A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Dose-Response, Multicentre, Multinational Study Evaluating the Efficacy and Safety of AVE2268 Administered Either Twice Daily (Breakfast and Lunch) at a Dose of 300, 600 and 1200 mg or Once Daily (Breakfast) at a Dose of 1200 mg, in Patients With Type 2 Diabetes Treated With Metformin and Not Adequately Controlled

Dose-ranging study of AVE2268 in the management of patients with type 2 diabetes mellitus also receiving metformin.
Its main objectives will be to assess the effects of several doses of AVE2268 on Mean Plasma Glucose. Its secondary objectives will be to assess the effects of AVE2268 on plasma glucose (fasting and post-prandial), and also the safety and tolerability of AVE2268.

Start Date01 Jul 2006

Sponsor / Collaborator

Sanofi

100 Clinical Results associated with Atigliflozin

100 Translational Medicine associated with Atigliflozin

100 Patents (Medical) associated with Atigliflozin

Literatures (Medical) associated with Atigliflozin

01 Feb 2021·Journal of Labelled Compounds and Radiopharmaceuticals

The magic of small structure differences in a sodium‐glucose cotransporter drug discovery project—¹⁴C‐labelled drug candidates in a key‐differentiating study

Article

Author: Schudok, Manfred ; Glombik, Heiner ; Derdau, Volker

We describe the dramatic differences in the synthesis and physiological and pharmacokinetical profiling of two sodium‐glucose cotransporter (SGLT) drug candidates AVE2268 and AVE8887 with very similar chemical structures. It is a classic example of how a radioactive study was able to spare resources in preclinical development prior to entering a costly clinical program. It also demonstrated that radioactive compounds can be used to study differences between two very similar compounds in vivo.

01 Jan 2015·DiabetesQ1 · MEDICINE

Metformin Supports the Antidiabetic Effect of a Sodium Glucose Cotransporter 2 Inhibitor by Suppressing Endogenous Glucose Production in Diabetic Mice

Q1 · MEDICINE

Article

Author: Wurst, Wolfgang ; Beckers, Johannes ; Suhre, Karsten ; Wolf, Eckhard ; Scheerer, Markus ; Wu, Moya ; Rathkolb, Birgit ; Hrabé de Angelis, Martin ; Seelig, Anett ; Schultheiss, Jürgen ; Huypens, Peter ; Neschen, Susanne

Combined use of metformin and a sodium glucose cotransporter 2 inhibitor (SGLT2I) is a promising treatment strategy for type 2 diabetes. The mechanism by which combination treatment provides better glycemic control than metformin or SGLT2I monotherapy remains elusive. Therefore, we investigated the physiological mechanism by which both compounds lower blood glucose concentrations in diabetic mice. We compared the potential of metformin and the SGLT2I AVE2268 alone or in combination to mitigate hyperglycemia and modulate glucose fluxes in db/db and diabetic Tallyho/JngJ mice. SGLT2I treatment alone elicited a rapid decline in circulating blood glucose levels, which appeared to induce endogenous glucose production. Supplementation of metformin dampened this counterresponse, and therefore, combination therapy more efficiently maintained glycemic control. Finally, combination treatment blunted postprandial glucose excursions and improved HbA1c levels within 2 weeks. We conclude that coapplication of metformin enhances the glucose-lowering actions of SGLT2I by restraining endogenous glucose production, which may provide long-term improvement of glycemic control in type 2 diabetic patients.

01 Apr 2013·Diabetes, Obesity and MetabolismQ2 · MEDICINE

Energy loss via urine and faeces – a combustive analysis in diabetic rats and the impact of antidiabetic treatment on body weight

Q2 · MEDICINE

Article

Author: Glombik, H. ; Wille, A. ; Werner, U. ; Wandschneider, J. ; Herling, A. W. ; Elvert, R.

AimsIntensive glycaemic control in type 2 diabetes achieved by insulin is generally accompanied by body weight gain. This study was performed to emphasize the meaning of caloric analysis of urine and faeces for energy balance.MethodsWe measured energetic loss via urine and faeces during antihyperglycaemic treatment in male obese Zucker diabetic fatty (ZDF) rats. Rats were treated for 10 days with the sodium–glucose‐linked transporter‐2 (SGLT2) inhibitor AVE2268, with insulin glargine, with the GLP‐1 receptor agonist lixisenatide and with the combination of insulin glargine and lixisenatide. Each study was accompanied by one lean (Fa/?) and one obese (fa/fa) untreated non‐diabetic and diabetic control group, respectively. Blood glucose, body weight alterations and food assimilation efficiency were monitored.ResultsIn control ZDF rats, more than 12 g/day of pure glucose was urinarily excreted. In total, the energetic loss via urine exceeded 30% from total energy uptake. Insulin glargine treatment decreased urinary energetic loss, leading to a body weight gain of approximately 3 g/day. An almost body weight‐neutral antihyperglycaemic treatment could be achieved with AVE2268 and lixisenatide. While lixisenatide reduced body weight gain via reduction of energy uptake, the SGLT2 inhibitor even increased urinary glucose and thus energy excretion. Combining insulin glargine with lixisenatide attenuated the anabolic effect of insulin resulting in weight neutrality.ConclusionsOur data clearly show renal contribution to the body's energy control by urinary glucose excretion (UGE) during antidiabetic treatment. The undesired retained energy could be reduced via additional UGE or via simultaneous reduction of energy uptake and/or energy retention.

100 Deals associated with Atigliflozin

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Phase 2	AR	Sanofi	01 Jul 2006
Diabetes Mellitus, Type 2	Phase 2	FR	Sanofi	01 Jul 2006
Diabetes Mellitus, Type 2	Phase 2	ZA	Sanofi	01 Jul 2006
Diabetes Mellitus, Type 2	Phase 2	IT	Sanofi	01 Jul 2006
Diabetes Mellitus, Type 2	Phase 2	BE	Sanofi	01 Jul 2006
Diabetes Mellitus, Type 2	Phase 2	DK	Sanofi	01 Jul 2006
Diabetes Mellitus, Type 2	Phase 2	CL	Sanofi	01 Jul 2006
Diabetes Mellitus, Type 2	Phase 2	AU	Sanofi	01 Jul 2006
Diabetes Mellitus, Type 2	Discovery	PL	Sanofi	01 Jul 2006
Diabetes Mellitus, Type 2	Discovery	DE	Sanofi	01 Jul 2006

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