Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2020 Jul;22(7):1094-1101.
doi: 10.1111/dom.14004. Epub 2020 Mar 9.

Dapagliflozin plus saxagliptin add-on to metformin reduces liver fat and adipose tissue volume in patients with type 2 diabetes

Lars Johansson  1 , Paul D Hockings  1 , Eva Johnsson  2 , Nalina Dronamraju  3 , Jill Maaske  3 , Ricardo Garcia-Sanchez  3 , John P H Wilding  4
Affiliations
Randomized Controlled Trial

Dapagliflozin plus saxagliptin add-on to metformin reduces liver fat and adipose tissue volume in patients with type 2 diabetes

Lars Johansson et al. Diabetes Obes Metab. 2020 Jul.

Abstract

Aim: To assess the effects of dapagliflozin plus saxagliptin plus metformin versus glimepiride plus metformin on liver fat (proton density fat fraction) and visceral and subcutaneous adipose tissue volumes over 52 weeks of treatment.

Materials and methods: This was a magnetic resonance imaging substudy of a 52-week, multicentre, randomized, double-blind, parallel-group trial that evaluated the efficacy and safety of dapagliflozin 10 mg/day plus saxagliptin 5 mg/day versus titrated glimepiride 1-6 mg (1, 2, 3, 4 or 6 mg) in 82 patients with type 2 diabetes (HbA1c 7.5%-10.5%) on metformin ≥1500 mg/day background. Analyses were exploratory and not controlled for multiplicity; P-values are nominal.

Results: Magnetic resonance imaging was performed on 59 patients; liver fat and adipose tissue volumes were analysed for 59 and 57 patients, respectively. There was a significant >30% reduction from baseline in liver fat (P = 0.007) and >10% reduction in adipose tissue volumes (P < 0.01) with dapagliflozin plus saxagliptin plus metformin at week 52 versus glimepiride plus metformin. In the full-study population, dapagliflozin plus saxagliptin plus metformin decreased body weight and serum alanine aminotransferase and aspartate aminotransferase levels over 52 weeks.

Conclusions: Dapagliflozin plus saxagliptin significantly decreased liver fat and adipose tissue volume versus glimepiride, and reduced serum liver enzyme levels, indicating a favourable metabolic profile of dapagliflozin plus saxagliptin in patients with type 2 diabetes on metformin therapy.

Keywords: dapagliflozin; ectopic fat; fixed-dose combination; glimepiride; liver fat; magnetic resonance imaging-estimated proton density fat fraction; metformin; nonalcoholic fatty liver disease; saxagliptin; sodium-glucose co-transporter-2 inhibitors.

PubMed Disclaimer

Conflict of interest statement

ND, JM and EJ are employees of AstraZeneca. RG‐S was an employee of AstraZeneca at the time the work was conducted. PDH and LJ are employees of Antaros Medical AB, which received payment from AstraZeneca for conducting the study. LJ is a shareholder in Antaros Medical AB. JPHW, outside the submitted work, has grants, personal fees and consultancy fees (paid to his institution) from AstraZeneca, Novo Nordisk and Takeda; personal fees and consultancy fees (paid to his institution) from Boehringer Ingelheim, Janssen, Lilly, Mundipharma, Napp and Sanofi; and consultancy fees (paid to his institution) from Wilmington Healthcare.

Figures

Figure 1
Figure 1
Study design (NCT02419612). DAPA, dapagliflozin; GLIM, glimepiride; IR, instant release; MET, metformin; SAXA, saxagliptin; XR, extended release
Figure 2
Figure 2
Representation of liver magnetic resonance imaging‐estimated proton density fat fraction (MRI‐PDFF) pre‐ and post‐treatment. (A) Pre‐ and post‐treatment MRI‐PDFF for dapagliflozin plus saxagliptin plus metformin and (B) pre‐ and post‐treatment MRI‐PDFF for glimepiride plus metformin
Figure 3
Figure 3
Adjusted mean change from baseline in total body weight during the 52‐week, double‐blind treatment period†. Body weight assessments collected after initiation of rescue treatment or collected more than 8 days after the last dose in the short‐term, double‐blind treatment period were excluded from the analysis. †Patients from the randomized patient dataset with nonmissing baseline assessment at week 52 were included in this analysis. Baseline is defined as patients in the randomized patient dataset with nonmissing baseline assessment and at least one postbaseline assessment. DAPA, dapagliflozin; GLIM, glimepiride; MET, metformin; SAXA, saxagliptin
See this image and copyright information in PMC

References

    1. Horton ES, Silberman C, Davis KL, Berria R. Weight loss, glycemic control, and changes in cardiovascular biomarkers in patients with type 2 diabetes receiving incretin therapies or insulin in a large cohort database. Diabetes Care. 2010;33:1759‐1765. - PMC - PubMed
    1. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67:328‐357. - PubMed
    1. Ahmed A, Wong RJ, Harrison SA. Nonalcoholic fatty liver disease review: diagnosis, treatment, and outcomes. Clin Gastroenterol Hepatol. 2015;13:2062‐2070. - PubMed
    1. Kwok R, Choi KC, Wong GL, et al. Screening diabetic patients for non‐alcoholic fatty liver disease with controlled attenuation parameter and liver stiffness measurements: a prospective cohort study. Gut. 2016;65:1359‐1368. - PubMed
    1. Leite NC, Salles GF, Araujo AL, Villela‐Nogueira CA, Cardoso CR. Prevalence and associated factors of non‐alcoholic fatty liver disease in patients with type‐2 diabetes mellitus. Liver Int. 2009;29:113‐119. - PubMed

Publication types

Grants and funding