Journal of Renal Nutrition and Metabolism Vol 2 No 2 April- June 2016 Editorial I

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Gleptins


Incretins are a group of metabolic hormones which decrease blood glucose levels. Incretins act i) by increasing the amount of insulin released from pancreatic beta cells after meal, before blood glucose levels become elevated and ii) by slowing the rate of absorption of nutrients into the blood stream.The rate of absorption of nutrients is achieved by reducing gastric emptying and that also directly reduces food intake1. The incretin effect is defined as the "increased stimulation of insulin secretion elicited by oral as compared with intravenous administration of glucose under similar plasma glucose levels''. Incretins inhibit release of glucagon from the alpha cells of the islets of Langerhans 1.

Glucagon-like peptide (GLP)-1 is a gut hormone (secreted by K cells) that stimulates insulin secretion and P-cell growth. GLP-1 acts with hormone glucose-dependent insulinotropic polypeptide (GIP, secreted by L cells in the gut), and is responsible for the incretin effect, the augmentation of insulin secretion after oral intake2. Patients with type 2 diabetes mellitus have little or no incretin-mediated augmentation of insulin secretion.This is because of decreased secretion of GLP-1 and loss of the insulinotropic effects of GIP. GLP-1, however, retains insulinotropic effects, and the hormone effectively improves metabolism in patients with type 2 diabetes.Studies have shown that continuous subcutaneous administration, improves glucose profile, insulin resistance and P-cell performance and reduces body weight, HbAlc and free fatty acids3. Hence, deficient incretin function may play an essential contributory role in the pathogenesis of type 2 diabetes. It has been proposed that deficient incretin effect is due to impaired secretion of the incretin hormones aswell asto impaired effects on function of islet of Langerhans.

Diabetes is an important risk factor for chronic kidney disease (CKD). The treatment of hypoglycaemia in diabetic persons with CKD is challenging and the problem is complicated by the fact that in many efficacy studies patients with CKD are excluded so data of safety and efficacy for these patients are missing. Hypoglycemia is a major issue in maintain tight control of blood glucose in CKD. Drugs which are emerging useful for this group of patients are dipeptidyl peptidase 4 inhibitors.

In this issue, a retrospective study analyzes outcome of patients with T2DM and CKD in whom gliptin (saxagliptin, sitagliptin, vildagliptin and linagliptin) was introduced at as an oral hypoglycemic agent with reduction of insulin and/or secretogogue. The first Indian study analysed efficacy and safety of gliptins in patients with T2DM and CKD stage 3 to 5 through self monitoring of blood glucose level and HbAlc level. The patients were on insulin and/or secretogogue which was reduced with introduction of gliptin.Gliptins were well tolerated with no severe adverse effect. Renal function was stable. The results showed that after 6 months of intervention, mean HBAlc decreased from 8.1±1.4 to 7.9 ±1.5, body weight decreased from 72.3 ±10.6 kg to 71.9±10.9 kg and creatinine clearance declined from 29 ± 12 ml/min to 28 ±13 ml/min but differences was not statistically significant (p>0.05). The study demonstrates that gliptins provide clinically useful glycemic control in patients with T2 DM and CKD, with no adverse effect on renal function and bodyweight.


References

  1. Drucker DJ, Nauck MA (November 2006). The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes". Lancet. 368 (9548): 1696-705.

  2. Amori RE, Lau J, Pittas AG (July 2007). Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta­ analysis.JAMA. 298 (2):194-206

  3. Rang & Dale's Pharmacology, 8th Edition 2015 Editors HP Rang, JM Ritter, RJ Flower and G Handerson Elsevier