Peptide 1 similar to glucagon (LPG-1) is a hormone of the incredine group that plays an important role in regulating the postprandial blood glucose level, in a glucose-dependent way.However, its clinical use is not possible, due to the rapid degradation that it suffers from the action of the Dipeptidil peptidase-4 enzyme (DPP-4).Pharmacological inhibition of DPP-4 could clinically help control glycemia levels, both in fasting and postprandial, by increasing the plasma concentration of the LPG-1.
Teneligliptin, a new DPP-4 inhibitor, is mainly metabolizes in the liver and its plasma concentration is not affected by renal failure, which suggests that it can be administered in patients with renal commitment due to diabetic nephropathy, without adjustmentof the dose.This property differentiates the tenigliptin of other DPP-4 inhibitors.On the other hand, various recent studies have shown that teliciptin has a major inhibitory power of DPP-4 than that of other drugs in the group, including saxagliptin, alogliptin, linagliptin and vovoglyptine.
Insulin is the most powerful hypoglycemic agent available for the treatment of patients with type 2 diabetes mellitus (DBT2) without adequate control of their disease.It is known that the treatment combined with insulin and oral antidiabetics is more effective than insulin therapy alone.The advantages of the treatment combined with insulin and with an inhibitor of the DPP-4, such as syliphastin, include improvement in blood glucose control and weight prevention, which can occur with insulin treatment.
Teneligliptin was approved in Japan in 2013 as a drug to be added to treatment with other antidiabetics.To date, there are no studies that have shown the efficacy of the treatment combined with insulin and tenigliptin in patients with DBT2.
In this study, the authors investigated the effects of the aggregate of Teneligliptin to an insulin treatment alone or associated with other antidiabetics.
patients and methods
Study participants were selected among diabetic patients admitted to the Dokkyo Medical University Hospital, in Japan, to achieve the stabilization of blood glucose, with the administration of insulin, alone or associated with another antidiabetic (except DPP-4 inhibitors).The inclusion criteria were age ≥ 20 years, glucosylated hemoglobin (HBA1C) & GT;7.5% to income and treatment with insulin (& lt; 60 IU for at least 2 weeks);Patients could simultaneously receive other oral antidiabetics (except DPP-4 inhibitors).The exclusion criteria covered type 1 diabetes mellitus, serious complications of diabetes, renal failure, liver failure, serious infections, pregnancy, breastfeeding, alcoholism or low probability of therapeutic observance (at the discretion of the researcher).
The investigation was carried out through a pilot, prospective, not masked study, of 26 participants.After achieving the stabilization of blood glucose, with insulin alone or with oral insulin and antidiabetics, in stable doses and with an optimal diet, continuous glycemia monitoring began, for 7 consecutive days.To the fourth day of the monitoring, the tenigliptin was added to the treatment, in a daily dose of 20 mg, after breakfast.As a reflection of the fluctuations of blood glucose in 24 hours, the average levels of blood glucoseHyperglycemia (& GT; 140 mg/dl), the percentages of hypoglycemia (& lt; 70 mg/dl), the area under the curve (ABC) in the 2 hoursafter each meal and postprandial blood glucose at 2 hours.Glycosylated, 1.5-Anhydro-D-Glucitol and C-reactive protein (PCR) high sensitivity (PCR) levels were measured on day 0 (beginning of continuous monitoring), on day 4 and day 8 (end of thestudy).
The data is presented as means ± standard deviation.The differences between the time points were evaluated with the proof of the Wilcoxon sign.A P& LT value was considered significant;0.05.
Results
The group studied was formed by 26 patients (13 men and 13 women; age: 60.8 ± 15.7 years).The most common insulin therapeutic scheme was the application of multiple injectable doses (13 patients, 50%) and the most used antidiabetic was metformin (8 patients, 30.7%).
After the aggregate of 20 mg daily teneligliptin was observed the decrease in blood glucose levels in continuous 24 -hour monitoring.Fasting blood glucose and postprandial blood glucose decreased significantly between days 5 and 7, after the beginning of treatment.The average blood glucose of 24 hours decreased significantly after the aggregate of the tenigliptin (P&R 0.001), as well as the percentage of time in hyperglycemia conditions (P&T 0.001).
On the other hand, there was no difference in the percentage of time in hypoglycemia conditions.The average amplitude of glycemia variations were significantly lower after the start of the Teneligliptin administration (P&R 0.05).Treatment with tenigliptin decreased postprandial blood glucose and total ABC at 2 hours of each intake.Changes in glycemic control rates and inflammatory markers occurred early after the start of tenigliptin.Glycosylated albumin levels decreased significantly and levels of 1.5-anhydro-D-glucitol increased substantially, while high sensitivity PCR was not modified.
In the controls remote over time (at 6 months after the start of the study) and compared to the values prior to the treatment, it was observed that the teliciptin significantly improved the levels of the HBA1C (10.8 ± 2.6% front 7.6 ± 1.6%) andof glucosylated albumin (23.5 ± 6.1% compared to 19.8 ± 3.1%).
Discussion and conclusions
The present study investigated the effects of a new DPP-4 inhibitor (Teneligliptin, in dose of 20 mg per day) on 24-hour blood glucose levels, in patients with DBT2, who received insulin and other oral antidiabetics.Teneligliptin aggregate to treatment significantly improved the 24 -hour glycemia profile and the average amplitude of glycemia variations (estimated through continuous glycemia monitoring), without increasing hypoglycemia events.In previous studies it had been noted that the Sitagliptin administration was associated with descents of glycemia, both postprandial and preprandial.The results with tenigliptin confirm these observations, with the characteristic that the tenigliptin produced these results in a short period.
Several researchers argued that glycemia fluctuations have a superior oxidative stress power superior to prolonged chronic hyperglycemia.The variability of blood glucose can be an important risk factor for the appearance of cardiovascular disease.Teneligliptin showed good control of fluctuations in plasma glucose levels.The results suggest that the treatment combined with insulin and tenigliptin (associated with another oral antidiabetic or without it) can be a beneficial option for the treatment of patients with DBT2, especially if they are elderly patients, with diabetic complications and withcardiovascular disease
Some previous studies showed that another DPP-4 inhibitor, Sitagliptin, decreased high sensitivity PCR levels, which suggests an anti-inflammatory effect.In this study with Teneligliptin, significant variations of the high sensitivity PCR level could not be demonstrated.Researchers do not rule out that the lack of anti -inflammatory effect may be due to the short period of treatment, the small number of patients in the sample or the absence of an adequate control group.
The study had some limitations associated with the fact of being a pilot essay: a small number of participants, absence of a control group and lack of a trial meal.The authors recommend the realization of a large -scale study to confirm the findings.
In conclusion, the present study showed that the aggregate of Teneligliptin decreased the elapsed time in hyperglycemia conditions, time increased in normal blood glucose conditions and significantly improved the fluctuations of blood glucose in 24 hours.Teneligliptin aggregate to treatment can be a beneficial therapeutic option for patients with insulin DBT2, whether they receive another antidiabetic or not.
♦ SIIC - Ibero -American Society of Scientific Information
