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Long-term effects of sitagliptin in patients with type 2 diabetes mellitus and hypertension: results from the PROLOGUE study.

ABSTRACT: Background:The effects of sitagliptin in patients with type 2 diabetes mellitus and hypertension are unclear. Therefore, we evaluated the long-term effects of sitagliptin in those patients. Methods:In the PROLOGUE study, 365 patients were diagnosed as type 2 diabetes mellitus and hypertension, and 189 patients in the sitagliptin group, 176 patients in the conventional group. Fasting blood glucose (FBG), HbA1c, systolic pressure (SP), diastolic pressure (DP), serum urea nitrogen (BUN) and serum creatinine (SCR) were measured at the beginning of the study and after 12 and 24 months of treatment. Results:FBS and HbA1c levels were not significantly decreased after treatment [12 months: OR: -3.1, 95% CI (-11.3, 5.0); OR: 0.1, 95% CI (0.0, 0.3); 24 months: OR: -0.1, 95% CI (-9.1, 8.8); OR: 0.1, 95% CI (0.0, 0.3), respectively]. BP and DP levels were not significantly decreased after treatment (12 months: OR: 0.9, 95% CI (-2.8, 4.6); OR: 0.6, 95% CI (-2.0, 3.2); 24 months: OR: -0.5, 95% CI (-4.2, 3.1); OR: -1.6, 95% CI (-41, 0.9), respectively]. Furthermore, BUN and SCR levels were not significantly decreased after treatment (12 months: OR: 0.0, 95%CI (-1.2, 1.2); OR: 0.0, 95% CI (-0.1, 0.0); 24 months: OR: 0.4, 95% CI (-1.0, 1.8); OR: -80.8, 95% CI (-201.3, 39.8), respectively]. After adjusting for confounding factors, our results did not change. Conclusions:In our study, there was no evidence that treatment with sitagliptin can improve FBS, BP, DP, BUN or SCR in patients with type 2 diabetes mellitus and hypertension. Trial Registration:University Hospital Medical Information Network Clinical Trials Registry UMIN000004490.

SUBMITTER: Ye Z

PROVIDER: S-EPMC5762373 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Long-term effects of sitagliptin in patients with type 2 diabetes mellitus and hypertension: results from the PROLOGUE study.

Ye Ziliang Z Li Hui H Lu Haili H Su Qiang Q Li Lang L

Oncotarget 20171206 67

<h4>Background</h4>The effects of sitagliptin in patients with type 2 diabetes mellitus and hypertension are unclear. Therefore, we evaluated the long-term effects of sitagliptin in those patients.<h4>Methods</h4>In the PROLOGUE study, 365 patients were diagnosed as type 2 diabetes mellitus and hypertension, and 189 patients in the sitagliptin group, 176 patients in the conventional group. Fasting blood glucose (FBG), HbA1c, systolic pressure (SP), diastolic pressure (DP), serum urea nitrogen (B ...[more]

PMID: 29340105

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Project description:IntroductionA post-marketing surveillance (PMS) study was conducted to confirm the long-term risk-benefit profile of sitagliptin administered to Japanese patients with type 2 diabetes mellitus (T2DM) under real-world conditions.MethodsThis prospective, multicentre, open-label PMS collected data from 3326 patients receiving sitagliptin according to the approved indication during the case registration period (July 2010-June 2012; observation period, 3 years). Safety was assessed via collection of data on adverse drug reactions (ADRs), estimated glomerular filtration rate (eGFR) and cardiovascular events whereas efficacy was assessed via changes in glycated hemoglobin (HbA1c).ResultsIn 3265 patients evaluated for safety, 270 ADRs occurred in 207 (6.3%) patients overall. Metabolism and nutrition disorders were the most common class of ADRs, occurring in 58 patients overall (53 non-serious, 5 serious) with hypoglycaemia (17 patients, 0.52%) the most common ADR. In patients with eGFR > 90 mL/min/1.73 m2 at baseline (mean ± SD, 106.42 ± 18.11 mL/min/1.73 m2, n = 584), eGFR declined by 11.83 ± 17.53 mL/min/1.73 m2 (P < 0.0001; n = 360) over the observation period whereas eGFR appeared to be relatively maintained in patients with lower baseline eGFR levels. Cardiovascular events were infrequent [occurring in 4 of 84 (4.76%) patients at high cardiovascular risk] with no distinct features in this Japanese population and the cumulative incidence [8.42% (3.12-21.70) at 36 months; n = 32] was similar to that noted in previous studies involving sitagliptin. In patients evaluated for efficacy, the overall change in HbA1c from baseline to final evaluation was mean ± SD - 0.68 ± 1.34% (P < 0.0001, n = 2070). Reductions in HbA1c tended to be greater in younger patients and patients with higher body mass index (BMI) and HbA1c values at the start of administration.ConclusionLong-term sitagliptin administration in the routine clinical practice setting is associated with good efficacy, including as monotherapy, with no additional safety concerns.

Project description:BACKGROUND:Experimental studies have suggested that dipeptidyl peptidase-4 (DPP-4) inhibitors provide cardiovascular protective effects. We performed a randomized study to evaluate the effects of sitagliptin added on to the conventional therapy compared with conventional therapy alone (diet, exercise, and/or drugs, except for incretin-related agents) on the intima-media thickness (IMT) of the carotid artery, a surrogate marker for the evaluation of atherosclerotic cardiovascular disease, in people with type 2 diabetes mellitus (T2DM). METHODS AND FINDINGS:We used a multicenter PROBE (prospective, randomized, open label, blinded endpoint) design. Individuals aged ?30 y with T2DM (6.2% ? HbA1c < 9.4%) were randomly allocated to receive either sitagliptin (25 to 100 mg/d) or conventional therapy. Carotid ultrasound was performed at participating medical centers, and all parameters were measured in a core laboratory. Of the 463 enrolled participants with T2DM, 442 were included in the primary analysis (sitagliptin group, 222; conventional therapy group, 220). Estimated mean (± standard error) common carotid artery IMT at 24 mo of follow-up in the sitagliptin and conventional therapy groups was 0.827 ± 0.007 mm and 0.837 ± 0.007 mm, respectively, with a mean difference of -0.009 mm (97.2% CI -0.028 to 0.011, p = 0.309). HbA1c level at 24 mo was significantly lower with sitagliptin than with conventional therapy (6.56% ± 0.05% versus 6.72% ± 0.05%, p = 0.008; group mean difference -0.159, 95% CI -0.278 to -0.041). Episodes of serious hypoglycemia were recorded only in the conventional therapy group, and the rate of other adverse events was not different between the two groups. As it was not a placebo-controlled trial and carotid IMT was measured as a surrogate marker of atherosclerosis, there were some limitations of interpretation. CONCLUSIONS:In the PROLOGUE study, there was no evidence that treatment with sitagliptin had an additional effect on the progression of carotid IMT in participants with T2DM beyond that achieved with conventional treatment. TRIAL REGISTRATION:University Hospital Medical Information Network Clinical Trials Registry UMIN000004490.

Project description:BackgroundMiscarriages affect up to a fifth of all pregnancies and are associated with substantial psychological morbidity. However, their relationship with cardiometabolic risk factors is not well known. Therefore, in this study we aimed to estimate the burden of cardiovascular risk factors including diabetes mellitus (type 1 or 2) and hypertension in women with miscarriage compared to women without a record of miscarriage.MethodsA population-based retrospective cohort study was conducted using IVQIA Medical Research Data UK (IMRD-UK) between January 1995 and May 2016, an anonymised electronic health records database that is representative of the UK population. A total of 86,509, 16-50-year-old women with a record of miscarriage (exposed group) were matched by age, smoking status, and body mass index to 329,865 women without a record of miscarriage (unexposed group). Patients with pre-existing hypertension and diabetes were excluded. Adjusted incidence rate ratios (aIRR) and 95% confidence intervals (95% CI) for diabetes and hypertension were estimated using multivariable Poisson regression models offsetting for person-years follow-up.ResultsThe mean age at cohort entry was 31 years and median follow up was 4.6 (IQR 1.7-9.4) years. During the study period, a total of 792 (IR 1.44 per 1000 years) and 2525 (IR 1.26 per 1000 years) patients developed diabetes in the exposed and unexposed groups, respectively. For hypertension, 1995 (IR 3.73 per 1000 years) and 1605 (IR 3.39 per 1000 years) new diagnoses were recorded in the exposed and unexposed groups, respectively. Compared to unexposed individuals, women with a record miscarriage were more likely to develop diabetes (aIRR = 1.25, 95% CI: 1.15-1.36; p<0.001) and hypertension (aIRR = 1.07, 95% CI: 1.02-1.12; p = 0.005).ConclusionsWomen diagnosed with miscarriage were at increased risk of developing diabetes mellitus and hypertension. Women with history of miscarriage may benefit from periodic monitoring of their cardiometabolic health.

Project description:UnlabelledGPR119 receptor agonists improve glucose metabolism and alter gut hormone profiles in animal models and healthy subjects. We therefore investigated the pharmacology of GSK1292263 (GSK263), a selective GPR119 agonist, in two randomized, placebo-controlled studies that enrolled subjects with type 2 diabetes. Study 1 had drug-naive subjects or subjects who had stopped their diabetic medications, and Study 2 had subjects taking metformin. GSK263 was administered as single (25-800 mg; n = 45) or multiple doses (100-600 mg/day for 14 days; n = 96). Placebo and sitagliptin 100 mg/day were administered as comparators. In Study 1, sitagliptin was co-administered with GSK263 or placebo on Day 14 of dosing. Oral glucose and meal challenges were used to assess the effects on plasma glucose, insulin, C-peptide, glucagon, peptide tyrosine-tyrosine (PYY), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). After 13 days of dosing, GSK263 significantly increased plasma total PYY levels by ∼ five-fold compared with placebo, reaching peak concentrations of ∼ 50 pM after each of the three standardized meals with the 300 mg BID dose. Co-dosing of GSK263 and metformin augmented peak concentrations to ∼ 100 pM at lunchtime. GSK263 had no effect on active or total GLP-1 or GIP, but co-dosing with metformin increased post-prandial total GLP-1, with little effect on active GLP-1. Sitagliptin increased active GLP-1, but caused a profound suppression of total PYY, GLP-1, and GIP when dosed alone or with GSK263. This suppression of peptides was reduced when sitagliptin was co-dosed with metformin. GSK263 had no significant effect on circulating glucose, insulin, C-peptide or glucagon levels. We conclude that GSK263 did not improve glucose control in type 2 diabetics, but it had profound effects on circulating PYY. The gut hormone effects of this GPR119 agonist were modulated when co-dosed with metformin and sitagliptin. Metformin may modulate negative feedback loops controlling the secretion of enteroendocrine peptides.Trial registrationClinicaltrials.gov NCT01119846 Clinicaltrials.gov NCT01128621.

Dataset Information

Long-term effects of sitagliptin in patients with type 2 diabetes mellitus and hypertension: results from the PROLOGUE study.

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Long-term effects of sitagliptin in patients with type 2 diabetes mellitus and hypertension: results from the PROLOGUE study.

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