Benefits and Risks of Aliskiren Treatment in Patients With Type 2 Diabetes: Analyses of the 3A Registry.
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ABSTRACT:
SUBMITTER: Kistner I
PROVIDER: S-EPMC8031948 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Sodium-glucose co-transporter 2 (SGLT2) inhibitors, such as canagliflozin, are used in patients with Type 2 diabetes mellitus (T2DM). In clinical studies, canagliflozin significantly reduced A1C, bodyweight and blood pressure, and was generally well tolerated with no increased risk of hypoglycemia. Most common adverse effects observed were genital mycotic infections and urinary tract infections, and increased urination. Approximately 10% of women treated with canagliflozin experienced a genital mycotic infection compared with 3% treated with placebo; those with a prior history were at greater risk. Approximately 9% of women treated with canagliflozin reported a urinary tract infection compared with 7% treated with placebo. Most adverse events were considered mild to moderate in intensity and responded to standard therapy. Treatment with canagliflozin was effective and generally well tolerated in both women (and men) with T2DM.
| S-EPMC5384506 | biostudies-literature
Project description:Sodium-glucose co-transporter-2 (SGLT2) inhibitors have several beneficial effects in patients with type 2 diabetes, including glucose lowering, weight loss, blood pressure lowering, and a reduced risk of major adverse cardiovascular events. To address high unmet medical need via improved glycaemic control, several clinical trials have been done to assess the efficacy and safety of SGLT2 inhibitors in combination with insulin therapy in patients with type 1 diabetes. In this Personal View, we summarise data from eight clinical trials of canagliflozin, dapagliflozin, empagliflozin, and sotagliflozin in patients with type 1 diabetes. HbA1c-lowering efficacy was greatest at 8-12 weeks of therapy, but the magnitude of HbA1c lowering waned with longer duration of treatment (up to 52 weeks). Data are not yet available to establish for how long glycaemic efficacy could be sustained during long-term therapy in patients with type 1 diabetes. Moreover, SGLT2 inhibitor therapy induces serious adverse events, including a roughly six-times increased risk of diabetic ketoacidosis. The US Food and Drug Administration estimated that one additional case of ketoacidosis will occur for every 26 patient-years of exposure of patients with type 1 diabetes to sotagliflozin therapy. Assuming a case mortality of 0·4%, this estimate translates into 16 additional deaths per year per 100 000 patients with type 1 diabetes undergoing treatment. These considerations raise important questions about the risk-to-benefit profile of SGLT2 inhibitors when used as adjunctive therapy in patients with type 1 diabetes.
| S-EPMC6872914 | biostudies-literature
Project description:The safety and usefulness of pioglitazone (Pio) is repeatedly called into question due to the contradictory information available about it. A meta-analysis and risk benefit assessment was conducted to address the various points of debate regarding Pio. Electronic database search (Cochrane library, Embase & PubMed) resulted in 10 citations eligible for this meta-analysis (prospective, randomised studies), which was conducted using CMA software version 3 (Biostat Inc., Englewood, NJ, USA). The meta-analysis was registered with PROSPERO (ID: CRD42019122403) and compared pioglitazone with a control (anti-hyperglycemic agents without pioglitazone) in patients with either established cardiovascular disease or having high cardiovascular risk. Sensitivity and subgroup analysis were conducted to differentiate the effect of Pio against active controls and placebo. The use of Pio compared to the control group that did not use Pio resulted in a 14% and 23% significant reduction in odds of major adverse cardiac events (MACE: MH-OR, 0.86; 95% CI 0.75-0.98), and stroke (MH-OR, 0.77; 95% CI 0.60-0.99), respectively. This reduction in stroke was not significant in comparison to placebo on subgroup analysis. However, Pio significantly increased odds of heart failure (HF) (MH-OR, 1.47; 95% CI 1.26-1.71) as well as hospitalization for heart failure (hHF) (MH-OR, 1.48; 95% CI 1.21-1.81). In addition, the use of Pio was associated with a significant increase in odds of fractures in women (MH-OR, 2.05; 95% CI 1.28-3.27) and anaemia (MH-OR, 2.56; 95% CI 1.55-4.21). Pio has no significant effect on bladder cancer nor macular oedema. Pio has salutary effects on MACE. The positive effects are completely offset by the harm they seem to cause by way of heart failure, fractures, and anaemia. Pio should therefore be reserved for treatment of T2D with high CV risk or established cardiovascular (CV) disease only in selected patients where other antidiabetics are precluded and not routinely.
| S-EPMC7519682 | biostudies-literature
Project description:IntroductionRenin-angiotensin system inhibitors have been reported to exert protective effects against organ damage and failure; however, the impact of direct renin inhibitor as monotherapy has not been assessed. Here we investigated the effects of 24-week monotherapy with aliskiren compared to amlodipine in hypertensive patients with type 2 diabetes or obesity.MethodsIn this randomized intervention study, 62 adult hypertensive patients with visceral obesity (defined as a body mass index [BMI] greater than 25 kg/m2 and visceral adipose tissue area [VFA] greater than 100 cm2) or type 2 diabetes mellitus (age 57 ± 13, 65% men, BMI 28.8 ± 4.8 kg/m2, VFA 134.8 ± 47.0 cm2, blood pressure 141 ± 16/86 ± 13 mmHg) were randomized to receive 24-week treatment with aliskiren (max. 300 mg) or amlodipine (max. 10 mg). The primary outcome was the change in VFA at 24 weeks post-treatment.ResultsChange in VFA did not differ significantly from baseline in either group. Systolic blood pressure significantly decreased at 12 weeks (-10 mmHg, P = 0.001) and 24 weeks (-10 mmHg, P = 0.001) in the amlodipine group and at 24 weeks (-11 mmHg, P = 0.001) in the aliskiren group. Diastolic blood pressure significantly decreased at 24 weeks (-6 mmHg, P = 0.009) only in the amlodipine group. Although the estimated glomerular filtration rates did not significantly change in either group, the logarithm of urinary albumin excretion significantly decreased at 24 weeks only in the aliskiren group (-0.60, P < 0.001). The 24-week changes in the urinary albumin excretion significantly correlated with the changes in the plasma renin activity in the aliskiren group (r = 0.51, P = 0.008).ConclusionAliskiren monotherapy did not show any superiority to amlodipine monotherapy on VFA, estimated glomerular filtration rates, or urinary albumin excretion in obese or type 2 diabetic hypertensive patients.
| S-EPMC10652658 | biostudies-literature
Project description:The Aliskiren in the Evaluation of Proteinuria in Diabetes (AVOID) trial demonstrated that adding aliskiren, an oral direct renin inhibitor, at a dosage of 300 mg/d to the highest approved dosage of losartan and optimal antihypertensive therapy reduces albuminuria over 6 mo among patients with type 2 diabetes, hypertension, and albuminuria. The cost-effectiveness of this therapy, however, is unknown. Here, we used a Markov model to project progression to ESRD, life years, quality-adjusted life years, and lifetime costs for aliskiren plus losartan versus losartan. We used data from the AVOID study and the Irbesartan in Diabetic Nephropathy Trial (IDNT) to estimate probabilities of progression of renal disease. We estimated probabilities of mortality for ESRD and other comorbidities using data from the US Renal Data System, US Vital Statistics, and published studies. We based pharmacy costs on wholesale acquisition costs and based costs of ESRD and transplantation on data from the US Renal Data System. We found that adding aliskiren to losartan increased time free of ESRD, life expectancy, and quality-adjusted life expectancy by 0.1772, 0.1021, and 0.0967 yr, respectively. Total expected lifetime health care costs increased by $2952, reflecting the higher pharmacy costs of aliskiren and losartan ($7769), which were partially offset by savings in costs of ESRD ($4860). We estimated the cost-effectiveness of aliskiren to be $30,500 per quality-adjusted life year gained. In conclusion, adding aliskiren to losartan and optimal therapy in patients with type 2 diabetes, hypertension, and albuminuria may be cost-effective from a US health care system perspective.
| S-EPMC2754109 | biostudies-other
Project description:PURPOSE:Cancer patients are increasingly involved in decision-making processes. Hence, clinicians need to inform patients about the risks and benefits of different treatment options in order for patients to make well informed decisions. The aim of this review is to determine the effects of methods of communicating prognostic information about (1) disease progression (survival, progression, recurrence and remission), (2) side effects and complications and (3) health-related quality of life (HRQL) on cognitive, affective and behavioral outcomes in cancer patients. METHODS:A literature search was performed to select articles that were published up to November 2019 and that examined verbal and/or visual risk communication interventions in an oncological clinical setting. RESULTS:The search yielded 14,875 studies; 28 studies were ultimately included. For disease progression information, we found that framing affects treatment choice. Furthermore, limiting the amount of progression information in a graphical display could benefit patients' understanding of risks and benefits. For prognostic information about side effects and complications, precise and defined risk information was better understood than information presented in words. When displaying HRQL data, no consensus was found on which graph type to use. CONCLUSION:Great heterogeneity in the results and methodology and in the compared communication formats precluded us from drawing any further conclusions. Practical implications for clinicians are to consider the effects that different types of framing might have on the patient and to not rely exclusively on words to describe risks, but rather include at least some form of numbers or visualization.
| S-EPMC7295838 | biostudies-literature
Project description:Objective:Precision medicine drug therapy seeks to maximize efficacy and minimize harm for individual patients. This will be difficult if drug response and side effects are positively associated, meaning that patients likely to respond best are at increased risk of side effects. We applied joint longitudinal-survival models to evaluate associations between drug response (longitudinal outcome) and the risk of side effects (survival outcome) for patients initiating type 2 diabetes therapy. Study design and setting:Participants were randomized to metformin (MFN), sulfonylurea (SU), or thiazolidinedione (TZD) therapy in the A Diabetes Outcome Progression Trial (ADOPT) drug efficacy trial (n=4,351). Joint models were parameterized for 1) current HbA1c response (change from baseline in HbA1c) and 2) cumulative HbA1c response (total HbA1c change). Results:With MFN, greater HbA1c response did not increase the risk of gastrointestinal events (HR per 1% absolute greater current response 0.82 [95% CI 0.67, 1.01]; HR per 1% higher cumulative response 0.90 [95% CI 0.81, 1.00]). With SU, greater current response was associated with an increased risk of hypoglycemia (HR 1.41 [95% CI 1.04, 1.91]). With TZD, greater response was associated with an increased risk of edema (current HR 1.45 [95% CI 1.05, 2.01]; cumulative 1.22 [95% CI 1.07, 1.38]) but not fracture. Conclusion:Joint modeling provides a useful framework to evaluate the association between response to a drug and the risk of developing side effects. There may be great potential for widespread application of joint modeling to evaluate the risks and benefits of both new and established medications.
| S-EPMC6298877 | biostudies-other
Project description:BackgroundCurrent guidelines recommend withholding antithrombotic therapy (ATT) for at least 24 h in patients with acute ischemic stroke treated with thrombolytic therapy. Herein, we report a retrospective analysis of a single-centre experience on the safety and efficacy of antithrombotic therapy (ATT) started before or after 24 h of intravenous thrombolysis in a cohort of acute ischemic stroke patients.MethodsA total of 139 patients (Rapid ATT group) received antithrombotic therapy before 24 h of thrombolysis, and 33 patients (Standard ATT group) after 24 h. The brain parenchyma and vessel status were assessed using simple CT scan on admission, multimodal CT scan at the end of thrombolysis, and angio-CT/MRI scan at day 3. Functional outcome was scored using the modified Rankin Scale (mRS) at day 90.ResultsThe two ATT groups had similar demographics, stroke subtypes, baseline NIHSS, thrombolytic strategies, vessel-patency rates at the end of thrombolysis, and incidence of bleeding complications at follow up. At day 3, the Rapid ATT group had a non-significant improved vessel-patency rate than the Standard ATT group. At day 90, a greater proportion of patients in the rapid ATT group had shifted down the mRS, and had improved in the NIHSS score.ConclusionsATT initiated before 24 h of intravenous thrombolytic therapy in acute stroke patients disclosed no safety concerns compared with a conventional antithrombotic therapy delay of 24 h and showed better functional outcome at follow up. The value of early initiation of ATT after thrombolysis deserves further assessment in randomized controlled trials.
| S-EPMC3738638 | biostudies-literature
Project description:We investigated whether atorvastatin 10 mg daily lowered C-reactive protein (CRP) and whether the effects of atorvastatin on cardiovascular disease (CVD) varied by achieved levels of CRP and LDL-cholesterol.CRP levels were measured at baseline and 1 year after randomisation to atorvastatin in 2,322 patients with type 2 diabetes (40-75 years, 69% males) in a secondary analysis of the Collaborative Atorvastatin Diabetes Study, a randomised placebo-controlled trial. We used Cox regression models to test the effects on subsequent CVD events (n = 147) of CRP and LDL-cholesterol lowering at 1 year.After 1 year, the atorvastatin arm showed a net CRP lowering of 32% (95% CI -40%, -22%) compared with placebo. The CRP response was highly variable, with 45% of those on atorvastatin having no decrease in CRP (median [interquartile range, IQR] per cent change -9.8% [-57%, 115%]). The LDL-cholesterol response was less variable, with a median (IQR) within-person per cent change of -41% (-51%, -31%). Baseline CRP did not predict CVD over 3.8 years of follow-up (HRper SD log 0.89 [95% CI 0.75, 1.06]), whereas baseline LDL-cholesterol predicted CVD (HRper SD 1.21 [95% CI 1.02, 1.44]), as did on-treatment LDL-cholesterol. There was no significant difference in the reduction in CVD by atorvastatin, with above median (HR 0.57) or below median (HR 0.52) change in CRP or change in LDL-cholesterol (HR 0.61 vs 0.50).CRP was not a strong predictor of CVD. Statin efficacy did not vary with achieved CRP despite considerable variability in CRP response. The use of CRP as an indicator of efficacy of statin therapy on CVD risk in patients with type 2 diabetes is not supported by these data. Trial registration NCT00327418.
| S-EPMC4472939 | biostudies-literature
Project description:We investigated whether the antiproteinuric effect of the direct renin inhibitor aliskiren is comparable to that of irbesartan and the effect of the combination.This was a double-blind, randomized, crossover trial. After a 1-month washout period, 26 patients with type 2 diabetes, hypertension, and albuminuria (>100 mg/day) were randomly assigned to four 2-month treatment periods in random order with placebo, 300 mg aliskiren once daily, 300 mg irbesartan once daily, or the combination using identical doses. Patients received furosemide in a stable dose throughout the study. The primary end point was a change in albuminuria. Secondary measures included change in 24-h blood pressure and glomerular filtration rate (GFR).Placebo geometric mean albuminuria was 258 mg/day (range 84-2,361), mean +/- SD 24-h blood pressure was 140/73 +/- 15/8 mmHg, and GFR was 89 +/- 27 ml/min per 1.73 m(2). Aliskiren treatment reduced albuminuria by 48% (95% CI 27-62) compared with placebo (P < 0.001), not significantly different from the 58% (42-79) reduction with irbesartan treatment (P < 0.001 vs. placebo). Combination treatment reduced albuminuria by 71% (59-79), more than either monotherapy (P < 0.001 and P = 0.028). Fractional clearances of albumin were significantly reduced (46, 56, and 67% reduction vs. placebo). Twenty-four-hour blood pressure was reduced 3/4 mmHg by aliskiren (NS/P = 0.009), 12/5 mmHg by irbesartan (P < 0.001/P = 0.002), and 10/6 mmHg by the combination (P = 0.001/P < 0.001). GFR was significantly reduced 4.6 (95% CI 0.3-8.8) ml/min per 1.73 m(2) by aliskiren, 8.0 (3.6-12.3) ml/min per 1.73 m(2) by irbesartan, and 11.7 (7.4-15.9) ml/min per 1.73 m(2) by the combination.The combination of aliskiren and irbesartan is more antiproteinuric in type 2 diabetic patients with albuminuria than monotherapy.
| S-EPMC2752919 | biostudies-literature