# Carbazoles: Role and Functions in Fighting Diabetes
## 1 Introduction
\begin{table}
\begin{tabular}{l l l} \hline \hline
**DRUG CLASS** & **MECHANISM OF ACTION** & \multicolumn{2}{c}{**MORE COMMON SIDE EFFECTS**} \\  & & **AND DISADVANTAGES** \\ \hline  & & Gastrointestinal side effects (diarrhea, \\  & & abdominal cramping); \\
**BIGUANIDES:** & AMP-Kinase activation; & Lactic acidosis risk; \\
**Metformin** & Decrease in hepatic glucose production. & Vit B12 deficiency; \\  & & Hypoxia; \\  & & Dehydration. \\ \hline
**SULPHONYLUREAS:** & & \\
**Glibenclamide** & Closure of KATP channels on \(\beta\) cell & \\
**Glicclazide** & plasma membranes; & Hypoglycemia; \\
**Glipizide** & Increase in insulin secretion. & Weight gain. \\
**Glimpeniride** & & \\ \hline
**GLINIDES (MEGLITINIDES):** & Closure of KATP channels on \(\beta\) cell & \\
**Repaglinide** & plasma membranes; & Hypoglycemia; \\
**Nateglinide** & Increase in insulin secretion. & Weight gain. \\ \hline
**\(\alpha\)-GLUCOSIDASE INHIBITORS:** & Inhibition of intestinal & \\
**Acarbose** & \(\alpha\)-glucosidase; & Generally modest HbA1c efficacy; \\
**Miglitol** & Intestinal carbohydrate digestion and & Gastrointestinal side effects (flatulence, \\  & absorption reduction. & diarrhea). \\ \hline
**THIAZOLIDINEDIONES (TZDs):** & Nuclear & Weight gain; \\
**Piogltazone** & transcription factor PPAR-\(\gamma\) activation; & Edema; \\
**Rosigltazone** & Increase in insulin sensitivity. & Heart failure; \\
**Lobeglitazone** & & Bone fractures. \\ \hline
**DPPA INHIBITORS (GLIPTINS):** & DPP-4 inhibition; & \\
**Sitagliptin** & Increase in postprandial active incretin & \\
**Vildagliptin** & (GLP-1, GIP) concentrations; & Generally modest HbA1c efficacy; \\
**Saxagliptin** & Increase in glucose-dependent insulin & Uricaria; \\
**Alogliptin** & secretion; & Angioedema. \\
**Alogliptin** & Decrease in glucose-dependent glucagon & \\
**Linagliptin** & secretion. & \\ \hline
**GLP-1 AGONISTS:** & GLP-1 receptors activation; & \\
**Exenatide** & Increase in glucose-dependent insulin & \\
**Liragludite** & Decrease in glucose-dependent glucagon & Gastrointestinal side \\
**Lixsenatide** & secretion.; & effects (nausea/vomiting); \\
**Dulaglutide** & Slowing of gastric emptying; & C-cell hyperplasia. \\  & Satiety increase. & \\ \hline
**SGLT2 INHIBITORS:** & Block of sodium/glucose cotransporter 2 & Renal failure; \\
**Dapagliflozin** & (SGLT2) in renal tubules & Increased risk of genital and urinary trac \\
**Dapagliflozin** & Reduction of glucose reabsorption in the & fungal infection; \\
**Empagliflozin** & kidney; & Increased risk of euglycemic diabetic \\
**Canagliflozin** & Decrease in serum blood glucose level. & ketoacidosis. \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Classes of antidiabetic medications. Metformin, one of the most commonly used oral hypoglycemic drugs, acts, for example, by increasing the utilization of glucose in peripheral tissues and by decreasing hepatic glucose production. Sulfonylureas, on the other hand, are able to modulate blood glucose levels by stimulating insulin secretion from pancreatic beta cells. Thiazoltionedes (TZDs) binds the peroxisome proliferator-activated receptor (PPAR) gamma, a transcription factor that regulates the expression of specific genes, and improves the sensitivity of fatty tissue, skeletal muscles and liver to insulin. More recently, new classes of drugs able to control hyperglycemia have been introduced. Among these, incretins, DPP-4 resistant GLP-1 analogs, and DPP-4 inhibitors play an important role; they are able to promote an increase in endogenous GLP-1 levels and stimulate pancreatic cells to release insulin. SGLT2 inhibitors increase glucose excretion in the urine by preventing glucose reabsorption in the renal tubules. Despite the therapeutic goals achieved by this diverse range of diabetes drugs, their clinical use is associated with undesirable side effects (summarized in Table 1), including dangerous hypoglycemic episodes [11].