Real-world studies have become increasingly important in providing evidence of treatment effectiveness in clinical practice. While randomized clinical trials (RCTs) are the “gold standard” for evaluating the safety and efficacy of new therapeutic agents, necessarily strict inclusion and exclusion criteria mean that trial populations are often not representative of the patient populations encountered in clinical practice. Real-world studies may use information from electronic health and claims databases, which provide large datasets from diverse patient populations, and/or may be observational, collecting prospective or retrospective data over a long period of time. They can therefore provide information on the long-term safety, particularly pertaining to rare events, and effectiveness of drugs in large heterogeneous populations, as well as information on utilization patterns and health and economic outcomes. This review focuses on how evidence from real-world studies can be utilized to complement data from RCTs to gain a more complete picture of the advantages and disadvantages of medications as they are used in practice.Funding: Sanofi US, Inc.

To investigate the efficacy, safety, and tolerability of oral semaglutide added to insulin with or without metformin. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes uncontrolled on insulin with or without metformin were randomized to oral semaglutide 3 mg (N 5 184), 7 mg (N 5 182), or 14 mg (N 5 181) or to placebo (N 5 184) in a 52-week, double-blind trial. End points were change from baseline to week 26 in HbA 1c (primary) and body weight (confirmatory secondary). Two estimands were defined: treatment policy (effect regardless of trial product discontinuation or rescue medication) and trial product (effect assuming trial product continuation without rescue medication) in randomized patients. RESULTS Oral semaglutide was superior to placebo in reducing HbA 1c (estimated treatment difference [ETD]-0.5% [95%

OBJECTIVE:To conduct a randomised trial of a physical activity (PA) intervention, The First Step Program (FSP) for adults with type II diabetes. DESIGN: A 16-week intervention study and 24-week follow-up assessment. PARTICIPANTS: A total of 47 overweight/obese, sedentary individuals (age ¼ 52.775.2 y; BMI ¼ 33.375.6 kg/m 2 ) recruited through a diabetes education centre. MEASUREMENTS: Primary outcome: daily PA assessed by pedometer (steps/day). Secondary outcomes: anthropometric measures (weight, BMI, waist girth, hip girth); indicators of cardiovascular health (resting heart rate and blood pressure); glycemic control (fasting glucose, insulin, HbA1c, glucose concentration 120 min postglucose load); plasma lipid status (total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides). RESULTS: Relative to the CONTROL group, FSP participants increased their PA 43000 steps/day (approximately 30 min/day) during the intervention (Po0.0001). Waist and hip girth decreased (approximately 2-3 cm), but did not differ significantly between groups. Significant changes did not emerge for any of the other variables. CONCLUSIONS: The FSP is a practical intervention that elicits an immediate and profound change in walking behaviour. Such change is an important 'first step' towards increasing the volume and/or intensity of PA necessary to improve long-term health outcomes in this largely sedentary and overweight or obese population. Relapse by 24 weeks indicates that other strategies such as booster sessions are needed to maintain lifestyle change. Further research must determine realistic and responsive health outcomes for this population that are achievable through practical, real-world programming.

OBJECTIVETo examine cross-sectional associations of serum vitamin D [25-hydroxyvitamin D, 25(OH)D] concentration with insulin resistance (IR) and β-cell dysfunction in 712 subjects at risk for type 2 diabetes.RESEARCH DESIGN AND METHODSSerum 25(OH)D was determined using a chemiluminescence immunoassay. Insulin sensitivity/resistance were measured using the Matsuda insulin sensitivity index for oral glucose tolerance tests (ISOGTT) and homeostasis model assessment of insulin resistance HOMA-IR. β-Cell function was determined using both the insulinogenic index (IGI) divided by HOMA-IR (IGI/IR) and the insulin secretion sensitivity index-2 (ISSI-2).RESULTSLinear regression analyses indicated independent associations of 25(OH)D with ISOGTT and HOMA-IR (β = 0.004, P = 0.0003, and β = −0.003, P = 0.0072, respectively) and with IGI/IR and ISSI-2 (β = 0.004, P = 0.0286, and β = 0.003, P = 0.0011, respectively) after adjusting for sociodemographics, physical activity, supplement use, parathyroid hormone, and BMI.CONCLUSIONSVitamin D may play a role in the pathogenesis of type 2 diabetes, as 25(OH)D concentration was independently associated with both insulin sensitivity and β-cell function among individuals at risk of type 2 diabetes.