The effect of bitter melon (Mormordica charantia) in patients with diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Mormordica charantia (bitter melon) has been investigated for lowering plasma glucose in patients with diabetes mellitus (DM). Previous data has offered inconclusive and inconsistent results about the benefits of bitter melon in patients with DM. Our current project aims to determine whether bitter melon has a favorable effect in lowering plasma glucose in patients with DM. METHODS: We searched PubMed, EMBASE and the Cochrane Library from inception to July 2013 without any language restrictions for randomized controlled trials (RCTs) evaluating bitter melon to no treatment in patients with type 1 or type 2 diabetes. Study selection, data extraction and validity of each article were independently assessed by two investigators. Articles were appraised for proper random sequence generation, allocation concealment, blinding, selective reporting and completeness of outcomes reporting to assess the risk for biases. The glycemic results of each RCT were analyzed to yield weighted mean differences (WMDs) and 95% confidence intervals (CIs). RESULTS: A total of four RCTs, each with 40-66 participants, followed between 4 and 12 weeks were identified in this meta-analysis. Overall risk of bias for each article included was determined to be unclear. In total, 208 participants with type 2 DM (mean age of 56.5 years) were evaluated. Compared with no treatment, bitter melon did not significantly lower A1C (WMD -0.13%, 95% CI -0.41 to 0.16) nor fasting plasma glucose (FPG) 47 (WMD 2.23 mg dl(-1), 95% CI -14.91 to 19.37). CONCLUSIONS: Bitter melon supplementation compared with no treatment did not show significant glycemic improvements on either A1c or FPG.Nutrition & Diabetes advance online publication, 15 December 2014; doi:10.1038/nutd.2014.42.

Early combination therapy for the treatment of type 2 diabetes mellitus: systematic review and meta-analysis.

AIMS: Guidelines for type 2 diabetes recommend add-on agents when metformin alone fails to provide adequate glycaemic control. However, early combination therapy may benefit health outcomes. We conducted a systematic review and meta-analysis to investigate this question. METHODS: We searched MEDLINE and Cochrane CENTRAL (up to July 2012) without language restrictions. We sought randomized controlled trials (RCTs) evaluating initial combination therapy with metformin versus metformin monotherapy in patients with untreated type 2 diabetes. Weighted mean differences (WMDs) for changes from baseline and relative risks (RRs) [with 95% confidence intervals (CIs)] were calculated using random-effects model. RESULTS: In 15 RCTs (N = 6693), the mean age range was 48.4-62.7 years; mean baseline glycosylated haemoglobin (A1c) was 7.2-9.9% and mean diabetes duration was 1.6-4.1 years, with median follow-up of 6 months and with 13 comparisons for A1c change, 14 comparisons for A1c goal attainment of <7% and 13 comparisons for change in fasting plasma glucose (FPG). Drugs combined with metformin included thiazolidinediones (TZDs), insulin secretagogues, dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium glucose transporterase (SGLT-2) inhibitors. Compared to metformin alone, combination therapy with metformin provided statistically significant reductions in A1c (WMD -0.43%, 95% CI -0.56, -0.30), increases in attainment of A1c goal of less than 7% (RR 1.40, 95% CI 1.33-1.48) and reductions in FPG (WMD -14.30 mg/dl, 95% CI -16.09, -12.51). CONCLUSIONS: These results suggest a potential benefit of initial combination therapy on glycaemic outcomes in diabetes compared to metformin monotherapy across a wide range of baseline A1c levels. Further research should explore if early combination treatment may also affect longer term health outcomes in diabetes.

Sulphonylureas and risk of cardiovascular disease: systematic review and meta-analysis.

AIMS: Sulphonylurea use has been linked with increased cardiovascular disease risk; however, previous studies have been inconsistent. Type 2 diabetes independently increases risk for cardiovascular disease, so understanding the link between longer-term use of anti-diabetic medications and cardiovascular disease has important clinical implications. METHODS: Literature search in MEDLINE and CENTRAL was conducted throughout December 2011 for clinical and observational studies that reported the association between sulphonylurea and cardiovascular disease events. Ratios (relative risk, odds ratios or hazard ratios) adjusted for potential confounders (concomitant medications, baseline cardiovascular risk, diabetes severity) were pooled using a random-effects model to yield relative risks and associated 95% confidence intervals. RESULTS: This meta-analysis included 33 studies (n = 1,325,446 patients), followed for a range of 0.46-10.4 years. In all studies, compared with other oral diabetes drugs, sulphonylurea use was associated with a significantly increased risk of cardiovascular death (relative risk 1.27, 95% confidence interval 1.18-1.34, n = 27 comparisons) and composite cardiovascular event (including myocardial infarction, stroke, cardiovascular-related hospitalization or cardiovascular death) (relative risk 1.10, 95% confidence interval 1.04-1.16, n = 43 comparisons). In studies comparing sulphonylurea vs. metformin, these relative risks were 1.26 (95% confidence interval 1.17-1.35, n = 17 comparisons) and 1.18 (95%confidence interval 1.13-1.24, n = 16 comparisons), respectively. CONCLUSIONS: Results suggest that sulphonylurea use may elevate the risk of cardiovascular disease among patients with diabetes. This meta-analysis expands the pool of studies evaluating cardiovascular mortality compared with prior observations while using adjusted estimates, and assessing an additional outcome of a composite cardiovascular event. This finding warrants consideration in clinical practice when other treatment options may be available.

Are the risk factors listed in warfarin prescribing information associated with anticoagulation-related bleeding? A systematic literature review.

Warfarin significantly reduces thromboembolic risk, but perceptions of associated bleeding risk limit its use. The evidence supporting the association between bleeding and individual patient risks factors is unclear. This systematic review aims to determine the strength of evidence supporting an accentuated bleeding risk when patients with risk factors listed in the warfarin prescribing information are prescribed the drug. A systematic literature search of MEDLINE and Cochrane CENTRAL was conducted to identify studies reporting multivariate relationships between prespecified covariates and the risk of bleeding in patients receiving warfarin. The prespecified covariates were identified based on patient characteristics for bleeding listed in the warfarin package insert. Each covariate was evaluated for its association with specific types of bleeding. The quality of individual evaluations was rated as 'good', 'fair' or 'poor' using methods consistent with those recommended by the Agency for Healthcare Research and Quality (AHRQ). Overall strength of evidence was determined using the Grading of Recommendations Assessment, Development (GRADE) criteria and categorised as 'insufficient', 'very low', 'low', 'moderate' or 'high'. Thirty-four studies, reporting 134 multivariate evaluations of the association between a covariate and bleeding risk were identified. The majority of evaluations had a low strength of evidence for the association between covariates and bleeding and none had a high strength of evidence. Malignancy and renal insufficiency were the only two covariates that had a moderate strength of evidence for their association with major and minor bleeding respectively. The associations between covariates listed in the warfarin prescribing information and increased bleeding risk are not well supported by the medical literature.

Oral anti-diabetic drugs for the prevention of Type 2 diabetes.

AIM: To determine the comparative efficacy of oral anti-diabetic drugs in preventing the development of Type 2 diabetes. METHODS: A systematic literature search of MEDLINE, EMBASE and Cochrane CENTRAL was conducted for randomized controlled trials evaluating oral anti-diabetic drugs in patients at high risk for developing Type 2 diabetes. Mixed-treatment comparison meta-analysis methods were used to evaluate the relative risks and risk differences of developing Type 2 diabetes, along with associated 95% credible intervals. RESULTS: Overall, 20 trials (n = 23 230 participants) were included. Upon mixed-treatment comparison meta-analysis, thiazolidinediones, alpha-glucosidase inhibitors and biguanides significantly reduced the relative risk of developing diabetes by 64, 40 and 27%, respectively, compared with control. Sulphonylureas and glinides showed no significant effect. Moreover, thiazolidinediones significantly reduced the relative risk of diabetes by 50% compared with biguanides and trended towards a 40% risk reduction vs. alpha-glucosidase inhibitors [relative risk 0.60 (95% credible intervals 0.34-1.02)]. None of the results were appreciably altered upon subgroup or sensitivity analyses. When evaluating risk differences compared with control, thiazolidinediones (-9%, number needed to treat = 11), alpha-glucosidase inhibitors (-7%, number needed to treat = 14) and biguanides (-7%, number needed to treat = 14) continued to show significant benefit. CONCLUSIONS: Of the oral anti-diabetic drugs evaluated to prevent Type 2 diabetes, thiazolidinediones were associated with the greatest risk reduction compared with control and associated with greater risk reduction than biguanides. Alpha-glucosidase inhibitors and biguanides performed similarly, and better than control, while sulphonylureas and glinides provided no significant benefit.

Statin use and the prevention of venous thromboembolism: a meta-analysis.

AIMS: Statins are thought to have antithrombotic properties and may attenuate patients' odds of developing venous thromboembolism (VTE), but clinical studies have yielded variable estimates of this effect. The aim was to conduct a meta-analysis to evaluate the effect of statin use on development of VTE. METHODS: Randomised controlled trials (RCTs) and observational studies evaluating the effects of statins on the incidence of VTE were selected from MEDLINE (1996 to August 2009), Cochrane CENTRAL (second quarter, 2009), Cochrane Database of Systematic Reviews (second quarter, 2009) and a manual review of references. While no further restrictions were placed on RCTs, observational studies were only included if they reported adjusted effect sizes using appropriate methods. Development of deep vein thrombosis (DVT), pulmonary embolism (PE) and any VTE from RCTs and observational studies were pooled using traditional meta analytic techniques with a random-effects model. RESULTS: Ten studies were identified and eligible for meta-analysis. Upon meta-analysis, statin use was associated with a statistically significant reduction in the odds of developing VTE (AOR 0.68, 95% CI 0.54-0.86), DVT (AOR 0.59, 95% CI 0.43-0.82) and PE (AOR 0.70, 95% CI 0.53-0.94). DISCUSSION: Statin use is associated with significantly reduced odds of developing VTE, DVT or PE by 32%, 41% and 30% respectively. Our meta-analysis included one RCT, JUPITER, which alone provided statistically significant reduction in the odds of developing VTE and DVT (43% and 55% respectively), and a nonsignificant reduction on PE. CONCLUSION: Currently available evidence suggests that statins can reduce patients' odds of developing VTE.