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

Once‐daily initiation of basal insulin as add‐on to metformin: a 26‐week, randomized, treat‐to‐target trial comparing insulin detemir with insulin glargine in patients with type 2 diabetes

ABSTRACT Aims This study assessed the efficacy and safety of once‐daily insulin initiation using insulin detemir (detemir) or insulin glargine (glargine) added to existing metformin in type 2 diabetes (T2D). Methods This 26‐week, multinational, randomized, treat‐to‐target trial involved 457 insulin‐naïve adults with T2D (HbA1c 7–9%). 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) ≤90 mg/dl (≤5.0 mmol/l). Primary efficacy endpoint was change in HbA1c. Results Mean (s.d.) HbA1c decreased with detemir and glargine by 0.48 and 0.74%‐points, respectively, to 7.48% (0.91%) and 7.13% (0.72%) [estimated between‐treatment difference, 0.30 (95% CI: 0.14–0.46)]. Non‐inferiority for detemir at the a priori level of 0.4%‐points was not established. The proportions of patients reaching HbA1c ≤ 7% at 26 weeks were 38% and 53% (p = 0.026) with detemir and glargine, respectively. FPG decreased ∼43.2 mg/dl (∼2.4 mmol/l) in both groups [non‐significant (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 0.54–0.98)]. The proportions of patients reaching HbA1c ≤ 7% without hypoglycaemia in the detemir and glargine groups were 32% and 38% (NS), respectively. Weight decreased with detemir [−0.49 (3.3) kg] and increased with glargine [+1.0 (3.1) kg] (95% CI for difference: −2.17 to −0.89 kg). 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