scholarly journals TriMaster: randomised double-blind crossover study of a DPP4 inhibitor, SGLT2 inhibitor and thiazolidinedione as second-line or third-line therapy in patients with type 2 diabetes who have suboptimal glycaemic control on metformin treatment with or without a sulfonylurea—a MASTERMIND study protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e042784
Author(s):  
Catherine Angwin ◽  
Caroline Jenkinson ◽  
Angus Jones ◽  
Christopher Jennison ◽  
William Henley ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Side Effects ◽  
Crossover Trial ◽  
Treatment Options ◽  
Sglt2 Inhibitor ◽  
Oral Glucose ◽  
Double Blind ◽  
Glucose Lowering ◽  
South Central

IntroductionPharmaceutical treatment options for patients with type 2 diabetes mellitus (T2DM) have increased to include multiple classes of oral glucose-lowering agents but without accompanying guidance on which of these may most benefit individual patients. Clinicians lack information for treatment intensification after first-line metformin therapy. Stratifying patients by simple clinical characteristics may improve care by targeting treatment options to those in whom they are most effective. This academically designed and run three-way crossover trial aims to test a stratification approach using three standard oral glucose-lowering agents.Methods and analysisTriMaster is a randomised, double-blind, crossover trial taking place at up to 25 clinical sites across England, Scotland and Wales. 520 patients with T2DM treated with either metformin alone, or metformin and a sulfonylurea who have glycated haemoglobin (HbA1c) >58 mmol/mol will be randomised to receive 16 weeks each of a dipeptidyl peptidase‐4 inhibitor, sodium-glucose co-transporter-2 inhibitor and thiazolidinedione in random order. Participants will be assessed at the end of each treatment period, providing clinical and biochemical data, and their experience of side effects. Participant preference will be assessed on completion of all three treatments. The primary endpoint is HbA1c after 4 months of therapy (allowing a range of 12–18 weeks for analysis). Secondary endpoints include participant-reported preference between the three treatments, tolerability and prevalence of side effects.Ethical approvalThis study was approved by National Health Service Health Research Authority Research Ethics Committee South Central—Oxford A, study 16/SC/0147. Written informed consent will be obtained from all participants. Results will be submitted to a peer-reviewed journal and presented at relevant scientific meetings. A lay summary of results will be made available to all participants.Trial registration numbers12039221; 2015-002790-38 and NCT02653209.

scholarly journals Effects of the SGLT2 Inhibitor Dapagliflozin on Energy Metabolism in Patients With Type 2 Diabetes: A Randomized, Double-Blind Crossover Trial

Diabetes Care ◽  
2021 ◽  
pp. dc202887
Author(s):  
Yvo J.M. Op den Kamp ◽  
Marlies de Ligt ◽  
Bas Dautzenberg ◽  
Esther Kornips ◽  
Russell Esterline ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Energy Metabolism ◽  
Crossover Trial ◽  
Sglt2 Inhibitor ◽  
Double Blind

Abstract 16844: Effect of Canagliflozin on Gene Expression and CD34+ Function on Type 2 Diabetes Subjects

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Hassan Awal ◽  
Seshagiri Rao Nandula ◽  
Nabanita KUNDU ◽  
Mona Fakhri ◽  
Beda Brichacek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Mixed Model ◽  
Cell Function ◽  
Sglt2 Inhibitor ◽  
P Value ◽  
Vegf Receptor ◽  
Double Blind ◽  
Endothelial Cell Function

Introduction: CD34 +ve Endothelial progenitor cells (EPCs) has been shown to be dysfunctional in subjects with type 2 diabetes mellitus (T2DM) leading to poor endothelial cell function (ECF). Hypothesis: Canagliflozin, an SGLT2 inhibitor when added to other oral antidiabetic medication such Metformin, Insulin, GLP1-agonists, DPP-IV inhibitor, or sulfonylureas, may improve the cardiovascular risk by improving CD34+ EPCs function such as migration, colony formation and maturation towards endothelium. Methods: 29 subjects were enrolled in this 16 weeks, double-blind, two-arm, randomized placebo matched trial, with 100 mg Canagliflozin (Cana, low dose) compared to placebo. T2DM (30-70 years old), HbA1c of 6.5-10%, and all stages of CKD were included. Peripheral blood derived CD34+ cell number, migratory function, mRNA gene expression along with cardiometabolic parameters such as arterial stiffness, biochemistry, resting energy expenditure, and body composition were measured. Data were collected at weeks 0, 8, and 16. A mixed model regression analysis was done with a p-value <0.05 considered significant. Results: We found a statistically significant reduction in systolic (p=0.008) and diastolic (p=0.038) blood pressure. There was a reduction in blood glucose level (p=0.0047) and HbA1c (p=0.03). There was a statistically significant increase in adiponectin (p=0.0062) and trend level reduction in IL6 (p=0.16), indicating an anti-inflammatory effect of canagliflozin. There is also an increase in mRNA expression of genes associated with endothelial function in CD34+ cells such as VEGFA (p=0.049), VEGF receptor KDR (p=0.13), PECAM-1, a mature endothelial marker was also upregulated (p=0.002) and NOS3 (or eNOS) was also upregulated. There were no significant changes in CD34+ numbers by direct counting and parameters tested. We also tested for serum ketones bodies and found no difference at the dose tested. Data on urine podocyte specific exosome is pending Conclusions: Our study indicates that Canagliflozin improves several components of ECF by improving adiponectin, reducing inflammatory cytokines, and by increasing expression of endothelium specific genes.

scholarly journals P1028EFFECTS OF CANAGLIFLOZIN ON MAJOR ADVERSE CARDIOVASCULAR OUTCOMES IN PATIENTS WITH DIFFERENT BASELINE LEVELS OF TYPE 2 DIABETES MELLITUS DISEASE SEVERITY: RESULTS FROM THE CANVAS PROGRAM

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Tamara Young ◽  
Jing-wei Li ◽  
Amy Kang ◽  
Hiddo Heerspink ◽  
Carinna Hockham ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Disease Severity ◽  
Cardiovascular Outcomes ◽  
Oral Glucose ◽  
Glucose Lowering ◽  
Duration Of Diabetes ◽  
Event Rates

Abstract Background and Aims Patient with type 2 diabetes mellitus (T2DM) included in trials of sodium-glucose cotransporter 2 inhibitors are heterogeneous in terms of disease severity. We assessed the effects of canagliflozin compared to placebo on cardiovascular and renal outcomes in the CANVAS program according to severity of T2DM as indicated by intensity of treatment, duration of diabetes and glycaemic control. Method We compared effects on major adverse cardiovascular events ([MACE], defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) according to three indicators of T2DM severity at study baseline: number of oral glucose lowering treatments or insulin therapy (0-1, 2, 3+, insulin), duration of diabetes (&lt;10, 10-16, &gt;16 years) and HbA1c (&lt;7.0, 7.0-7.5, 7.5-8.0, 8.0-8.5, 8.5-9, &gt;9.0%). We also assessed effects on other pre-specified cardiovascular outcomes, and an adjudicated composite of end-stage kidney disease, renal death or sustained 40% decline in estimated glomerular filtration rate. We assessed for constancy of hazard ratios across subgroups by fitting an interaction term that tested for linear trend. Results Of 10,142 participants in the CANVAS Program, 1011 experienced a MACE during a mean follow-up of 3.6 years. Event rates for MACE were higher in those with longer duration of diabetes and higher HbA1c at baseline. The effect of canagliflozin on MACE in the overall population (HR 0.86, 95 % CI 0.75-0.97) was consistent irrespective of the number of glucose lowering treatments (p=0.509), duration of diabetes (p=0.174) and baseline HbA1c (p =0.314). Effects were also consistent across different levels of T2DM disease severity for all other outcomes studied. Conclusion Higher event rates were observed in those with longer disease duration and higher HbA1c. The proportional risk reductions achieved with canagliflozin were comparable regardless of diabetes duration, number of therapies or HbA1C at baseline.

scholarly journals Cardiovascular safety of linagliptin compared with other oral glucose‐lowering agents in patients with type 2 diabetes: A sequential monitoring programme in routine care

2019 ◽  
Vol 21 (8) ◽  
pp. 1824-1836 ◽  
Author(s):  
Elisabetta Patorno ◽  
Chandrasekar Gopalakrishnan ◽  
Kimberly G. Brodovicz ◽  
Andrea Meyers ◽  
Dorothee B. Bartels ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Routine Care ◽  
Monitoring Programme ◽  
Oral Glucose ◽  
Cardiovascular Safety ◽  
Glucose Lowering

scholarly journals Effects of vitamin K2 supplementation on atherogenic status of individuals with type 2 diabetes: a randomized controlled trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fatemeh Rahimi Sakak ◽  
Nazanin Moslehi ◽  
Hengameh Abdi ◽  
Parvin Mirmiran
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Controlled Trial ◽  
Resistance Index ◽  
Vitamin K2 ◽  
Atherogenic Index ◽  
Oral Glucose ◽  
Double Blind ◽  
Daily Intakes

Abstract Background This study was aimed to examine the effects of vitamin K2 supplementation on atherogenic status, assessed by insulin resistance (IR)-related indexes, in patients with type 2 diabetes mellitus (T2DM). Methods In this double-blind, controlled trial, 68 patients with T2DM on the oral glucose-lowering medications were randomly allocated into two groups receiving daily intakes of 360 μg MK-7 or placebo for 12 weeks. Eight different IR-related indexes were calculated at the baseline and end of the trial. Results At the end of the study, atherogenic coefficient (mean ± SD: − 0.21 ± 0.45 vs. 0.02 ± 0.43; p = 0.043), triglyceride-glucose index (8.88 ± 0.55 vs. 9.23 ± 0.69; p = 0.029), and atherogenic index of plasma (0.37 ± 0.27 vs. 0.51 ± 0.24; p = 0.031) were significantly lower in the vitamin K2 group, compared to the placebo. However, after accounting for their baseline values, the differences were no more significant. No significant differences were observed in Castelli’s Ӏ and ӀӀ risk indexes, the ratio of triglycerides to high-density lipoprotein cholesterol, lipoprotein combine index, and the metabolic score for insulin resistance index between the two groups at the end of the study. Conclusions Daily intakes of 360 μg vitamin K2 in the form of MK-7 for 12 weeks could not improve the IR-related indexes of Cardiovascular Diseases risk. Trial registration The trial was registered on Iranian Registry of Clinical Trials registry (Trial ID. IRCT20190824044592N1) on 22 December 2019. The record can be found at https://en.irct.ir/trial/41728.

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