Type 2 Diabetes Mellitus (T2DM) and Alzheimer's disease (AD) are the two 
disorders which are known to share pertinent pathological and therapeutic links. 
Sodium glucose co-transporter-2 (SGLT2) and Acetylcholinesterase (AChE) are 
established inhibition targets for T2DM and AD treatments, respectively. Reports 
suggest that anti-diabetic drugs could be used for AD treatment also. The 
present study used molecular docking by Autodock4.2 using our 
"Click-By-Click"-protocol, Ligplot1.4.3 and "change in accessible surface area 
(ΔASA)-calculations" to investigate the binding of two investigational 
anti-diabetic drugs, Ertugliflozin and Sotagliflozin to an established target 
(SGLT2) and a research target (human brain AChE). Sotagliflozin appeared more 
promising for SGLT2 as well as AChE-inhibition with reference to ΔG and Ki 
values in comparison to Ertugliflozin. The ΔG and Ki values for 
"Sotagliflozin:AChE-binding" were -7.16 kcal/mol and 5.6 μM, respectively while 
the same were found to be -8.47 kcal/mol and 0.62 μM, respectively for its 
interaction with SGLT2. Furthermore, "Sotagliflozin:SGLT2-interaction" was 
subjected to (un)binding simulation analyses by "Molecular-Motion-Algorithms." 
This information is significant as the exact binding mode, interacting amino 
acid residues and simulation results for the said interaction have not been 
described yet. Also no X-ray crystal is available for the same. Finally, the 
results described herein indicate that Sotagliflozin could have an edge over 
Ertugliflozin for treatment of Type 2 diabetes. Future design of drugs based on 
Sotagliflozin scaffolds for treatment of Type 2 and/or Type 3 diabetes are 
highly recommended. As these drugs are still in late phases of clinical trials, 
the results described herein appear timely. J. Cell. Biochem. 118: 3855-3865, 
2017. © 2017 Wiley Periodicals, Inc.