The changing therapeutic armamentarium for patients with type 1 diabetes.

PURPOSE OF REVIEW: This article evaluates the role of Sodium glucose co-transporter-2 (SGLT-2) inhibitor and Glucagon-like peptide-1 receptor agonist's (GLP-1 RA's)s in the treatment of type 1 diabetes (T1D). RECENT FINDINGS: Both agents help to produce a small reduction in HbA1C levels with accompanying weight loss. Submaximal doses of SGLT-2 inhibitors may reduce the risk for hypoglycemia as well as limit glycemic variability. However, SGLT-2 inhibitors appear to increase rates of ketone body production and diabetic ketoacidosis, and therefore must only be used in the setting of appropriate risk mitigation. GLP-1 RA's increased the risk for hypoglycemia in the largest clinical trial done to date (with a small fall in A1C), which lead to a cessation of the development of liraglutide as a treatment for T1D. SUMMARY: Off-label use of medications designed for individuals with type 2 diabetes in people with T1D has potential benefits as well as risks. If using an SGLT-2 inhibitor or a GLP-1 RA, it is important to have an informed, educated patient and follow a specific protocol. In the case of SGLT-2 inhibitors, clinical trials should help define how to use these agents more safely and effectively in T1D.

Meta-analysis of Ivabradine in Patients With Stable Coronary Artery Disease With and Without Left Ventricular Dysfunction.

PURPOSE: Ivabradine is a novel If-channel antagonist that controls heart rate and may be helpful in treating patients with left ventricular dysfunction (LVD) who are unable to tolerate ß-blockers or achieve a heart rate of 70 beats/min with standard therapy. Three landmark trials were used for the approval of ivabradine in the United States. These trials tested ivabradine in addition to a standard of care (including ß-blockers) in patients with stable coronary artery disease (CAD) and found modest benefit in those with established LVD unable to tolerate ß-blockers. The goal of this review was to pool data from ivabradine studies in all patients with stable CAD to compare cardiovascular and safety-related outcomes. METHODS: Three randomized, double-blind, placebo-controlled trials of ivabradine added to standard treatment (including ß-blockers) in patients with stable CAD with and without LVD were reviewed for effects on mortality, cardiovascular outcomes, and adverse events. Data were independently abstracted by 2 reviewers; the Oxford quality scoring system was used to evaluate randomization, blinding, withdrawals, and dropouts; and a Mantel-Haenszel random effects pairwise meta-analysis was used to combine data into odds ratios. FINDINGS: The initial search identified 116 trials; 3 of these trials, representing 36,524 patients with stable CAD, met inclusion criteria. According to the pooled results, ivabradine did not consistently reduce all-cause mortality (odds ratio [OR], 1.00 [95% CI, 0.91-1.11]; P = 0.98], cardiovascular death (OR, 1.02 [95% CI, 0.91-1.15]; P = 0.74), or hospitalization for worsening or new onset heart-failure in patients with stable CAD (OR, 0.94 [95% CI, 0.71-1.25]; P = 0.69). Ivabradine did not increase serious adverse drug reactions (OR, 0.99 [95% CI, 0.88-1.13]; P = 0.93) or cardiac disorders (OR, 1.03 [95% CI, 0.87-1.22]; P = 0.74). However, it was associated with drug-specific effects, including new-onset atrial fibrillation (OR, 1.35 [95% CI, 1.19-1.53]; P < 0.001], bradycardia (OR, 6.54 [95% CI, 3.30-12.9]; P < 0.001), phosphenes (OR, 7.77 [95% CI, 4.12-14.63]; P < 0.001), and blurry vision (OR, 3.07 [95% CI, 2.18-4.32]; P < 0.001). IMPLICATIONS: Unselective use of ivabradine in patients with stable CAD is not supported by evidence and can be associated with new-onset atrial fibrillation, bradycardia, and drug-related nuisance adverse events.

Telaprevir versus boceprevir in chronic hepatitis C: a meta-analysis of data from phase II and III trials.

BACKGROUND: Telaprevir and boceprevir are protease inhibitors now added to therapy for patients with chronic hepatitis C virus (HCV) genotype 1 infection who either are treatment naive or have a history of relapse or recurrence following a previous course of treatment with pegylated interferon + ribavirin (Peg-IFN + RBV). Because these agents are fairly new to the market, providers may have limited experience with them in the management of chronic HCV. OBJECTIVE: This meta-analysis compared 24- and 48-week sustained viral responses (SVR) and drug-related adverse events (AEs) between telaprevir and boceprevir triple-therapy regimens in the treatment of chronic HCV infection. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched for articles published from January 1995 to October 2012 on randomized controlled trials that reported SVR at ≥24 weeks in patients with HCV receiving triple-therapy regimens that included telaprevir or boceprevir or placebo + pegylated interferon + ribavirin (Peg-IFN + RBV). Pooled odds ratios (ORs) were calculated and used to compare SVR at 24 and 48 weeks. Secondary end points included common drug-related AEs and treatment discontinuations. RESULTS: Eight studies were included in this meta-analysis (N = 4144 treatment-naive and treatment-experienced patients). With telaprevir, the ORs (95% CI) for SVR at 24 weeks in treatment-naive and treatment-experienced patients were 3.31 (2.27-4.82; P < 0.0001) and 4.21 (1.83-9.72; P = 0.001), respectively. Telaprevir triple therapy did not result in more drug-related discontinuations but did cause additional rash, pruritis, and anemia. With boceprevir, the ORs (95% CI) were improved in both treatment-naive and treatment experienced patients (3.55 [2.66-4.56; P < 0.0001] and 7.34 [3.92-13.9; P < 0.0001]), but with more treatment-related anemia and dysgeusia. CONCLUSIONS: Based on the findings from this meta-analysis, telaprevir or boceprevir combined with Peg-IFN + RBV had favorable short-term data on SVR while resulting in more drug-related AEs. Extended follow-up is required to determine whether these agents offer a reduction in the risk for chronic hepatitis C genotype 1-related mortality and/or hospitalization.

A polypill for all? Critical review of the polypill literature for primary prevention of cardiovascular disease and stroke.

OBJECTIVE: To evaluate the efficacy and safety of the polypill for prevention of cardiovascular disease (CVD) and stroke and to present literature related to the polypill components (statin, aspirin, antihypertensive) for primary prevention of CVD and stroke. DATA SOURCES: A literature search was conducted in MEDLINE (1948-January 2011) and EMBASE (1974-January 2011) using the terms polypill and Polycap. When limited to clinical trials, systematic reviews, or meta-analyses, 7 studies were identified. Bibliographies of pertinent review articles and studies were scanned for additional references. A similar search was conducted to identify literature related to the use of polypill components for primary prevention of CVD and stroke. STUDY SELECTION AND DATA EXTRACTION: Studies that evaluated the hypothetical benefits of a polypill and controlled trials that assessed a formulation of the polypill related to prevention of CVD and stroke were included. Studies were assessed for efficacy, safety, drug interactions, and clinical pharmacokinetics. DATA SYNTHESIS: An initial study to predict benefit estimated that a hypothetical polypill would reduce diastolic blood pressure by 11 mm Hg and low-density lipoprotein cholesterol (LDL-C) by 70 mg/dL, thus reducing the relative risks of CVD and stroke by 88% and 80%, respectively. One clinical trial in patients at low risk for CVD and stroke found that diastolic blood pressure was reduced by 1.6 mm Hg and LDL-C was reduced by 17.7 mg/dL, correlating with 44% and 21% reduction in the relative risks of CVD and stroke, respectively. Studies in higher risk patients reported reductions in systolic blood pressure of up to 28.8 mm Hg and in LDL-C of up to 54 mg/dL, correlating with 62% and 60% relative reduction in risks of CVD and stroke, respectively. CONCLUSIONS: Polypill study results have been more modest than originally theorized. However, results show promise in patients at higher risk for CVD and stroke.