This chapter firstly presents selected clinical studies to evaluate the current drugs
as well as emerging new drugs for type 2 diabetes mellitus (T2DM) and obesity, and
secondly presents future drug candidates under pharmacological research. The current
drugs are α-glucosidase inhibitors, glinide, sulfonylurea (SU), incretin-based therapies,
including dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1)
receptor agonist, thiazolidinediones (TZDs), biguanides, insulin, in particular, short acting
and long acting insulin analogs. Anti-obesity drugs available at present are intestinal lipase
inhibitor. Most of central regulators of appetite are not used mainly because of their
cardiovascular adverse events. Better glycemic control was compared among various drug
combinations; DPP-4 inhibitors vs. TZDs add-on to metformin, DPP-4 inhibitors vs.GLP-1
receptor agonist add-on to metformin or other oral hypoglycemic therapy (LEAD-6),
DPP-4 inhibitors vs. placebo with and without SU, short acting insulin analog vs. DPP-4
inhibitors add-on to metformin (EASIE study) or vs. placebo on GLP-1 receptor
agonist add-on to metformin and SU. Effects on morbidity and mortality have been
evaluated between intensive and conventional glycemic control. Intensive glycemic control
caused more frequent severe hypoglycemia and did not necessarily ameliorate prognosis
being much better as compared with conventional glycemic control. Effects were also
evaluated among the following drugs; DPP-4 inhibitors vs. SU, glinide (NAVIGATOR
study), basal supported oral therapy (BOT), basal plus or basal bolus (ORIGIN trial), and
insulin vs. other anti-hyperglycemic therapies. Emerging new drugs for T2DM and obesity
are salt glucose cotransporter 2 (SGLT2) inhibitors, glucokinase activators, and anti-obesity
drugs such as lorcaserin and phentermine-topiramate, both of which are central appetite
regulators with less adverse events. These are prospective drugs but still need investigations
to decide their clinical usefulness and safety. Pharmacological research for T2DM and
obesity are underway. Various new drugs such as the following may be promising; cyclindependent
kinase 5 inhibitor, leptin, adiponectin mimetics, SIRT1 activators, neuropeptide
Y2 receptor antagonist, 11-hydroxysteroid dehydrogenase type 1 inhibitor, interleukin-6,
betatrophin, chemerin, dilauroyl phosphatidylcholine, 1- deoxynojirimycin, fibroblast
growth factor(FGF)21, FGF1 and stearoyl-coenzyme A desaturase-1 inhibitors.
Keywords: Type 2 diabetes mellitus, obesity, drug, randomized control trial,
pharmacological research, metformin, incretin-based therapies, DPP-4 inhibitors,
GLP- 1 receptor agonist, insulin, glycemic control, morbidity, mortality
