Long-term effects of dapagliflozin plus saxagliptin versus glimepiride on a background of metformin in patients with type 2 diabetes: Results of a 104-week extension to a 52-week randomized, phase 3 study and liver fat MRI substudy
Journal article, 2022

Aim:
To report the results of a 104-week extension to a 52-week study in which dapagliflozin plus saxagliptin (DAPA+SAXA) improved glycaemic control, liver fat and metabolic variables compared with glimepiride (GLIM) in participants with type 2 diabetes (T2D) receiving background metformin.
Materials and methods:
This extension to a 52-week global, multicentre, parallel-group, active-controlled, double-blind study (NCT02419612) continued randomized participants (1:1) on DAPA+SAXA (10/5 mg) plus placebo, or GLIM (1-6 mg) plus placebo, once daily. Eligible participants were aged ≥18 years, had T2D (glycated haemoglobin [HbA1c] 58.5-91.3 mmol/mol [7.5%-10.5%]), and a body mass index of 20.0 to 45.0 kg/m2, and were receiving metformin (MET; ≥1500 mg/d).
Key outcomes were:
requirement for treatment intensification, based on HbA1c ≥53 mmol/mol (7%); achieving therapeutic glycaemic response; and changes in adipose tissue and liver fat on magnetic resonance imaging in a substudy.
Results:
Overall, 382 participants entered and 338 completed the 104-week extension period (MRI substudy, n = 82). The need for treatment intensification during the 156-week period was lower for DAPA+SAXA+MET (37.0%) than GLIM+MET (55.6%; hazard ratio 0.52, 95% confidence interval [CI] 0.39-0.68; P < 0.001). At week 156, 21.4% of DAPA+SAXA+MET versus 11.7% of GLIM+MET participants achieved therapeutic glycaemic response (HbA1c <53 mmol/mol; odds ratio 2.1, 95% CI 1.23-3.42; P = 0.006). DAPA+SAXA+MET led to greater adjusted mean reductions from baseline in liver fat and visceral and subcutaneous adipose tissue volumes versus GLIM+MET at week 122 (least-squares mean difference from GLIM+MET −4.89%, −0.41 L and −0.44 L, respectively; nominal P values ≤ 0.008). Safety was consistent with that of the monocomponents.
Conclusions:
Overall, glycaemic control, metabolic benefits and efficacy were better maintained with DAPA+SAXA+MET than with GLIM+MET in T2D.

phase III study

type 2 diabetes

liver

DPP-4 inhibitor

dapagliflozin

sulphonylureas

Author

Juan P. Frías

National Research Institute, USA

Jill Maaske

AstraZeneca AB

Lisa Suchower

Kelly Services

Lars Johansson

Antaros Medical AB

Paul Hockings

Chalmers, Electrical Engineering, Signal Processing and Biomedical Engineering

Antaros Medical AB

Nayyar Iqbal

AstraZeneca AB

John P.H. Wilding

University of Liverpool

Diabetes, Obesity and Metabolism

1462-8902 (ISSN) 1463-1326 (eISSN)

Vol. 24 1 61-71

Subject Categories

Endocrinology and Diabetes

Nutrition and Dietetics

DOI

10.1111/dom.14548

PubMed

34514692

More information

Latest update

1/19/2022