DPP INHIBITORS
An analysis by Dr SK Kapoor
Incretins are gut hormones that are secreted from enteroendocrine cells into the blood within minutes after eating. They enhance insulin release by beta cells. These factors are produced by selective posttranslational modification of proglucagon, a peptide expressed by the α-cells. Produced by K and L cells of the small intestine.
They cause a release of GLP1 and GIP which induces the pancreas to produce more insulin from the beta cells and downregulates the alpha cells.
DPP4 enzyme inhibits the action of GLP1 and GIP.
The INCRETIN EFFECT describes the phenomenon whereby oral glucose elicits higher insulin secretory responses than does intravenous glucose, despite inducing similar levels of glycaemia, in healthy individuals.
The incretin effect is blunted in T2DM. This leads to lipolysis, increased free fatty acids and hypertriglyceridemia. There is associated hyperglucagonemia.
DPP4 INHIBITORS – the gliptins (derived from GL I and P) – block the action of DPP4 and cause a 2-3 times rise of GLP1 and GIP, thereby inducing the pancreas to produce more insulin and inhibit the production of glucagon.
They increase active GLP1in a glucose dependent manner, not seen in any other OAD. Hence they have a LOW RISK OF HYPOGLYCEMIA- a feature very important in the elderly.
LINAGLIPTIN
is the most desirable gliptin and is discussed further.
SUs cause weight gain by ‘defensive snacking’ due to episodes of hypoglycemia. Not seen with Lina..
No adjustment with renal impairment because only 18% is metabolized and excreted by the kidney. 82% is excreted in the faeces.
Higher the HbA1c, the greater is the reduction with linagliptin (and better in the elderly).
They have a good safety and tolerability profile. Side effects include nasopharygitis and bullous pemphigoid.