylureas in lowering blood glucose concentrations of streptozotocin-diabetic rats and db/db mice, and, moreover, oral administration to normal fasted dogs did not produce the characteristic rise in insulin concentrations observed with tolbutamide. Pirogliride potentiates glucose-induced insulin secretion from isolated islets. This effect is accompanied by a facilitated glucose metabolism. Pirogliride partially prevents the known inhibitory effects of mannoheptulose on glucose-induced secretion and utilization. Pirogliride was found to produce a concentration-dependent inhibition of gluconeogenesis in rat kidney cortex slices. hepatocytes and perfused liver. Pirogliride was metabolized in man to a small extent by oxidation of the 4-position of the phenyl ring.

Trapencaine (pentacaine) is a local anesthetic, used as an antiulcerogenic agent. A proportional involvement of local and systemic effects of pentacaine was found in phenylbutazone-induced and cold-resistant stress-induced lesions, whereas in ethanol-induced lesions oral administration was the only effective way. On the other hand, duodenal lesions and gastric acid secretion were substantially affected by parenteral administration. Pentacaine prevented the depletion of mucus after stress in rats. Intraduodenal administration of pentacaine significantly suppressed both the basal and stimulated gastric secretion.

Imeglimin is the first in class tetrahydrotriazine‐containing oral glucose-lowering agent that has been studied in clinical trials as a possible monotherapy or add-on therapy to lower fasting plasma glucose. It is being developed as an alternative and a complement to drugs that act on insulin‐resistant organs or drugs acting on insulin secretion and β‐cell protection. When investigated in preclinical studies, Imeglimin showed that it can target insulin‐resistant organs by decreasing excessive hepatic glucose production and increasing muscle glucose uptake. It also showed a potential to restore appropriate glucose‐stimulated insulin secretion and protect β‐cells from cell death under high glucose conditions. Imeglimin acts on the liver, muscle, and the pancreas (6), three key organs involved in the pathophysiology of type 2 diabetes through suspected mechanisms targeting the mitochondria and reduced oxidative stress. Imeglimin decreases hepatic glucose production and increases muscle glucose uptake. Recently, Imeglimin demonstrated increased insulin secretion in response to glucose in diabetic patients during a hyperglycemic clamp study. In clinical trials, Imeglimin treatment for 7 days raised the insulin secretory response to glucose, improved β-cell glucose sensitivity and tended to decrease hepatic insulin extraction. Imeglimin did not affect glucagon secretion.

Johnson and Johnson was developing usistapide, a microsomal triglyceride transfer protein (MTTP) inhibitor, for the treatment of obesity and type 2 diabetes. Usistapide, also known as JNJ-16269110 and R256918, has been used in trials studying the treatment of obesity, overweight, metabolic diseases, nutrition disorders, and nutritional and metabolic diseases. Usistapide was removed from the company pipeline and appears to have been discontinued.

Sipoglitazar (TAK 654) was a novel, azolealkanoic acid derivative that possesses selective activity for the peroxisome proliferator-activated receptors (PPAR) PPARγ, PPARα, and PPARδ. Sipoglitazar was developed to improve peripheral insulin sensitivity, normalize circulating lipid profiles, and reduce body weight in patients with metabolic syndrome and type 2 diabetes mellitus (T2DM). Sipoglitazar was being developed by Takeda for the treatment of diabetes mellitus, however in September 2006, development was discontinued.

Ufiprazole (Omeprazole sulfide) is a metabolite of Omeprazole, which is a proton pump inhibitor. Omeprazole sulfide has been shown to be a direct-acting inhibitor of CYP2C19 in pooled human liver microsomes. Ufiprazole is also a weak BRS-3 agonist.

Lorglumide (CR1409) is the first nonpeptidic, selective and potent inhibitor of the cholecystokinin-A and cholecystokinin-B receptors. Lorglumide prevented dose-dependently the emptying of the gallbladder in both experimental models; proglumide exhibited a comparable activity at much higher doses. Lorglumide was associated with significantly inhibited cell growth of human pancreatic cancer cell line Mia PaCa-2 in vitro. Lorglumide also induced G0/G1 cell cycle arrest and apoptosis. The change of invasion ability appeared to be mediated by MMP-2 expression, which was upregulated by CCK-8S and downregulated by lorglumide. Lorglumide had been in preclinical phase for the treatment of biliary dyskinesia, pancreatitis and cancer. However, this development was discontinued.

Nufenoxole is an orally active antidiarrhoeal agent which binds to opioid receptors in the brain and myenteric plexus of the intestine. Nufenoxole is well absorbed in rat, monkey and human after oral administration. Systemic availability of nufenoxole was 85% in monkey and 102% in man. The elimination rate was much faster in rat (t1/2 of 1.8 h) and monkey (t1/2 of 4.9 h) compared with human (t1/2 of 35.8 h). Nufenoxole possesses potent antisecretory properties, which are mediated via opioid receptors and may contribute to its antidiarrhoeal action in man.

Tazasubrate was developed as a lipid-lowering agent. Tazasubrate was found to be a reliable and highly effective hypocholesterolemic agent. However, information about the current use of this compound is not available.