The Place of Dipeptidyl Peptidase-4 Inhibitors in Type 2 Diabetes Therapeutics: A “Me Too” or “the Special One” Antidiabetic Class?
Table 1
Main features of non-incretin-based antidiabetic drugs for T2DM treatment.
Class
Mechanisms of action
Effects/advantages
Adverse reactions
ΔHbA1c (−%)
Biguanides
Decrease hepatic glucose production and gluconeogenesis Decrease intestinal glucose absorption Increase peripheral glucose utilization
Reduce blood glucose levels in hyperglycaemic state only Reduce lipid levels Cause modest reduction of body weight Perform oral administration
Nausea and vomiting Diarrhoea Lactic acidosis
1.0–2.0
Sulfonylureas
Increase pancreatic insulin secretion Decrease or unchanged plasma insulin levels
Reduce blood glucose levels in hyperglycaemic and normoglycemic states Increase plasma insulin levels Perform oral administration
Increased body weight Hypoglycaemia Nausea and vomiting
1.0–2.0
Thiazolidinediones
Decrease hepatic glucose production and gluconeogenesis Increase peripheral glucose utilization
Reduce blood glucose levels in hyperglycaemic state only Reduce lipid levels (triglycerides) Have possible benefits on cardiovascular risk factors Perform oral administration
Increased body weight Anaemia Oedema Congestive heart failure in susceptible individuals
0.5–1.4
Meglitinides
Increase pancreatic insulin secretion
Reduce blood glucose levels in hyperglycaemic and normoglycemic states Reduce postprandial glucose excursions Have no significant effects on lipid levels Perform oral administration
Hypoglycaemia Increased body weight Diarrhoea
0.5–1.5
α-glucosidase inhibitors
Perform reversible inhibition of α-glucosidase enzymes Decrease digestion of complex carbohydrates Delay glucose absorption
Reduce blood glucose levels in hyperglycaemic state only Have no significant effects on lipid levels Have no effects on body weight Perform oral administration
Abdominal pain Elevation of liver enzymes Diarrhoea
0.5–0.8
Sodium-glucose cotransporter 2 inhibitors
Perform inhibition of renal reabsorption of glucose, thus increasing urinary glucose excretion
Reduce plasma glucose Have beneficial effects on body weight and blood pressure Have low risk of hypoglycaemia
Risk of urinary and genital tract infections Requirement of regular monitoring of renal function and kalemia
0.5–0.8
Insulin
Replace endogenous insulin
Reduce blood glucose levels in hyperglycaemic and normoglycemic states Perform subcutaneous administration
