Randomized, Double-Blind Trial of Triple Therapy With Saxagliptin Add-on to Dapagliflozin Plus Metformin in Patients With Type 2 Diabetes.
OBJECTIVE
The objective of this study was to assess the efficacy and safety of triple therapy with saxagliptin add-on versus placebo add-on to dapagliflozin plus metformin in adults with type 2 diabetes.


METHODS
Patients on stable metformin (≥1,500 mg/day) for ≥8 weeks with glycated hemoglobin (HbA1c) 8.0-11.5% (64-102 mmol/mol) at screening received open-label dapagliflozin (10 mg/day) plus metformin immediate release (IR) for 16 weeks. Patients with inadequate glycemic control (HbA1c 7-10.5% [53-91 mmol/mol]) were then randomized to receive placebo (n = 153) or saxagliptin 5 mg/day (n = 162) in addition to background dapagliflozin plus metformin IR. The primary efficacy end point was change in HbA1c from baseline to week 24.


RESULTS
There was a significantly greater reduction in HbA1c at 24 weeks with saxagliptin add-on (-0.51% [-5.6 mmol/mol]) versus placebo (-0.16% [-1.7 mmol/mol]) add-on to dapagliflozin plus metformin (difference, -0.35% [95% CI -0.52% to -0.18%] and -3.8 [-5.7 to -2.0 mmol/mol], respectively; P < 0.0001). Reductions in fasting plasma glucose and 2-h postprandial glucose were similar between treatment arms. A larger proportion of patients achieved HbA1c <7% (53 mmol/mol) with saxagliptin add-on (35.3%) versus placebo add-on (23.1%) to dapagliflozin plus metformin. Adverse events were similar between treatment groups. Episodes of hypoglycemia were infrequent in both treatment arms, and there were no episodes of major hypoglycemia.


CONCLUSIONS
Triple therapy with the addition of saxagliptin to dapagliflozin plus metformin was well tolerated and produced significant improvements in HbA1c in patients with type 2 diabetes inadequately controlled with dapagliflozin plus metformin.
Diabetes-Zentrum, Quakenbrück, Germany s.matthaei@ckq-gmbh.de.
Stephan
S
Matthaei
Spitalul Clinic Judetean de Urgenta Constanta, Constanta, Romania.
Doina
D
Catrinoiu
CenterMed-Centrum Badań Klinicznych, Kraków, Poland.
Aleksander
A
Celiński
AstraZenenca, Mölndal, Sweden.
Ella
E
Ekholm
AstraZeneca, Gaithersburg, MD.
William
W
Cook
MedImmune, Gaithersburg, MD.
Boaz
B
Hirshberg
AstraZeneca, Gaithersburg, MD.
Hungta
H
Chen
Bristol-Myers Squibb, Princeton, NJ.
Nayyar
N
Iqbal
Bristol-Myers Squibb, Princeton, NJ.
Lars
L
Hansen
D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology; D004151:Dipeptides / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005960:Glucosides / Q000008:administration & dosage* / Q000009:adverse effects; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D016896:Treatment Outcome
D000218:Adamantane; D001559:Benzhydryl Compounds; D001786:Blood Glucose; D004151:Dipeptides; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; C529054:dapagliflozin; C502994:saxagliptin