Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3).
OBJECTIVE
Compare the efficacy and safety of monotherapy with dulaglutide, a once-weekly GLP-1 receptor agonist, to metformin-treated patients with type 2 diabetes. The primary objective compared dulaglutide 1.5 mg and metformin on change from baseline glycosylated hemoglobin A1c (HbA1c) at 26 weeks.


METHODS
This 52-week double-blind study randomized patients to subcutaneous dulaglutide 1.5 mg, dulaglutide 0.75 mg, or metformin. Patients (N = 807) had HbA1c ≥6.5% (≥48 mmol/mol) and ≤9.5% (≤80 mmol/mol) with diet and exercise alone or low-dose oral antihyperglycemic medication (OAM) monotherapy; OAMs were discontinued at beginning of lead-in period.


RESULTS
At 26 weeks, changes from baseline HbA1c (least squares [LS] mean ± SE) were: dulaglutide 1.5 mg, -0.78 ± 0.06% (-8.5 ± 0.70 mmol/mol); dulaglutide 0.75 mg, -0.71 ± 0.06% (-7.8 ± 0.70 mmol/mol); and metformin, -0.56 ± 0.06% (-6.1 ± 0.70 mmol/mol). Dulaglutide 1.5 and 0.75 mg were superior to metformin (LS mean difference): -0.22% (-2.4 mmol/mol) and -0.15% (-1.6 mmol/mol) (one-sided P < 0.025, both comparisons), respectively. Greater percentages reached HbA1c targets <7.0% (<53 mmol/mol) and ≤6.5% (≤48 mmol/mol) with dulaglutide 1.5 and 0.75 mg compared with metformin (P < 0.05, all comparisons). No severe hypoglycemia was reported. Compared with metformin, decrease in weight was similar with dulaglutide 1.5 mg and smaller with dulaglutide 0.75 mg. Over 52 weeks, nausea, diarrhea, and vomiting were the most common adverse events; incidences were similar between dulaglutide and metformin.


CONCLUSIONS
Dulaglutide improves glycemic control and is well tolerated as monotherapy in patients with early stage type 2 diabetes.
Division of Endocrinology, Emory University School of Medicine, Atlanta, GA.
Guillermo
G
Umpierrez
Endocrinología, Clínica Juaneda, Palma de Mallorca, Spain.
Santiago
S
Tofé Povedano
Centro de Investigaciones Metabólicas, Buenos Aires, Argentina.
Federico
F
Pérez Manghi
Lilly Diabetes, Eli Lilly and Company, Indianapolis, IN.
Linda
L
Shurzinske
Lilly Diabetes, Eli Lilly and Company, Neuilly-sur-Seine Cedex, France pechtner_valeria@lilly.com.
Valeria
V
Pechtner
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D004763:Glucagon-Like Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D001786:Blood Glucose; D004763:Glucagon-Like Peptides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D008687:Metformin; D011993:Recombinant Fusion Proteins; C555680:dulaglutide