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OBJECTIVETo compare the efficacy and safety of two doses of once-weekly dulaglutide, a glucagon-like peptide 1 receptor agonist, to sitagliptin in uncontrolled, metformin-treated patients with type 2 diabetes. The primary objective was to compare (for noninferiority and then superiority) dulaglutide 1.5 mg versus sitagliptin in change from baseline in glycosylated hemoglobin A1c (HbA1c) at 52 weeks.RESEARCH DESIGN AND METHODSThis multicenter, adaptive, double-blind, parallel-arm study randomized patients (N = 1,098; mean baseline age 54 years; HbA1c 8.1% [65 mmol/mol]; weight 86.4 kg; diabetes duration 7 years) to dulaglutide 1.5 mg, dulaglutide 0.75 mg, sitagliptin 100 mg, or placebo (placebo-controlled period up to 26 weeks). The treatment period lasted 104 weeks, with 52-week primary end point data presented.RESULTSThe mean HbA1c changes to 52 weeks were (least squares mean ± SE): −1.10 ± 0.06% (−12.0 ± 0.7 mmol/mol), −0.87 ± 0.06% (9.5 ± 0.7 mmol/mol), and −0.39 ± 0.06% (4.3 ± 0.7 mmol/mol) for dulaglutide 1.5 mg, dulaglutide 0.75 mg, and sitagliptin, respectively. Both dulaglutide doses were superior to sitagliptin (P < 0.001, both comparisons). No events of severe hypoglycemia were reported. Mean weight changes to 52 weeks were greater with dulaglutide 1.5 mg (−3.03 ± 0.22 kg) and dulaglutide 0.75 mg (−2.60 ± 0.23 kg) compared with sitagliptin (−1.53 ± 0.22 kg) (P < 0.001, both comparisons). The most common gastrointestinal treatment-emergent adverse events in dulaglutide 1.5- and 0.75-mg arms were nausea, diarrhea, and vomiting.CONCLUSIONSBoth dulaglutide doses demonstrated superior glycemic control versus sitagliptin at 52 weeks with an acceptable tolerability and safety profile.

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Type 2 Diabetes Mellitus (HEART2D) is a multinational, randomized, controlled trial designed to compare the effects of prandial versus fasting glycemic control on risk for cardiovascular outcomes in patients with type 2 diabetes after acute myocardial infarction (AMI).RESEARCH DESIGN AND METHODS -Patients (type 2 diabetes, aged 30 -75 years) were randomly assigned within 21 days after AMI to the 1) prandial strategy (PRANDIAL) (three premeal doses of insulin lispro targeting 2-h postprandial blood glucose Ͻ7.5 mmol/l) or the 2) basal strategy (BASAL) (NPH twice daily or insulin glargine once daily targeting fasting/premeal blood glucose Ͻ6.7 mmol/l).RESULTS -A total of 1,115 patients were randomly assigned (PRANDIAL n ϭ 557; BASAL n ϭ 558), and the mean patient participation after randomization was 963 days (range 1-1,687 days). The trial was stopped for lack of efficacy. Risks of first combined adjudicated primary cardiovascular events in the PRANDIAL (n ϭ 174, 31.2%) and BASAL (n ϭ 181, 32.4%) groups were similar (hazard ratio 0.98 [95% CI 0.8 -1.21]). Mean A1C did not differ between the PRANDIAL and BASAL groups (7.7 Ϯ 0.1 vs. 7.8 Ϯ 0.1%; P ϭ 0.4) during the study. The PRANDIAL group showed a lower daily mean postprandial blood glucose (7.8 vs. 8.6 mmol/l; P Ͻ 0.01) and 2-h postprandial blood glucose excursion (0.1 vs. 1.3 mmol/l; P Ͻ 0.001) versus the BASAL group. The BASAL group showed lower mean fasting blood glucose (7.0 vs. 8.1 mmol/l; P Ͻ 0.001) and similar daily fasting/premeal blood glucose (7.7 vs. 7.3 mmol/l; P ϭ 0.233) versus the PRANDIAL group.CONCLUSIONS -Treating diabetic survivors of AMI with prandial versus basal strategies achieved differences in fasting blood glucose, less-than-expected differences in postprandial blood glucose, similar levels of A1C, and no difference in risk for future cardiovascular event rates.

Eli Lilly and Company.