Phase 3 trials have not compared oral semaglutide, a glucagon-like peptide 1 receptor agonist, with other classes of glucose-lowering therapy. OBJECTIVE To compare efficacy and assess long-term adverse event profiles of once-daily oral semaglutide vs sitagliptin, 100 mg added on to metformin with or without sulfonylurea, in patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, double-dummy, parallel-group, phase 3a trial conducted at 206 sites in 14 countries over 78 weeks from February 2016 to March 2018. Of 2463 patients screened, 1864 adults with type 2 diabetes uncontrolled with metformin with or without sulfonylurea were randomized. INTERVENTIONS Patients were randomized to receive once-daily oral semaglutide, 3 mg (n = 466), 7 mg (n = 466), or 14 mg (n = 465), or sitagliptin, 100 mg (n = 467). Semaglutide was initiated at 3 mg/d and escalated every 4 weeks, first to 7 mg/d then to 14 mg/d, until the randomized dosage was achieved. MAIN OUTCOMES AND MEASURES The primary end point was change in glycated hemoglobin (HbA 1c), and the key secondary end point was change in body weight, both from baseline to week 26. Both were assessed at weeks 52 and 78 as additional secondary end points. End points were tested for noninferiority with respect to HbA 1c (noninferiority margin, 0.3%) prior to testing for superiority of HbA 1c and body weight. RESULTS Among 1864 patients randomized (mean age, 58 [SD, 10] years; mean baseline HbA 1c , 8.3% [SD, 0.9%]; mean body mass index, 32.5 [SD, 6.4]; n=879 [47.2%] women), 1758 (94.3%) completed the trial and 298 prematurely discontinued treatment (16.7% for semaglutide, 3 mg/d; 15.0% for semaglutide, 7 mg/d; 19.1% for semaglutide, 14 mg/d; and 13.1% for sitagliptin). Semaglutide, 7 and 14 mg/d, compared with sitagliptin, significantly reduced HbA 1c (differences,-0.3% [95% CI,-0.4% to-0.1%] and-0.5% [95% CI,-0.6% to-0.4%], respectively; P < .001 for both) and body weight (differences,-1.6 kg [95% CI,-2.0 to-1.1 kg] and-2.5 kg [95% CI,-3.0 to-2.0 kg], respectively; P < .001 for both) from baseline to week 26. Noninferiority of semaglutide, 3 mg/d, with respect to HbA 1c was not demonstrated. Week 78 reductions in both end points were statistically significantly greater with semaglutide, 14 mg/d, vs sitagliptin. CONCLUSIONS AND RELEVANCE Among adults with type 2 diabetes uncontrolled with metformin with or without sulfonylurea, oral semaglutide, 7 mg/d and 14 mg/d, compared with sitagliptin, resulted in significantly greater reductions in HbA 1c over 26 weeks, but there was no significant benefit with the 3-mg/d dosage. Further research is needed to assess effectiveness in a clinical setting.

Objectives To examine 25 year trends in first time hospitalisation for acute myocardial infarction in Denmark, subsequent short and long term mortality, and the prognostic impact of sex and comorbidity.Design Nationwide population based cohort study using medical registries. Setting All hospitals in Denmark.Subjects 234 331 patients with a first time hospitalisation for myocardial infarction from 1984 through 2008. Main outcome measuresStandardised incidence rate of myocardial infarction and 30 day and 31-365 day mortality by sex. Comorbidity categories were defined as normal, moderate, severe, and very severe according to the Charlson comorbidity index, and were compared by means of mortality rate ratios based on Cox regression.Results The standardised incidence rate per 100 000 people decreased in the 25 year period by 37% for women (from 209 to 131) and by 48% for men (from 410 to 213). The 30 day, 31-365 day, and one year mortality declined from 31.4%, 15.6%, and 42.1% in 1984-8 to 14.8%, 11.1%, and 24.2% in 2004-8, respectively. After adjustment for age at time of myocardial infarction, men and women had the same one year risk of dying. The mortality reduction was independent of comorbidity category. Comparing patients with very severe versus normal comorbidity during 2004-8, the mortality rate ratio, adjusted for age and sex, was 1.96 (95% CI 1.83 to 2.11) within 30 days and 3.89 (3.58 to 4.24) within 31-365 days. ConclusionsThe rate of first time hospitalisation for myocardial infarction and subsequent short term mortality both declined by nearly half between 1984 and 2008. The reduction in mortality occurred for all patients, independent of sex and comorbidity. However, comorbidity burden was a strong prognostic factor for short and long term mortality, while sex was not.

Bone metastasis and skeletal related events predict poor prognosis in men with prostate cancer.

Short- and long-term mortality improved considerably between 1994 and 2011 for all types of stroke. Short-term mortality improved regardless of comorbidity burden. However, comorbidity burden was a strong prognostic factor for both short- and long-term mortality.