Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Predicting parasite dynamics in mixed-use trans-Himalayan pastures to underpin management of cross-transmission between livestock and bharal

The complexities of multi-use landscapes require sophisticated approaches to addressing disease transmission risks. We explored gastro-intestinal nematode (GINs) infections in the North India Trans-Himalayas through a socio-ecological lens, integrating parasite transmission modelling with field surveys and local knowledge, and evaluated the likely effectiveness of potential interventions. Bharal (blue sheep; Pseudois nayaur), a native wild herbivore, and livestock share pasture year-round and livestock commonly show signs of GINs infection. While both wild and domestic ungulates had GINs infections, egg counts indicated significantly higher parasite burdens in bharal than livestock. However, due to higher livestock densities, they contributed more to the total count of eggs and infective larvae on pasture. Herders also reported health issues in their sheep and goats consistent with parasite infections. Model simulations suggested that pasture infectivity in this system is governed by historical pasture use and gradually accumulated larval development during the summer, with no distinct short-term flashpoints for transmission. The most effective intervention was consequently predicted to be early-season parasite suppression in livestock using temperature in spring as a cue. A 1-month pause in egg output from livestock could lead to a reduction in total annual availability of infective larvae on pasture of 76%, potentially benefitting the health of both livestock and bharal. Modelling suggested that climate change over the past 33 years has led to no overall change in GINs transmission potential, but an increase in the relative influence of temperature over precipitation in driving pasture infectivity. Our study provides a transferable multi-pronged approach to investigating disease transmission, in order to support herders' livelihoods and conserve wild ungulates