33 research outputs found
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
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Onceâdaily initiation of basal insulin as addâon to metformin: a 26âweek, randomized, treatâtoâtarget trial comparing insulin detemir with insulin glargine in patients with type 2 diabetes
ABSTRACT
Aims
This study assessed the efficacy and safety of onceâdaily insulin initiation using insulin detemir (detemir) or insulin glargine (glargine) added to existing metformin in type 2 diabetes (T2D).
Methods
This 26âweek, multinational, randomized, treatâtoâtarget trial involved 457 insulinânaĂŻve adults with T2D (HbA1c 7â9%). Detemir or glargine was added to current metformin therapy [any second oral antidiabetic drug (OAD) discontinued] and titrated to a target fasting plasma glucose (FPG) â€90âmg/dl (â€5.0âmmol/l). Primary efficacy endpoint was change in HbA1c.
Results
Mean (s.d.) HbA1c decreased with detemir and glargine by 0.48 and 0.74%âpoints, respectively, to 7.48% (0.91%) and 7.13% (0.72%) [estimated betweenâtreatment difference, 0.30 (95% CI: 0.14â0.46)]. Nonâinferiority for detemir at the a priori level of 0.4%âpoints was not established. The proportions of patients reaching HbA1cââ€â7% at 26âweeks were 38% and 53% (pâ=â0.026) with detemir and glargine, respectively. FPG decreased âŒ43.2âmg/dl (âŒ2.4âmmol/l) in both groups [nonâsignificant (NS)]. Treatment satisfaction was good for both insulins. Hypoglycaemia, which occurred infrequently, was observed less with detemir than glargine [rate ratio 0.73 (95% CI 0.54â0.98)]. The proportions of patients reaching HbA1cââ€â7% without hypoglycaemia in the detemir and glargine groups were 32% and 38% (NS), respectively. Weight decreased with detemir [â0.49 (3.3) kg] and increased with glargine [+1.0 (3.1) kg] (95% CI for difference: â2.17 to â0.89âkg).
Conclusion
While both detemir and glargine, when added to metformin therapy, improved glycaemic control, glargine resulted in greater reductions in HbA1c, while detemir demonstrated less weight gain and hypoglycaemia