EASD: DPP-4 inhibition effects on glycemia and islet hormones in individuals with type 2 diabetes

Published 20 September 2019

Wathik Alsalim presented new findings on persistent whole day meal effects of three DPP-4 inhibitors on incretin- and islet hormones in metformin-treated type 2 diabetes
Learn more about the study:

Wathik Alsalim work as consultant in the Diabetes and Endocrinology Department at Skåne University Hospital, SUS, in Lund.

- Since I was at university, I was interested in diabetes because it has been a major problem in my original country Iraq.

He has presented many posters at EASD before, but this was his first oral presentation.

Can you describe your findings?

- Meal ingestion stimulates gut endocrine cell to release incretin hormones, glucagon-like-peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP). These two hormones in turn stimulate insulin secretion to suppress the rise of glucose after meal ingestion.

Both GLP-1 and GIP undergo rapid degradations by dipeptidyl peptidase-4 (DPP-4) into inactive form of GLP-1 and GIP.

Several DPP-4 inhibitors has been existing in oral therapy in the treatment of subjects with type 2 diabetes since 2006. However, most of the studies on the mechanism of DPP-4 inhibitors have been undertaken after a single meal or oral glucose tolerance test. Therefore, it is still not established whether the effects of DPP-4 inhibition persist after meal ingestion over the whole day, and whether various DPP-4 inhibitors differ from each other in their effect over the day. Therefore, we aimed in this project to examine the whole day effects of DPP-4 inhibition in subjects treated initially with metformin and were well-controlled type 2 diabetes, and we evaluated the glucose, beta-cell function ( insulin producing cells), glucagon and incretin hormones in these subjects. The second aim of the study was to examine the different DPP-4 inhibitors mechanism of action. We included in this study the three most commonly used in DPP-4 inhibitors in clinical practice, sitagliptin 100mg q.d, ( Januvia®), vildagliptin 50mg b.i.d, (Galvus®), and saxagliptin 5mg q.d, (Onglyza®). We also we used placebo in all groups for better comparison in this study.

Twenty four subjects were included in this study between 60 and 70 years old, and their mean HbA1c was 44 mmol/mol.

Each subject underwent four different visits in clinical research center in Lund. After overnight fasting the study medication was given, followed by ingestion of a standardized breakfast, (521kcal), lunch (780kcal) and dinner (560kcal)

In the present study we found that the effect of acute single dose of DPP-4 inhibitors were persist over the whole day and induced a reduction of glucose, stimulation of insulin secretion, suppression of glucagon , augmenting of the active- and suppression of the secretion of incretin hormones.

Based on these results our conclusion are that DPP-4 inhibition throughout the day induces:

Persistent effects
Prolonged elevation of active incretin hormones, which in turn induces a feedback suppression of incretin hormone secretion
Suppression of glucagon, which could be of importance to control glycemia

DPP-4 inhibition as add-on to metformin has effects on glycemia and islet hormones in subjects with well-controlled type 2 diabetes.

The choice of DPP-4 inhibitors is not critical in regard to their glucose-suppression effects.

What are you looking forward to the most during the conference?

- I’m looking forward to meet my colleagues from all over the world to share and discuss our knowledge and experience about how to make diabetes management better.