A Phase III DPP-4 Inhibitor for Type 2 Diabetes
GLP-1 and GIP are incretins that regulate blood glucose levels by increasing insulin release and decreasing glucagon secretion. Dipeptidyl peptidase 4 (DPP-4) is an enzyme that degrades GLP-1 and GIP. The inhibition of DPP-4 preserves the functions of GLP-1 and GIP to control the blood glucose level.
Retagliptin is a clinical-stage DPP-4 inhibitor to address type 2 diabetes. In completed phase II trials, retagliptin monotherapy or in combination with metformin significantly decreased the HbA1c level in type 2 diabetic patients.
Two phase III trials for retagliptin monotherapy aCnd in combination with metformin, respectively, are ongoing in China.
A Phase III SGLT2 Inhibitor for Type 2 Diabetes
Sodium-glucose transport protein 2 (SGLT2) is the major co-transporter responsible for 90% of glucose reabsorption in the kidney. The inhibition of SGLT2 decreases blood glucose levels by reducing urine glucose reabsorption and increasing glucose excretion.
SHR3824 is a clinical-stage SGLT2 inhibitor to address type 2 diabetes. In completed phase II trials, SHR3824 monotherapy or in combination with metformin effectively decreased the HbA1c, FPG, 2h PPG, body weight, and blood pressure in type 2 diabetes patients.
Two phase III trials for SHR3824 monotherapy and in combination with metformin, respectively, are ongoing in China.
A Subcutaneous Injectable GLP-1 Receptor Agonist
Glucagon-like peptide-1 (GLP-1) is one of incretins that increases insulin secretion and inhibits glucagon release when glucose levels are elevated. GLP-1 is an important target for type 2 diabetes since it has the potential of decreasing plasma glucose levels with low risk of hypoglycemia.
SHR20004 is a clinical-stage subcutaneous injectable GLP-1 receptor agonist. Three phase I clinical trials for SHR20004 were completed in China, and one phase II trial is ongoing.
An Oral GLP-1 Receptor Agonist
Glucagon-like peptide-1 (GLP-1) is one of incretins that increases insulin secretion and inhibits glucagon release when glucose levels are elevated. GLP-1 is an important target for type 2 diabetes because it has the potential of decreasing plasma glucose levels with low risk of hypoglycemia.
SHR-2042 is a clinical-stage oral GLP-1 receptor agonist. One phase I clinical trial to evaluate the safety and tolerance of SHR-2042 was completed in the U.S.
A Clinical-Stage Long-Acting Basal Insulin
In patients with diabetes, the destruction or dysfunction of beta cells of pancreatic islets results in less secretion of insulin, and thus leads to high blood glucose levels. Administration of basal insulin helps diabetic patients to maintain a needed level of insulin and to keep their blood glucose in stable levels during period of fasting.
INS068 is a clinical stage long-acting basal insulin. A phase I clinical trial to treat diabetes is ongoing in the U.S.
A Novel ROMK Inhibitor
The renal outer medullary potassium channel (ROMK) plays a key role in renal salt and water retention, which is important for blood pressure regulation. ROMK inhibitors show diuretic/natriuretic efficacy to lower blood pressure and treat hypertension.
SHR0532 is a selective inhibitor of ROMK. SHR0532 is currently assessed in a phase I clinical trial for the treatment of hypertension in China.
A Novel Anti-PCSK9 Antibody
Proprotein convertase subtilin/kexin type 9 (PCSK9) binds to low-density lipoprotein receptors (LDLR), enhancing the lysosomal degradation of LDLR. The blockage of PCSK9 increases LDLR recycling; therefore, more LDLRs are presented on the cell membranes to uptake LDL into cells. As a result, PCSK9 blockage decreases blood LDL concentrations.
SHR-1209 is a PCSK9 inhibitor being developed for hypercholesterolemia. SHR-1209 is currently under phase I development in China.