Persistent whole day meal effects of three dipeptidyl peptidase‐4 inhibitors on glycaemia and hormonal responses in metformin‐treated type 2 diabetes

Abstract

Aim Dipeptidyl peptidase‐4 (DPP‐4) inhibition has effects on both fasting and postprandial glucose. However, the extent of this effect over the whole day and whether different DPP‐4 inhibitors have the same effects have not been established. We therefore explored the whole day effects of three different DPP‐4 inhibitors versus placebo on glucose, islet and incretin hormones after ingestion of breakfast, lunch and dinner in subjects with metformin‐treated and well‐controlled type 2 diabetes. Methods The study was single‐centre and crossover designed, involving 24 subjects [12 men, 12 women, mean age 63 years, body mass index 31.0 kg/m2, glycated haemoglobin 44.7 mmol/mol (6.2%)], who underwent four test days in random order. Each whole day test included ingestion of standardized breakfast (525 kcal), lunch (780 kcal) and dinner (560 kcal) after intake of sitagliptin (100 mg) or vildagliptin (50 mg twice), or saxagliptin (5 mg) or placebo. Results Compared with placebo, DPP‐4 inhibition reduced glucose levels, increased beta‐cell function (insulin secretory rate in relation to glucose), suppressed glucagon, increased intact glucagon‐like‐peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) but suppressed total GLP‐1 and GIP after all three meals. The effects were sustained throughout the daytime period with similar changes after each meal and did not differ between the DPP‐4 inhibitors. Conclusions DPP‐4 inhibition has persistent daytime effects on glucose, islet and incretin hormones with no difference between three different DPP‐4 inhibitors.

Diabetes Mellitus: Disorder of Cellular Dysfunction Due to Lack of Entry into Cell of Glucose. The Most Efficient Fuel for Cellular Function*

“…The hypothesis is also consistent with available data in literature documenting lowering of plasma glucagon and rise in insulin directly as well as via increase in GLP1 and GIP concentrations on improvement in insulin sensitivity following treatment with insulin sensitizers e.g. metformin or glitazones in type 2 diabetes and by insulin administration in both type 1 and type 2 diabetes [39]- [47]. Finally, alteration of other pancreatic hormones, e. g. amylin, pancreastatin, somatostatin as well as pancreatic polypeptide are documented in both type 1 and type 2 diabetes and may be secondary to dysfunction of other pancreatic endocrine cells due to lack of glucose entry by the same aforementioned mechanism [48] [49] [50].…”

Role of dipeptidyl peptidase 4 inhibitors in the new era of antidiabetic treatment

“…The frail elderly population may also benefit due to the low risk of hypoglycemia with DPP-4 inhibitors. Post-hoc analysis of the SAVOR-TIMI 53 data established the safety and efficacy of saxagliptin in the elderly[ 58 ], an observation that has been confirmed by other studies of DPP-4 inhibitors in this patient population[ 59 , 60 ]. We should stress that saxagliptin is contraindicated in patients with HF due to the increased risk of hospitalizations for HF associated with its use[ 47 ].…”

Evaluation of Hypoglycaemic Effects of Dipeptidyl Peptidase–4 Inhibitors and Biguanide on Type-2 Diabetic subjects: A six months trial

“…Alogliptin that affects improving insulin resistance when used in dual therapy with another hypoglycemic agent. [29][30][31] Dipeptidyl Peptidase-4 is a class of drugs that reduces the inactivation of GLP-1 and GIP which increases the synthesis of insulin and decreases glucagon release by pancreatic cells. Glycemic effectiveness is achieved when both DPP-4 and biguanide are used together.…”