Alpha-glucosidase inhibitors for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus.

BACKGROUND: Alpha-glucosidase inhibitors (AGI) reduce blood glucose levels and may thus prevent or delay type 2 diabetes mellitus (T2DM) and its associated complications in people at risk of developing of T2DM. OBJECTIVES: To assess the effects of AGI in people with impaired glucose tolerance (IGT), impaired fasting blood glucose (IFG), moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and the reference lists of systematic reviews, articles and health technology assessment reports. The date of the last search of all databases was December 2017. SELECTION CRITERIA: We included randomised controlled trials (RCTs), with a duration of one year or more, comparing AGI with any pharmacological glucose-lowering intervention, behaviour-changing intervention, placebo or no intervention in people with IFG, IGT, moderately elevated HbA1c or combinations of these. DATA COLLECTION AND ANALYSIS: Two review authors read all abstracts and full-text articles or records, assessed quality and extracted outcome data independently. One review author extracted data, which were checked by a second review author. We resolved discrepancies by consensus or involvement of a third review author. For meta-analyses we used a random-effects model with assessment of risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We assessed the overall quality of the evidence by using the GRADE instrument. MAIN RESULTS: For this update of the Cochrane Review (first published 2006, Issue 4) we included 10 RCTs (11,814 participants), eight investigating acarbose and two investigating voglibose, that included people with IGT or people "at increased risk for diabetes". The trial duration ranged from one to six years. Most trials compared AGI with placebo (N = 4) or no intervention (N = 4).Acarbose reduced the incidence of T2DM compared to placebo: 670 out of 4014 people (16.7%) in the acarbose groups developed T2DM, compared to 812 out of 3994 people (20.3%) in the placebo groups (RR 0.82, 95% CI 0.75 to 0.89; P < 0.0001; 3 trials; 8008 participants; moderate-certainty evidence). One trial including participants with coronary heart disease and IGT contributed 64% of cases for this outcome. Acarbose reduced the risk of T2DM compared to no intervention: 7 out 75 people (9.3%) in the acarbose groups developed T2DM, compared to 18 out of 65 people (27.7%) in the no-intervention groups (RR 0.31, 95% CI 0.14 to 0.69; P = 0.004; 2 trials; 140 participants; very low-certainty evidence).Acarbose compared to placebo did not reduce or increase the risk of all-cause mortality (RR 0.98, 95% CI 0.82 to 1.18; P = 0.86; 3 trials; 8069 participants; very low-certainty evidence), cardiovascular mortality (RR 0.88; 95% CI 0.71 to 1.10; P = 0.26; 3 trials; 8069 participants; very low-certainty evidence), serious adverse events (RR 1.12, 95% CI 0.97 to 1.29; P = 0.13; 2 trials; 6625 participants; low-certainty evidence), non-fatal stroke (RR 0.50, 95% CI 0.09 to 2.74; P = 0.43; 1 trial; 1368 participants; very low-certainty evidence) or congestive heart failure (RR of 0.87; 95% CI 0.63 to 1.12; P = 0.40; 2 trials; 7890 participants; low-certainty evidence). Acarbose compared to placebo reduced non-fatal myocardial infarction: one out of 742 participants (0.1%) in the acarbose groups had a non-fatal myocardial infarction compared to 15 out of 744 participants (2%) in the placebo groups (RR 0.10, 95% CI 0.02 to 0.53; P = 0.007; 2 trials; 1486 participants; very low-certainty evidence). Acarbose treatment showed an increased risk of non-serious adverse events (mainly gastro-intestinal events), compared to placebo: 751 of 775 people (96.9%) in the acarbose groups experienced an event, compared to 723 of 775 people (93.3%) in the placebo groups (RR 1.04; 95% CI 1.01 to 1.06; P = 0.0008; 2 trials; 1550 participants). Acarbose compared to no intervention showed no advantage or disadvantage for any of these outcome measures (very low-certainty evidence).One trial each compared voglibose with placebo (1780 participants) or diet and exercise (870 participants). Voglibose compared to placebo reduced the incidence of T2DM: 50 out of 897 participants (5.6%) developed T2DM, compared to 106 out of 881 participants (12%) in the placebo group (RR 0.46, 95% CI 0.34 to 0.64; P < 0.0001; 1 trial; 1778 participants; low-certainty evidence). For all other reported outcome measures there were no clear differences between voglibose and comparator groups. One trial with 90 participants compared acarbose with diet and exercise and another trial with 98 participants reported data on acarbose versus metformin. There were no clear differences for any outcome measure between these two acarbose interventions and the associated comparator groups.None of the trials reported amputation of lower extremity, blindness or severe vision loss, end-stage renal disease, health-related quality of life, time to progression to T2DM, or socioeconomic effects. AUTHORS' CONCLUSIONS: AGI may prevent or delay the development of T2DM in people with IGT. There is no firm evidence that AGI have a beneficial effect on cardiovascular mortality or cardiovascular events.

Performance of the SCORE and Globorisk cardiovascular risk prediction models: a prospective cohort study in Dutch general practice.

BACKGROUND: GPs frequently use 10-year-risk estimations of cardiovascular disease (CVD) to identify high- risk patients. AIM: To assess the performance of four models for predicting the 10-year risk of CVD in Dutch general practice. DESIGN AND SETTING: Prospective cohort study. Routine data (2009- 2019) was used from 46 Dutch general practices linked to cause of death statistics. METHOD: The outcome measures were fatal CVD for SCORE and first diagnosis of fatal or non- fatal CVD for SCORE fatal and non-fatal (SCORE- FNF), Globorisk-laboratory, and Globorisk-office. Model performance was assessed by examining discrimination and calibration. RESULTS: The final number of patients for risk prediction was 1981 for SCORE and SCORE-FNF, 3588 for Globorisk-laboratory, and 4399 for Globorisk- office. The observed percentage of events was 18.6% (n = 353) for SCORE- FNF, 6.9% (n = 230) for Globorisk-laboratory, 7.9% (n = 323) for Globorisk-office, and 0.3% (n = 5) for SCORE. The models showed poor discrimination and calibration. The performance of SCORE could not be examined because of the limited number of fatal CVD events. SCORE-FNF, the model that is currently used for risk prediction of fatal plus non-fatal CVD in Dutch general practice, was found to underestimate the risk in all deciles of predicted risks. CONCLUSION: Wide eligibility criteria and a broad outcome measure contribute to the model applicability in daily practice. The restriction to fatal CVD outcomes of SCORE renders it less usable in routine Dutch general practice. The models seriously underestimate the 10-year risk of fatal plus non-fatal CVD in Dutch general practice. The poor model performance is possibly because of differences between patients that are eligible for risk prediction and the population that was used for model development. In addition, selection of higher-risk patients for CVD risk assessment by GPs may also contribute to the poor model performance.

Prevalence of primary aldosteronism in primary care: a cross-sectional study.

BACKGROUND: Primary aldosteronism (PA) is the most frequent cause of secondary hypertension. Reported prevalences of PA vary considerably because of a large heterogeneity in study methodology. AIM: To examine the proportion of patients with PA among patients with newly diagnosed, never treated hypertension. DESIGN AND SETTING: A cross-sectional study set in primary care. METHOD: GPs measured aldosterone and renin in adult patients with newly diagnosed, never treated hypertension. Patients with elevated aldosterone-to-renin ratio and increased plasma aldosterone concentration underwent a saline infusion test to confirm or exclude PA. The source population was meticulously assessed to detect possible selection bias. RESULTS: Of 3748 patients with newly diagnosed hypertension, 343 patients were screened for PA. In nine out of 74 patients with an elevated aldosterone-to-renin ratio and increased plasma aldosterone concentration the diagnosis of PA was confirmed by a saline infusion test, resulting in a prevalence of 2.6% (95% confidence interval = 1.4 to 4.9). All patients with PA were normokalaemic and 8 out of 9 patients had sustained blood pressure >150/100 mmHg. Screened patients were younger (P<0.001) or showed higher blood pressure (P<0.001) than non-screened patients. CONCLUSION: In this study a prevalence of PA of 2.6% in a primary care setting was established, which is lower than estimates reported from other primary care studies so far. This study supports the screening strategy as recommended by the Endocrine Society Clinical Practice Guideline. The low proportion of screened patients (9.2%), of the large cohort of eligible patients, reflects the difficulty of conducting prevalence studies in primary care clinical practice.