Type 2 Diabetes Mellitus: A Review of Multi-Target Drugs

Abstract

Diabetes Mellitus (DM) is a multi-factorial chronic health condition that affects a large part of population and according to the World Health Organization (WHO) the number of adults living with diabetes is expected to increase. Since type 2 diabetes mellitus (T2DM) is suffered by the majority of diabetic patients (around 90–95%) and often the mono-target therapy fails in managing blood glucose levels and the other comorbidities, this review focuses on the potential drugs acting on multi-targets involved in the treatment of this type of diabetes. In particular, the review considers the main systems directly involved in T2DM or involved in diabetes comorbidities. Agonists acting on incretin, glucagon systems, as well as on peroxisome proliferation activated receptors are considered. Inhibitors which target either aldose reductase and tyrosine phosphatase 1B or sodium glucose transporters 1 and 2 are taken into account. Moreover, with a view at the multi-target approaches for T2DM some phytocomplexes are also discussed.

Dual-Target Compounds against Type 2 Diabetes Mellitus: Proof of Concept for Sodium Dependent Glucose Transporter (SGLT) and Glycogen Phosphorylase (GP) Inhibitors

“…In this respect, the fields of cancer [ 8 ] and neurodegeneration [ 9 ] have been surveyed. In the context of T2DM, the development of such multi-target drugs has recently been reviewed [ 10 , 11 , 12 ] to highlight agonists acting on incretin, glucagon systems, and peroxisome proliferation activated receptors, just to mention a few. Another interesting example is the dual inhibition of aldose reductase (AR, IC 50 0.056 μM) and protein tyrosine phosphatase 1B (PTP1B, IC 50 32.5 μM) by a (5-arylidene-4-oxo-2-thioxothiazolidin-3-yl)acetic acid derivative with the potential to treat T2DM [ 13 ].…”

Identification and Comparison of Peptides from Chickpea Protein Hydrolysates Using Either Bromelain or Gastrointestinal Enzymes and Their Relationship with Markers of Type 2 Diabetes and Bitterness

“…Since there is a complex system in the control of glucose levels and insulin production in the body, there are multiple targets for foods and drugs to treat T2DM. Targets that have been explored in the past include dipeptidyl peptidase-IV (DPP-IV), α-amylase and α-glucosidase inhibitors [ 9 , 10 , 11 ]. The enzymes α-amylase and α-glucosidase participate in the digestion of starch from food; therefore, the inhibition of these markers decreases the glucose available for intestinal absorption and metabolism.…”

Incretin Hormones in Obesity and Related Cardiometabolic Disorders: The Clinical Perspective

“…This is due to the fact that the pancreas is no longer responsive to GIP; however, it does remain sensitive to GLP-1 [ 12 ]. Thus, incretin-based glucose-lowering medications, in particular GLP-1 receptor agonists (GLP-1RAs), have proven to be effective and are currently used in T2DM treatment [ 13 , 14 , 15 , 16 , 17 , 18 ]. A similar observation of decreased incretin effect was made in obese individuals with normal glucose tolerance.…”