S-EPMC10980368 - Effects of high-intensity statin combined with telmisartan versus amlodipine on glucose metabolism in hypertensive atherosclerotic cardiovascular disease patients with impaired fasting glucose: A randomized multicenter trial. - OmicsDI

Unknown

Dataset Information

Effects of high-intensity statin combined with telmisartan versus amlodipine on glucose metabolism in hypertensive atherosclerotic cardiovascular disease patients with impaired fasting glucose: A randomized multicenter trial.

ABSTRACT:

Background

There is lacking evidence that telmisartan can improve insulin resistance in patients on high-intensity statins. This study compared the effects of telmisartan and amlodipine on glucose metabolism in hypertensive atherosclerotic cardiovascular disease (ASCVD) patients with impaired fasting glucose (IFG) requiring high-intensity rosuvastatin therapy.

Methods

Ninety-nine patients were randomly assigned to 2 groups [telmisartan-statin group (n=48) and amlodipine-statin group (n=51)] as add-on therapy to high-intensity rosuvastatin therapy (20 mg). The primary endpoint was to assess insulin resistance using the homeostatic model assessment (HOMA-IR) value at week 24. The secondary endpoint was the change in glucose metabolism indices from baseline to week 24.

Results

The HOMA-IR at week 24 (2.4 [interquartile range, 1.8-3.8] versus 2.7 [1.7-3.7]; P = .809) and changes in the HOMA-IR from baseline to week 24 (-7.0 [-29.0 to 21.0] versus -5.5 [-53.3 to 27.3]; P = .539) were not significantly different between 2 groups. However, the fasting glucose level at week 24 was significantly lower in the telmisartan-statin group than in the amlodipine-statin group (107.7 ± 13.4 mg/dL versus 113.3 ± 12.4 mg/dL; P = .039) and significantly decreased in the telmisartan-statin group (-3.2 ± 8.6% versus 3.8 ± 13.2%; P = .003). The proportion of patients with fasting glucose ≥100 mg/dL (71.1% versus 89.6%; P = .047) or new-onset diabetes mellitus (12.5% versus 31.4%, P = .044) at week 24 was also significantly lower in the telmisartan-statin group than in the amlodipine-statin group.

Conclusion

In comparison to amlodipine, telmisartan did not decrease the HOMA-IR. However, telmisartan preserved insulin secretion, led to a regression from IFG to euglycemia and prevented new-onset diabetes mellitus in ASCVD patients with IFG requiring high-intensity statins.

SUBMITTER: Lee CJ

PROVIDER: S-EPMC10980368 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

Effects of high-intensity statin combined with telmisartan versus amlodipine on glucose metabolism in hypertensive atherosclerotic cardiovascular disease patients with impaired fasting glucose: A randomized multicenter trial.

Lee Chan Joo CJ Sung Jung-Hoon JH Kang Tae-Soo TS Park Sungha S Lee Sang-Hak SH Kim Jong-Youn JY Kim Byeong-Kuek BK

Medicine 20220901 36

<h4>Background</h4>There is lacking evidence that telmisartan can improve insulin resistance in patients on high-intensity statins. This study compared the effects of telmisartan and amlodipine on glucose metabolism in hypertensive atherosclerotic cardiovascular disease (ASCVD) patients with impaired fasting glucose (IFG) requiring high-intensity rosuvastatin therapy.<h4>Methods</h4>Ninety-nine patients were randomly assigned to 2 groups [telmisartan-statin group (n=48) and amlodipine-statin gro ...[more]

Similar Datasets

Project description:BackgroundThe efficacy of a combination of a calcium channel blocker (CCB) plus chlorthalidone (diuretic) versus a CCB plus an angiotensin receptor blocker (ARB) in patients not responding to CCB monotherapy has not been evaluated previously. We plan to compare the efficacy and safety of S-amlodipine (CCB) plus chlorthalidone versus S-amlodipine plus telmisartan (ARB) combinations among hypertension patients unresponsive to amlodipine monotherapy.Methods/designThis study is a prospective, randomized, double-blind, multicenter, parallel, non-inferiority phase 4 study. Hypertension patients who have been treated with amlodipine (5 mg) or S-amlodipine (2.5 mg) monotherapy for ≥2 weeks and whose mean diastolic blood pressure (DBP) is greater than 90 mmHg will be randomized to either S-amlodipine (2.5 mg) plus chlorthalidone (25 mg) or S-amlodipine (2.5 mg) plus telmisartan (40 mg) therapy. The primary efficacy endpoint is mean sitting DBP change after 12 weeks of treatment. The study objective is to prove the non-inferiority of the former combination (test drug) as compared to the latter one (control) with a non-inferiority margin of 3 mmHg in mean DBP change. The secondary endpoints are 6-week DBP change, 6- and 12-week sitting systolic BP (SBP) change, and the attainment of the target BP (SBP < 140 mmHg or DBP < 90 mmHg). Urine albumin, albumin/creatinine ratio (ACR), pulse wave velocity, central BP, 24-h ambulatory BP monitoring, and body fluid composition analysis will be performed at each hospital's discretion. The sample size was estimated as 170 in total with 1:1 randomization.DiscussionThis is the first study comparing the efficacy of a CCB plus chlorthalidone versus a CCB plus an ARB in patients who are not responding to CCB single therapy. The study result will help clinicians to choose between chlorthalidone and telmisartan in CCB-unresponsive patients.Trial registrationClinicalTrials.gov , NCT03226340. Registered on 2 December 2015.

Project description:BackgroundAround 308 million people worldwide are estimated to have impaired glucose tolerance (IGT); 25% to 75% of these will develop diabetes within a decade of initial diagnosis. At diagnosis, half will have tissue-related damage and all have an increased risk for coronary heart disease.ObjectivesThe objective of this review was to assess the effects and safety of Chinese herbal medicines for the treatment of people with impaired glucose tolerance or impaired fasting glucose (IFG).Search strategyWe searched the following databases: The Cochrane Library, PubMed, EMBASE, AMED, a range of Chinese language databases, SIGLE and databases of ongoing trials.Selection criteriaRandomised clinical trials comparing Chinese herbal medicines with placebo, no treatment, pharmacological or non-pharmacological interventions in people with IGT or IFG were considered.Data collection and analysisTwo authors independently extracted data. Trials were assessed for risk of bias against key criteria: random sequence generation, allocation concealment, blinding of participants, outcome assessors and intervention providers, incomplete outcome data, selective outcome reporting and other sources of bias.Main resultsThis review examined 16 trials lasting four weeks to two years involving 1391 participants receiving 15 different Chinese herbal medicines in eight different comparisons. No trial reported on mortality, morbidity or costs. No serious adverse events like severe hypoglycaemia were observed. Meta-analysis of eight trials showed that those receiving Chinese herbal medicines combined with lifestyle modification were more than twice as likely to have their fasting plasma glucose levels return to normal levels (i.e. fasting plasma glucose <7.8 mmol/L and 2hr blood glucose <11.1 mmol/L) compared to lifestyle modification alone (RR 2.07; 95% confidence intervall (CI) 1.52 to 2.82). Those receiving Chinese herbs were less likely to progress to diabetes over the duration of the trial (RR 0.33; 95% CI 0.19 to 0.58). However, all trials had a considerable risk of bias and none of the specific herbal medicines comparison data was available from more than one study. Moreover, results could have been confounded by rates of natural reversion to normal glucose levels.Authors' conclusionsThe positive evidence in favour of Chinese herbal medicines for the treatment of IGT or IFG is constrained by the following factors: lack of trials that tested the same herbal medicine, lack of details on co-interventions, unclear methods of randomisation, poor reporting and other risks of bias.

Project description:ObjectiveThis study examined the prevalence of impaired fasting glucose (IFG) and diabetes and their associated factors in 17,184 Chinese hypertensive adults aged 45-75 years.MethodsA cross-sectional investigation was carried out in a rural area of Lianyungang, China. Previously undiagnosed diabetes [fasting plasma glucose (FPG) ≥ 7.0 mmol/l] and IFG (6.1-6.9 mmol/l) were defined based on FPG concentration. Previously diagnosed diabetes was determined on the basis of self-report. Total diabetes included both previously diagnosed diabetes and previously undiagnosed diabetes.ResultsThe prevalence of previously diagnosed diabetes, undiagnosed diabetes, and IFG were 3.4%, 9.8%, and 14.1%, respectively. About 74.2% of the participants with diabetes had not previously been diagnosed. In the multivariable logistic-regression model, older age, men, antihypertensive treatment, obesity (BMI ≥ 25 kg/m(2)), abdominal obesity (waist circumference ≥ 90 cm for men and ≥ 80 cm for women), non-current smoking, a family history of diabetes, higher heart rate, lower physical activity levels, and inland residence (versus coastal) were significantly associated with both total diabetes and previously undiagnosed diabetes. Furthermore, methylene- tetrahydrofolate reductase (MTHFR) 677 TT genotype was an independent associated factor for total diabetes, and current alcohol drinking was an independent associated factor for previously undiagnosed diabetes. At the same time, older age, men, abdominal obesity, non-current smoking, current alcohol drinking, a family history of diabetes, higher heart rate, and inland residence (versus coastal) were important independent associated factors for IFG.ConclusionIn conclusion, we found a high prevalence of diabetes in Chinese hypertensive adults. Furthermore, about three out of every four diabetic adults were undiagnosed. Our results suggest that population-level measures aimed at the prevention, identification (even if only based on the FPG evaluation), and treatment of diabetes should be urgently taken to overcome the diabetes epidemic in Chinese hypertensive adults.

Project description:BackgroundRemnant cholesterol (RC), a potent atherogenic lipid, has been shown to be strongly correlated with insulin resistance and the pathogenesis of diabetes mellitus. However, the relationship between RC and normoglycemia reversal in individuals with impaired fasting glucose (IFG) is crucial and remains unclear. This investigation, which aimed to clarify this association, is important for understanding and potentially improving the management of diabetes.MethodThis study, which included 15,019 IFG participants from 11 Chinese cities between 2010 and 2016, was conducted with a rigorous research process. Cox regression analysis revealed intriguing findings regarding the relationship between RC and normoglycemia reversal in individuals with IFG. Potential nonlinear associations were further explored via smooth curve-fitting techniques and 4-knot restricted cubic spline functions, ensuring a comprehensive analysis. To examine the validity of the results, an array of subgroup and sensitivity analyses were conducted, further bolstering the robustness of the findings.ResultsBy the end of the 2.89-year median follow-up period, 6,483 of the 15,019 IFG participants (43.17%) had reverted to normoglycemia. The findings, which reveal that increased RC levels are inversely associated with the likelihood of normoglycemia reversal, are novel and significant. According to the fully adjusted Cox proportional hazards model analysis, an increase of one standard deviation in RC was associated with a 20% decrease in the likelihood of normoglycemia reversal among IFG participants (HR: 0.80, 95% CI: 0.77-0.82). A nonlinear association between RC and normoglycemia reversal was observed, with an inflection point at 41.37 mg/dL. This suggests that the growth rate of the likelihood of reversion decreased and stabilized after the inflection point was reached. Moreover, significant interactions were observed between the age groups, providing a more nuanced understanding of this complex relationship.ConclusionAmong Chinese adults with IFG, RC exhibited a negative nonlinear relationship with the probability of normoglycemia reversal. When RC levels reached or exceeded 41.38 mg/dL, the probability of achieving normoglycemia progressively diminished and subsequently stabilized. Maintaining RC levels below 41.38 mg/dL can significantly improve the probability of normoglycemia reversal among individuals with IFG, especially those aged 60 years or older.

Project description:PurposeA new fixed-dose combination (FDC) formulation of telmisartan 80 mg and S-amlodipine 5 mg (CKD-828) has been developed to increase convenience (as only one tablet is required per day) and improve treatment compliance.MethodsThe pharmacokinetic characteristics and tolerability of an FDC of telmisartan and S-amlodipine were compared to those after coadministration of the individual agents in this randomized, open-label, single-dose, two-way, four-period, crossover study. To analyze the telmisartan and S-amlodipine plasma concentrations using a validated liquid chromatography-tandem mass spectrometry method, serial blood samples were collected up to 48 hours post-dose for telmisartan and 144 hours post-dose for S-amlodipine, in each period.ResultsForty-eight healthy subjects were enrolled, and 43 completed the study. The mean peak plasma concentration (Cmax) and the area under the plasma concentration-time curve from time 0 to the last measurement (AUC0-t) values of telmisartan were 522.29 ng/mL and 2,475.16 ng·h/mL for the FDC, and 540.45 ng/mL and 2,559.57 ng·h/mL for the individual agents concomitantly administered, respectively. The mean Cmax and AUC0-t values of S-amlodipine were 2.71 ng/mL and 130.69 ng·h/mL for the FDC, and 2.74 ng/mL and 129.81 ng·h/mL for the individual agents concomitantly administered, respectively. The geometric mean ratio (GMR) and 90% confidence interval (CI) for the telmisartan Cmax and AUC0-t (FDC of telmisartan and S-amlodipine/concomitant administration) were 0.8509 (0.7353-0.9846) and 0.9431 (0.8698-1.0226), respectively. The GMR and 90% CI for the S-amlodipine Cmax and AUC0-t (FDC/concomitant administration) were 0.9829 (0.9143-1.0567) and 0.9632 (0.8798-1.0546), respectively. As the intrasubject variability of the Cmax for telmisartan administered individually was 42.94%, all 90% CIs of the GMRs fell within the predetermined acceptance range. Both treatments were well tolerated in this study.ConclusionCKD-828 FDC tablets were shown to be bioequivalent to coadministration of the individual agents with the respective strength, in healthy subjects under fasting conditions. There was no significant difference in safety profile between the two treatments.