The role of hormonal treatment in type 2 diabetes mellitus

Figures & data

Table 1 Classification of nonhormonal antihyperglycemic agents

Antidiabetic agents	Basic mechanism
Insulin sensitizers
Biguanides
Metformin	Activation of adenosine monophosphate kinase Inhibition of gluconeogenesis Increase insulin sensitivity Improve beta-cell function
Thiazolidinediones
Pioglitazone, rosiglitazone	Activation of PPAR-γ Increase glucose transporter expression (GLUT 1 and GLUT 4) Decrease gluconeogenesis Increase differentiation of preadipocytes into adipocytes
Insulin secretagogues
Sulfonylureas
Gliclazide, glimepiride, glipizide, glibenclamide (glyburide)	Stimulate insulin release from pancreatic beta cells by inhibiting potassium ATP channels
Non-sulfonylureas
Repaglinide, nateglinide
Alpha-glucosidase inhibitors
Acarbose	Inhibition of disaccharidase Delay conversion of disaccharides in to monosaccharide
DPP-4 inhibitors
Sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin	Decrease glucagon release Glucose-dependent insulin release Decrease appetite Delay gastric emptying
Sodium–glucose co–transporter 2 (SGLT2) inhibitors
Canagliflozin, dapagliflozin, empagliflozin	Inhibit reabsorption of glucose from proximal convoluted tubules and promote glycosuria

Abbreviations: PPAR-γ, peroxisome proliferator-activated receptor gamma; DPP-4, dipeptidyl peptidase-4.

Table 2 Drawbacks of nonhormonal treatment

Antidiabetic agents	Potential side effects	Limitations to usage
Insulin sensitizers
Biguanides	Gastrointestinal disturbance, lactic acidosis, and B12 deficiency	Chronic kidney diseases, chronic liver diseases, pulmonary insufficiency, and congestive cardiac failure
Thiazolidinedione	Peripheral edema, dilutional anemia, and atypical fractures	Congestive heart failure, renal failure, risk factors of bladder cancer, pregnancy, and lactation
Insulin secretagogues
Sulfonylureas	Allergy, weight gain, and hypoglycemia	Renal failure, hepatic failure, porphyria, pregnancy, and lactation
Non-sulfonylureas	Weight gain and hypoglycemia	Liver diseases, pregnancy, and lactation
Alpha-glucosidase inhibitors	Flatulence, diarrhea, and abdominal pain	Inflammatory bowel disease, renal and liver diseases, pregnancy, and lactation
Dipeptidyl peptidase-4 inhibitors	Nausea, vomiting, diarrhea, nasopharyngitis, and pancreatitis	Hypersensitivity reaction, history of pancreatitis, and renal failure
Sodium–glucose co-transporter 2 inhibitors	Urinary tract infections, genital mycotic infections, polyurea, hypotension, hyperkalemia, increased LDL cholesterol, and cardiovascular side effects	Renal diseases, pregnancy, and lactation

Abbreviation: LDL, low-density lipoprotein.

Table 3 Classification and pharmacokinetic profiles of insulin

Insulin types	Onset	Peak	Duration of action
Conventional insulin
Short-acting regular	30–60 minutes	2 hours	6 hours
Intermediate-acting	2–4 hours	4–6 hours	18 hours
Analogs
Ultra-short-acting
Lispro	5–15 minutes	60 minutes	2 hours
Aspart	5–15 minutes	60 minutes	2 hours
Glulisine	5–15 minutes	60 minutes	2 hours
Long-acting
Glargine	2–4 hours	Not significant	24 hours
Detemir	2–4 hours	Not significant	20 hours