Monotherapy with the once-weekly GLP-1 analogue dulaglutide for 12 weeks in patients with Type 2 diabetes: dose-dependent effects on glycaemic control in a randomized, double-blind, placebo-controlled study.
OBJECTIVE
Evaluate dose-dependent effects of once-weekly dulaglutide, a glucagon-like peptide-1 analogue, on glycaemic control in patients with Type 2 diabetes treated with lifestyle measures with or without previous metformin.


METHODS
This 12-week, double-blind, placebo-controlled, dose-response trial randomized 167 patients who were anti-hyperglycaemic medication-naïve or had discontinued metformin monotherapy [mean baseline HbA(1c) 59 ± 8 to 61 ± 8 mmol/mol (7.6 ± 0.7 to 7.8 ± 0.8%)] to once-weekly injections of placebo or dulaglutide (0.1, 0.5, 1.0 or 1.5 mg).


RESULTS
A significant dose-dependent reduction in HbA(1c) (least squares mean ± SE) was observed across doses (P < 0.001). HbA(1c) reductions in the 0.5, 1.0 and 1.5 mg dulaglutide groups were greater than in the placebo group [-10 ± 1, -11 ± 1 and -11 ± 1 vs. 0 ± 1 mmol/mol (-0.9 ± 0.1, -1.0 ± 0.1 and -1.0 ± 0.1 vs. 0.0 ± 0.1%), respectively, all P < 0.001]. Dose-dependent reductions in fasting plasma glucose were also observed [least squares mean difference (95% CI) ranging from -0.43 (-1.06 to 0.19) mmol/l for dulaglutide 0.1 mg to -1.87 (-2.56 to -1.19) mmol/l for dulaglutide 1.5 mg, P < 0.001]. Dose-dependent weight loss was demonstrated across doses (P = 0.009), but none of the groups were different from placebo. The most common adverse events were nausea and diarrhoea.


CONCLUSIONS
The observed dulaglutide dose-dependent reduction in HbA(1c) and its acceptable safety profile support further clinical development for treatment of Type 2 diabetes.
Grunberger Diabetes Institute, Bloomfield Hills, MI, USA.
G
G
Grunberger
A
A
Chang
G
G
Garcia Soria
F T
FT
Botros
R
R
Bsharat
Z
Z
Milicevic
D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005215:Fasting / Q000097:blood; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D004763:Glucagon-Like Peptides / Q000031:analogs & derivatives; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; C555680:dulaglutide