Dataset Information

Effects of Vildagliptin or Pioglitazone on Glycemic Variability and Oxidative Stress in Patients with Type 2 Diabetes Inadequately Controlled with Metformin Monotherapy: A 16-Week, Randomised, Open Label, Pilot Study.

ABSTRACT:

Background

Glycemic variability is associated with the development of diabetic complications through the activation of oxidative stress. This study aimed to evaluate the effects of a dipeptidyl peptidase 4 inhibitor, vildagliptin, or a thiazolidinedione, pioglitazone, on glycemic variability and oxidative stress in patients with type 2 diabetes.

Methods

In this open label, randomised, active-controlled, pilot trial, individuals who were inadequately controlled with metformin monotherapy were assigned to either vildagliptin (50 mg twice daily, n=17) or pioglitazone (15 mg once daily, n=14) treatment groups for 16 weeks. Glycemic variability was assessed by calculating the mean amplitude of glycemic excursions (MAGE), which was obtained from continuous glucose monitoring. Urinary 8-iso prostaglandin F₂α, serum oxidised low density lipoprotein, and high-sensitivity C-reactive protein were used as markers of oxidative stress or inflammation.

Results

Both vildagliptin and pioglitazone significantly reduced glycated hemoglobin and mean plasma glucose levels during the 16-week treatment. Vildagliptin also significantly reduced the MAGE (from 93.8±38.0 to 70.8±19.2 mg/dL, P=0.046), and mean standard deviation of 24 hours glucose (from 38±17.3 to 27.7±6.9, P=0.026); however, pioglitazone did not, although the magnitude of decline was similar in both groups. Markers of oxidative stress or inflammation including urinary 8-iso prostaglandin F₂α did not change after treatment in both groups.

Conclusion

In this 16-week treatment trial, vildagliptin, but not pioglitazone, reduced glycemic variability in individuals with type 2 diabetes who was inadequately controlled with metformin monotherapy, although a reduction of oxidative stress markers was not observed.

SUBMITTER: Kim NH

PROVIDER: S-EPMC5503869 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Publications

Effects of Vildagliptin or Pioglitazone on Glycemic Variability and Oxidative Stress in Patients with Type 2 Diabetes Inadequately Controlled with Metformin Monotherapy: A 16-Week, Randomised, Open Label, Pilot Study.

Kim Nam Hoon NH Kim Dong Lim DL Kim Kyeong Jin KJ Kim Nan Hee NH Choi Kyung Mook KM Baik Sei Hyun SH Kim Sin Gon SG

Endocrinology and metabolism (Seoul, Korea) 20170601 2

<h4>Background</h4>Glycemic variability is associated with the development of diabetic complications through the activation of oxidative stress. This study aimed to evaluate the effects of a dipeptidyl peptidase 4 inhibitor, vildagliptin, or a thiazolidinedione, pioglitazone, on glycemic variability and oxidative stress in patients with type 2 diabetes.<h4>Methods</h4>In this open label, randomised, active-controlled, pilot trial, individuals who were inadequately controlled with metformin monot ...[more]

PMID: 28685513

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Project description:BackgroundAcarbose and repaglinide are widely used either by themselves or in combination with other medications. However, their efficacy in diabetes control has not been compared when used in combination with metformin.MethodsThe present study aimed to compare their effects on glycemic variability (GV) control when taken with metformin for type 2 diabetes mellitus (T2DM) inadequately controlled with metformin alone. In this retrospective cohort study, T2DM patients who were treated with either acarbose-metformin or repaglinide-metformin combination were recruited. Either acarbose 100 mg or repaglinide 2 mg triple daily was taken for the subsequent 12 weeks in combination with metformin. Demographic data, biochemical data and 7-point glycemic self-monitoring conducted with capillary blood (SMBG) data were reviewed after one week and 12 weeks. The primary outcome including glucose control and changes in GV as well as other factors affecting GV and the incidence of hypoglycemia were also analyzed.ResultsOf the 305 T2DM patients enrolled, data from 273 subjects, 136 in the acarbose-metformin group (M+A) and 137 in the repaglinide-metformin group (M+R) were analyzed. Both regimens improved glycemic control at 12 weeks post commencement of new medications. GV, expressed as the mean amplitude of plasma glycemic excursions (MAGE, 5.0 ± 2.6 vs. 2.8 ± 1.6 mmol/L, p < 0.001 in M+A; 5.1 ± 2.5 vs. 2.9 ± 1.3 mmol/L, p < 0.001 in M+R), standard deviation of blood glucose (SDBG, 3.6 ± 1.3 vs. 2.0 ± 0.9 mmol/L, p < 0.001 in M+A; 3.7 ± 1.3 vs. 2.4 ± 1.3 p < 0.001 in M+R), coefficient of variation of blood glucose (CVBG, (0.30 ± 0.09 vs. 0.21 ± 0.1, p < 0.001 in M+A; 0.31 ± 0.09 vs. 0.24 ± 0.12, p < 0.001 in M+R), postprandial amplitude of glycemic excursions (PPGE, 5.2 ± 2.6 vs. 2.8 ± 1.6 mmol/L, p < 0.001 in M+A; 5.3 ± 2.5 vs. 2.9 ± 1.3 mmol/L, p < 0.001 in M+R) or largest amplitude of glycemic excursions (LAGE, 9.8 ± 3.6 vs. 5.4 ± 2.4 mmol/L, p < 0.001 in M+A; 10.1 ± 3.4 vs. 6.3 ± 3.2 mmol/L, p < 0.001 in M+R) decreased significantly after the addition of acarbose or repaglinide (p < 0.05 respectively). Compared with repaglinide-metformin, acarbose-metformin was more effective in GV control at 12 weeks post commencement of new medications (p < 0.05). This study indicates that both acarbose-metformin and repaglinide-metformin combinations could effectively reduce GV and the acarbose-metformin combination seems to be more effective than the repaglinide-metformin combination. However, this conclusion should be confirmed by future large-scaled and more comprehensive studies due to the limitations of the present study.

Project description:IntroductionA slower adoption rate of fixed dose combinations (FDC) in diabetes management is partly due to insufficient data. This study evaluates the safety and efficacy of an FDC of dapagliflozin + sitagliptin + metformin hydrochloride extended release (XR), compared to a dual FDC of sitagliptin + metformin hydrochloride XR among patients with type 2 diabetes mellitus (T2DM) with poor glycemic control when treated with metformin monotherapy.MethodsA total of 274 patients with T2DM were randomized (1:1) to either arm X, receiving FDC of dapagliflozin (10 mg) + sitagliptin (100 mg) + metformin hydrochloride XR (1000 mg) (Dapa + Sita + Met) tablets, or arm Y, receiving sitagliptin phosphate (100 mg) + metformin hydrochloride XR (1000 mg) (Sita + Met) tablets, and treated for 16 weeks. The outcome measures included changes in hemoglobin A1c (HbA1c)(%), fasting plasma glucose (FPG), 2-h post-prandial glucose (PPG), weight, and the proportion of patients achieving target HbA1c levels of < 7.0% by week 16 of the study period.ResultsThe reduction in HbA1c at week 16 was significantly higher in arm X than in arm Y [estimated treatment difference (ETD), - 0.65% (95% CI - 0.76 to - 0.53; P < 0.0001)]. Arm X showed a marked decrease in FPG [ETD - 15.42 mg/dl; 95% CI (17.63, 13.22; P < 0.0001)], PPG [ETD - 30.39 mg/dl; 95% CI (35.59, 25.19; P < 0.0001)], and weight [ETD - 1.47 kg; 95% CI (1.59, 1.28; P < 0.0001)] after 16 weeks. In arm X, 54% of patients reached HbA1c < 7.0% compared to 29.9% in arm Y. The incidence of adverse events was comparable [13.14% (arm X) vs 12.4% (arm Y)]. There was no severe hypoglycemia-led treatment discontinuation.ConclusionAmong patients with T2DM who have poor glycemic control with metformin monotherapy, triple FDC (Dapa + Sita + Met) effectively helped achieve better glycemic response compared to dual FDC (Sita + Met), with a comparable safety and tolerability profile.Trial registrationCTRI/2022/01/039857.

Project description:IntroductionTo compare blood glucose variability (GV) in Chinese participants with type 2 diabetes mellitus (T2DM) whose blood glucose levels are inadequately controlled with metformin monotherapy after twice-daily exenatide or biphasic insulin aspart 30 (BIAsp30).MethodsIn this 16-week multicenter, randomized clinical trial, 104 participants were randomized 1:1 to receive exenatide (exenatide group) or BIAsp30 (BIAsp30 group) twice daily. All participants continued metformin treatment. The primary outcome was the change in GV as measured by a continuous glucose monitoring system (CGMS) from baseline to 16 weeks.ResultsAt 16 weeks, both the Exenatide and BIAsp30 groups effectively decreased mean glucose (MG), but neither group changed the mean amplitude of glycemic excursion (MAGE), largest amplitude of glycemic excursion (LAGE), mean of daily difference (MODD), or standard deviation of blood glucose (SDBG). The decrease in 2-h post-breakfast glucose excursions was greater in the Exenatide group compared to the BIAsp30 group, with a least square (LS) mean difference [95% CI] of (1.58 [0.53, 2.63]). Exenatide also significantly reduced 2-h post-lunch glucose excursion compared to BIAsp30 (LS mean difference [95% CI], 1.19 [0.18, 2.20]). The Exenatide group had significantly reduced body weight and body mass index (BMI), while the BIAsp30 group had increased weight and had no change in BMI. Both treatments were well tolerated with no serious hypoglycemic events and with fewer identified hypoglycemic events in the Exenatide group than in the BIAsp30 group (5.77% vs. 17.31%, P < 0.01).ConclusionAlthough there was no difference in change of GV between Exenatide and BIAsp30, exenatide provided more improvement in postprandial glucose excursion and weight control, without increasing the risk of hypoglycemia in Chinese patients with T2DM whose blood glucose was inadequately controlled with metformin. These findings may provide new options for patients who choose further hypoglycemic treatment, especially in patients with obesity who have large postprandial plasma glucose excursions.Trial registrationClinicalTrials.gov indentifier: NCT02449603.

Project description:BackgroundManagement of type 2 diabetes with metformin often does not provide adequate glycemic control, thereby necessitating add-on treatment. In a 24-week clinical trial, dapagliflozin, an investigational sodium glucose cotransporter 2 inhibitor, improved glycemic control in patients inadequately controlled with metformin. The present study is an extension that was undertaken to evaluate dapagliflozin as long-term therapy in this population.MethodsThis was a long-term extension (total 102 weeks) of a 24-week phase 3, multicenter, randomized, placebo-controlled, double-blind, parallel-group trial. Patients were randomly assigned (1:1:1:1) to blinded daily treatment (placebo, or dapagliflozin 2.5 to 5, or 10 mg) plus open-label metformin (≥1,500 mg). The previously published primary endpoint was change from baseline in glycated hemoglobin (HbA1c) at 24 weeks. This paper reports the follow-up to week 102, with analysis of covariance model performed at 24 weeks with last observation carried forward; a repeated measures analysis was utilized to evaluate changes from baseline in HbA1c, fasting plasma glucose (FPG), and weight.ResultsA total of 546 patients were randomized to 1 of the 4 treatments. The completion rate for the 78-week double-blind extension period was lower for the placebo group (63.5%) than for the dapagliflozin groups (68.3% to 79.8%). At week 102, mean changes from baseline HbA1c (8.06%) were +0.02% for placebo compared with -0.48% (P = 0.0008), -0.58% (P <0.0001), and -0.78% (P <0.0001) for dapagliflozin 2.5 to 5, and 10 mg, respectively. In addition, all dapagliflozin groups had sustained reductions from baseline in FPG (-1.07 to -1.47 mmol/l) and body weight (-1.10 to -1.74 kg) at 102 weeks, whereas increases were noted in placebo-treated patients for both of these outcomes. Events of hypoglycemia were rare and were not severe. Evidence suggestive of genital infection was reported in 11.7% to 14.6% of dapagliflozin patients and 5.1% of placebo patients, with one related discontinuation (dapagliflozin 5 mg). Evidence suggestive of urinary tract infection was reported in 8.0% to 13.3% of dapagliflozin patients and 8.0% of placebo patients, with one related discontinuation (dapagliflozin 2.5 mg).ConclusionsDapagliflozin added to metformin for 102 weeks enabled sustained reductions in HbA1c, FPG, and weight without increased risk of hypoglycemia in patients with type 2 diabetes who were inadequately controlled on metformin alone.Trial registrationClinicalTrials.gov: NCT00528879.

Dataset Information

Effects of Vildagliptin or Pioglitazone on Glycemic Variability and Oxidative Stress in Patients with Type 2 Diabetes Inadequately Controlled with Metformin Monotherapy: A 16-Week, Randomised, Open Label, Pilot Study.

Background

Methods

Results

Conclusion

Publications

Effects of Vildagliptin or Pioglitazone on Glycemic Variability and Oxidative Stress in Patients with Type 2 Diabetes Inadequately Controlled with Metformin Monotherapy: A 16-Week, Randomised, Open Label, Pilot Study.

Similar Datasets

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