Takeda's investigational DPP-4 inhibitor demonstrated efficacy

June 25, 2007

Chicago, IL, June 23, 2007 -- Alogliptin, a highly selective dipeptidyl peptidase-IV (DPP-4) inhibitor under investigation for the treatment of type 2 diabetes, demonstrated efficacy in reducing glucose levels throughout the day, in an early phase clinical study. Safety results for this multi-dose study showed that alogliptin was well tolerated in patients with type 2 diabetes, with an incidence of hypoglycemia similar to placebo. No serious adverse event was reported, and no dose-limiting toxicity was observed over the entire dose range of 25 to 400 mg. The data were announced during a poster presentation at the 67th Scientific Sessions of the American Diabetes Association (ADA) meeting in Chicago. "These are encouraging early results for alogliptin as a potential new type 2 diabetes treatment to help manage glucose levels throughout the day,¡± said Qais A. Mekki, MD, PhD, vice president, Clinical Science at Takeda Global Research & Development, Inc.

"Alogliptin is a reflection of Takeda¡¯s commitment to finding innovative options to help patients manage their type 2 diabetes.¡±

Alogliptin Study Design

This was a randomized, double-blind, placebo-controlled, parallel-group, multi-dose study conducted in multiple centers. Subjects were patients with type 2 diabetes who were either newly diagnosed or treated with diet and exercise alone for the previous three months and were between the ages of 18 and 75 years.

The objectives of the study were to assess the uptake, utilization and metabolism, as well as the tolerability, of alogliptin after multiple-dose administration to patients with type 2 diabetes. The primary efficacy endpoint was change in mean 4-hour postprandial plasma glucose levels from Baseline (Day -1) to Day 14. Secondary efficacy endpoints included change in mean 4-hour postprandial insulin levels; fasting plasma levels of C-peptide, fructosamine, and glycosylated hemoglobin (A1C); and incidence of hyperglycemia (blood glucose = 200 mg/dL).

Fifty-five patients were assigned to receive alogliptin 25 (n=15), 100 (n=14), or 400 mg (n=15), or placebo (n=11) once daily for 14 days. Patients received three standardized meals a day and a snack after dosing on Days -1 (Baseline), 1 and 14. Blood and urine samples were collected through 24 hours after Day 1 and through 48 hours after Day 14.

Alogliptin Study Results

On Day 14, statistically significant decreases from Baseline in mean 4-hour plasma glucose levels were observed for 25, 100, and 400 mg doses, after each of three meals. These reductions were compared to those achieved by placebo: Alogliptin demonstrated rapid and sustained inhibition of plasma DPP-4 activity, across all doses: Secondary endpoint results showed that mean fasting fructosamine levels were significantly decreased from Baseline to Day 15 for the alogliptin 100 and 400 mg groups, compared to placebo, suggesting greater glucose control. There were no statistically significant differences in mean 4-hour postprandial insulin concentrations, hyperglycemia, or mean C-peptide concentrations in the alogliptin or placebo groups.

Alogliptin was well tolerated at all doses, with no patient discontinuation due to adverse events (AEs), and no serious AEs identified among patients through the duration of the study. In addition, there was a low incidence of hypoglycemia similar to placebo.
About Alogliptin

Alogliptin, initially referred to as SYR-322, is a highly selective and potent DPP-4 inhibitor and is under investigation for the treatment of type 2 diabetes. Alogliptin was designed by Takeda to selectively inhibit DPP-4 and not other closely related proteins that are associated with other biologic activity. In in vitro studies, alogliptin has been shown to be 10,000-fold more selective for DPP-4 over other closely related proteins.

DPP-4 inhibitors are a new class of oral agents for the treatment of type 2 diabetes that block the degradation of GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide), known as incretins, which are normally released in the digestive tract in response to food, and mediate glucose-dependent insulin secretion. GLP-1 also suppresses pancreatic glucagon secretion and subsequent liver glucose production, slows gastric motility and elicits satiety, a feeling of fullness. In type 2 diabetes, GLP-1 levels are decreased and the insulinotropic response to GIP is reduced, contributing to high blood sugar. DPP-4 inhibitors have displayed a weight-neutral profile along with a risk of low blood sugar similar to placebo due to their glucose-dependent mechanism of action.

Discovered by Takeda San Diego, Inc., alogliptin is being developed by Takeda Global Research & Development and is currently in Phase 3 clinical studies.

Takeda Global Research & Development Center, Inc.

Based in Deerfield, Ill., and London, U.K., Takeda Global Research & Development Center, Inc. is a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, the largest pharmaceutical company in Japan. Takeda Global Research & Development was established in 2004 and is responsible for Takeda¡¯s clinical research and development in the U.S. and Europe, supporting clinical and product development activity for Takeda commercial organizations in the U.S. ¨C Takeda Pharmaceuticals North America, Inc. - and in Europe: six sales and marketing companies, respectively. With a robust pipeline of compounds in development for diabetes, cardiovascular disease and other conditions, Takeda rapidly brings innovative products to market to improve patient health and enhance the practice of medicine. To learn more about the company, visit www.tgrd.com.

Takeda Pharmaceuticals North America

Related Diabetes Articles from Brightsurf:

New diabetes medication reduced heart event risk in those with diabetes and kidney disease
Sotagliflozin - a type of medication known as an SGLT2 inhibitor primarily prescribed for Type 2 diabetes - reduces the risk of adverse cardiovascular events for patients with diabetes and kidney disease.

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.

Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.

Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).

Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.

Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).

Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.

People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.

Read More: Diabetes News and Diabetes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.