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- Smits, Mark M., et al.
(author)
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Biliary effects of liraglutide and sitagliptin, a 12-week randomized placebo-controlled trial in type 2 diabetes patients
- 2016
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In: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 18, s. 1217-1225
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Journal article (peer-reviewed)abstract
- © 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. Aims: Treatment with glucagon-like peptide (GLP)-1 receptor agonists or dipeptidyl peptidase (DPP)-4 inhibitors might increase gallstone formation; however, the mechanisms involved are unknown. We aimed to assess the effects of these drugs on gallbladder volume and bile acid profile. Materials and methods: A total of 57 type 2 diabetes patients (mean ± SD age, 62.8 ± 6.9 years; BMI, 31.8 ± 4.1 kg/m2; HbA1c, 7.3% ± 0.6%), treated with metformin and/or sulfonylureas, were included in this 12-week randomized, placebo-controlled, double-blind, single-centre trial between July 2013 and August 2015 at the VU University Medical Center, the Netherlands. Patients received the GLP-1 receptor agonist liraglutide, the DPP-4 inhibitor sitagliptin or matching placebo for 12 weeks. Gallbladder fasting volume and ejection fraction were measured using ultrasonography after a high-fat meal. Serum bile acids were measured in the fasting and postprandial state and in faecal samples. The trial was registered at ClinicalTrials.gov (NCT01744236). Results: Neither liraglutide nor sitagliptin had an effect on gallbladder fasting volume and ejection fraction (p >.05). Liraglutide increased serum levels of deoxycholic acid in the fasting state [0.20 µmol/L (95% CI 0.027-0.376), p = 0.024] and postprandial state [AUC 40.71 (13.22-68.21), p = 0.005] and in faeces [ratio 1.5 (1.03-2.19); p = 0.035]. Sitagliptin had no effect on serum bile acids, but increased faecal levels of chenodeoxycholic acid [ratio 3.42 (1.33-8.79), p = 0.012], cholic acid [ratio 3.32 (1.26-8.87), p = 0.017] and ursodeoxycholic acid [ratio 3.81 (1.44-10.14), p = 0.008]. Conclusions: Neither liraglutide nor sitagliptin has an effect on gallbladder volume. Observed changes in bile acids with liraglutide suggest alterations in the intestinal microbiome, while sitagliptin appears to increase hepatic bile acid production.
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| 2. |
- van Raalte, Daniël H, et al.
(author)
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The effect of alogliptin and pioglitazone combination therapy on various aspects of beta-cell function in patients with recent-onset type 2 diabetes.
- 2014
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In: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 170:4, s. 565-574
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Journal article (peer-reviewed)abstract
- Type 2 diabetes (T2DM) management requires continuous treatment intensification due to progressive beta-cell function decline in insulin resistant individuals. Initial combination therapy of a dipeptidyl peptidase (DPP)-4 inhibitor with a thiazolidinedione (TZD) may be rational. We assessed the effects of the DPP-4 inhibitor alogliptin (ALO) combined with the TZD pioglitazone (PIO), versus ALO monotherapy or placebo (PBO), on beta-cell function and glycemic control in T2DM.
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| 3. |
- Scholtes, Rosalie A., et al.
(author)
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The effects of dapagliflozin on cardio-renal risk factors in patients with type 2 diabetes with or without renin-angiotensin system inhibitor treatment : a post hoc analysis
- 2020
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In: Diabetes, obesity and metabolism. - : John Wiley & Sons. - 1462-8902 .- 1463-1326. ; 22:4, s. 549-556
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Journal article (peer-reviewed)abstract
- Aims: Renin-angiotensin system inhibitors (RASi) are the most effective treatments for diabetic kidney disease but significant residual renal risk remains, possibly because of other mechanisms of kidney disease progression unrelated to RAS that may be present. Sodium-glucose co-transporter-2 inhibitors reduce albuminuria and may complement RASi by offering additional renal protection. This post hoc analysis investigated the effects of dapagliflozin on cardio-renal risk factors in patients with type 2 diabetes (T2D) with increased albuminuria treated with or without RASi at baseline. Materials and methods: We evaluated the effects of dapagliflozin 10 mg/day over 12–24 weeks across 13 placebo-controlled studies in patients with T2D with a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g at baseline. Patients were divided into two subgroups based on treatment with or without RASi at baseline. Results: Compared with patients with RASi at baseline (n = 957), patients without RASi (n = 302) were younger, had a shorter duration of diabetes (7 vs. 12 years), higher estimated glomerular filtration rate (eGFR) and lower UACR, serum uric acid (sUA), body weight and systolic blood pressure. Placebo-adjusted treatment effects of dapagliflozin on UACR, eGFR, glycated haemoglobin and haematocrit over 24 weeks were similar across groups. Mean reductions in body weight and sUA were more distinct in patients without RASi treatment at baseline. Conclusions: Treatment with dapagliflozin over 24 weeks provides similar clinically relevant improvements in metabolic and haemodynamic parameters, and similar reductions in UACR, in patients with T2D with elevated albuminuria treated with or without RASi at baseline. © 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
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| 4. |
- van Raalte, Daniël H, et al.
(author)
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Exenatide improves β-cell function up to 3 years of treatment in patients with type 2 diabetes: a randomised controlled trial.
- 2016
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In: European journal of endocrinology. - 1479-683X. ; 175:4, s. 345-52
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Journal article (peer-reviewed)abstract
- Glucagon-like peptide (GLP)-1 receptor agonist treatment improves β-cell function. In this study, we investigated whether the improvements are sustained during a 3-year treatment period.Sixty-nine metformin-treated type 2 diabetes patients were randomised to the GLP1 receptor agonist, exenatide (EXE) twice daily (BID) or to insulin glargine (GLAR). β-cell function parameters were derived using the Mari model from standardised breakfast and lunch meals that were administered before treatment, and after 1 and 3years of treatment. EXE was administered before breakfast.Fifty-nine (EXE: n=30; GLAR: n=29) and thirty-six (EXE: n=16; GLAR: n=20) patients completed the meal at 1- and 3-year treatment respectively. After 3years, groups had comparable glycaemic control (HbA1c: EXE 6.6±0.2% and GLAR 6.9±0.2%; P=0.216). Compared with GLAR, at 1 and 3years, EXE induced a stronger reduction in post-breakfast glucose concentrations (P<0.001), with lower C-peptide levels (P<0.001). Compared with GLAR, EXE increased insulin secretion at 8mmol/L glucose throughout the study period (P<0.01). Both treatments improved β-cell glucose sensitivity after 1-year treatment. However, only EXE treatment sustained this improvement for 3years. No consistent changes in other β-cell parameters including rate sensitivity and potentiation were observed.Compared with GLAR, EXE improved the parameters of β-cell function, especially insulin secretion at 8mmol/L glucose and β-cell glucose sensitivity, which was sustained during the 3-year treatment period.
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