Background Given the increase in medications for type 2 diabetes mellitus, clinicians and patients need information about their effectiveness and safety to make informed choices. Purpose To summarize the benefits and harms of metformin, second-generation sulfonylureas, thiazolidinediones, meglitinides, dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon-like peptide-1 receptor agonists, as monotherapy and in combination, to treat adults with type 2 diabetes. Data Sources MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception through April 2010 for English-language observational studies and trials. The MEDLINE search was updated to December 2010 for long-term clinical outcomes. Study Selection Two reviewers independently screened reports and identified 140 trials and 26 observational studies of head-to-head comparisons of monotherapy or combination therapy that reported intermediate or long-term clinical outcomes or harms. Data Extraction Two reviewers following standardized protocols serially extracted data, assessed applicability, and independently evaluated study quality. Data Synthesis Evidence on long-term clinical outcomes (all-cause mortality, cardiovascular disease, nephropathy, and neuropathy) was of low strength or insufficient. Most medications decreased the hemoglobin A1c level by about 1 percentage point and most 2-drug combinations produced similar reductions. Metformin was more efficacious than the DPP-4 inhibitors, and compared with thiazolidinediones or sulfonylureas, the mean differences in body weight were about −2.5 kg. Metformin decreased low-density lipoprotein cholesterol levels compared with pioglitazone, sulfonylureas, and DPP-4 inhibitors. Sulfonylureas had a 4-fold higher risk for mild or moderate hypoglycemia than metformin alone and, in combination with metformin, had more than a 5-fold increased risk compared with metformin plus thiazolidinediones. Thiazolidinediones increased risk for congestive heart failure compared with sulfonylureas and increased risk for bone fractures compared with metformin. Diarrhea occurred more often with metformin than with thiazolidinediones. Limitations Only English-language publications were reviewed. Some studies may have selectively reported outcomes. Many studies were small, were of short duration, and had limited ability to assess clinically important harms and benefits. Conclusion Evidence supports metformin as a first-line agent to treat type 2 diabetes. Most 2-drug combinations similarly reduce hemoglobin A1c levels, but some increased risk for hypoglycemia and other adverse events. Primary Funding Source Agency for Healthcare Research and Quality.

BACKGROUNDObservational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of type 2 diabetes. However, whether vitamin D supplementation lowers the risk of diabetes is unknown. METHODSWe randomly assigned adults who met at least two of three glycemic criteria for prediabetes (fasting plasma glucose level, 100 to 125 mg per deciliter; plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter; and glycated hemoglobin level, 5.7 to 6.4%) and no diagnostic criteria for diabetes to receive 4000 IU per day of vitamin D 3 or placebo, regardless of the baseline serum 25-hydroxyvitamin D level. The primary outcome in this time-to-event analysis was new-onset diabetes, and the trial design was event-driven, with a target number of diabetes events of 508. RESULTSA total of 2423 participants underwent randomization (1211 to the vitamin D group and 1212 to the placebo group). By month 24, the mean serum 25-hydroxyvitamin D level in the vitamin D group was 54.3 ng per milliliter (from 27.7 ng per milliliter at baseline), as compared with 28.8 ng per milliliter in the placebo group (from 28.2 ng per milliliter at baseline). After a median follow-up of 2.5 years, the primary outcome of diabetes occurred in 293 participants in the vitamin D group and 323 in the placebo group (9.39 and 10.66 events per 100 person-years, respectively). The hazard ratio for vitamin D as compared with placebo was 0.88 (95% confidence interval, 0.75 to 1.04; P = 0.12). The incidence of adverse events did not differ significantly between the two groups. CONCLUSIONSAmong persons at high risk for type 2 diabetes not selected for vitamin D insufficiency, vitamin D 3 supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; D2d ClinicalTrials.gov number, NCT01942694.)A BS TR AC T

The PCMH holds promise for improving the experiences of patients and staff and potentially for improving care processes,but current evidence is insufficient to determine effects on clinical and most economic outcomes

Background: Atrial fibrillation (AF) is a common cardiac arrhythmia that increases the risk of stroke. Medical therapy for decreasing stroke risk involves anticoagulation, which may increase bleeding risk for certain patients. In determining optimal therapy for stroke prevention for patients with AF, clinicians use tools with various clinical, imaging, and patient characteristics to weigh stroke risk against therapy-associated bleeding risk. Aim: Review published literature and summarize available risk stratification tools for stroke and bleeding prediction in patients with AF. Methods: We searched for English-language studies in PubMed®, Embase®, and the Cochrane Database of Systematic Reviews published between January 1, 2000, and February 14, 2018. Two reviewers screened citations for studies that examined tools for predicting thromboembolic and bleeding risks in patients with AF. Data regarding study design, patient characteristics, interventions, outcomes, quality and applicability were extracted. Results: 61 studies were relevant to predicting thromboembolic risk and 38 to predicting bleeding risk. Data suggest that CHADS2, CHA2DS2-VASc, and ABC risk scores have the best evidence predicting thromboembolic risk (moderate strength of evidence for limited prediction ability of each score) and that HAS-BLED has the best evidence for predicting bleeding risk (moderate strength of evidence). Limitations: Studies were heterogeneous in methodology and populations of interest, setting, interventions, and outcomes analyzed. Conclusion: CHADS2, CHA2DS2-VASc, and ABC stroke have the best prediction for stroke events, and HAS-BLED provides the best prediction for bleeding risk. Future studies should define the role of imaging tools and biomarkers in enhancing the accuracy of risk prediction tools. Primary Funding Source: Patient-Centered Outcomes Research Institute (PROSPERO #CRD42017069999)

Background Serum potassium levels affect insulin secretion by pancreatic beta-cells, and hypokalemia associated with diuretic use has been associated with dysglycemia. We hypothesized that adults with lower serum potassium levels and lower dietary potassium intake are at higher risk for incident diabetes, independent of diuretic use. Methods We analyzed data from 12,209 participants from the Atherosclerosis Risk in Communities (ARIC) Study, an on-going prospective cohort study beginning in 1986, with 9 years of in-person follow-up and 17 years of telephone follow-up. Using multivariate Cox proportional hazard models, we estimated the relative hazard (RH) of incident diabetes associated with baseline serum potassium levels. Results During 9 years of in-person follow-up, 1475 participants developed incident diabetes. In multivariate analyses, we found an inverse association between serum potassium and risk of incident diabetes. Compared to those with a high-normal serum potassium (5.0-5.5 mEq/l), adults with serum potassium levels of < 4.0, 4.0-<4.5, and 4.5-<5.0, (mEq/L) had adjusted relative hazards (RH) (95% CI) of incident diabetes of 1.64 (1.29-2.08), 1.64 (1.34-2.01), and 1.39 (1.14-1.71) respectively. An increased risk persisted during an additional 8 years of telephone follow-up based on self-report with RHs of 1.2-1.3 for those with a serum potassium less than 5.0 mEq/L. Dietary potassium intake was significantly associated with risk of incident diabetes in unadjusted models but not in multivariate models. Conclusions Serum potassium is an independent predictor of incident diabetes in this cohort. Further study is needed to determine if modification of serum potassium could reduce the subsequent risk of diabetes.