Next Article in Journal
Transscleral Fixation of Black Diaphragm Intraocular Lens in Complete Aniridia and Aphakia Due to Posttraumatic Eye Rupture: A Pilot Study
Next Article in Special Issue
Type 2 Diabetes Is Associated with a Different Pattern of Serum Polyamines: A Case–Control Study from the PREDIMED-Plus Trial
Previous Article in Journal
Pirfenidone, an Anti-Fibrotic Drug, Suppresses the Growth of Human Prostate Cancer Cells by Inducing G1 Cell Cycle Arrest
Previous Article in Special Issue
Plasma Branched-Chain Amino Acids and Risk of Incident Type 2 Diabetes: Results from the PREVEND Prospective Cohort Study
Article Menu

Export Article

Open AccessReview
J. Clin. Med. 2019, 8(1), 45; https://doi.org/10.3390/jcm8010045

Combination Therapy with an SGLT2 Inhibitor as Initial Treatment for Type 2 Diabetes: A Systematic Review and Meta-Analysis

1
Department of Diabetes and Endocrinology, St. Vincent’s Hospital, Sydney, NSW 2010, Australia
2
Department of Clinical Pharmacology and Toxicology, St. Vincent’s Hospital, Sydney, NSW 2010, Australia
3
St. Vincent’s Clinical School, University of NSW, Sydney, NSW 2010, Australia
4
Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
5
School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, Australia
6
Department of Cardiology, St. Vincent’s Hospital, Sydney, NSW 2010, Australia
*
Author to whom correspondence should be addressed.
Received: 14 December 2018 / Revised: 29 December 2018 / Accepted: 29 December 2018 / Published: 4 January 2019
(This article belongs to the Special Issue Type 2 Diabetes: Update on Pathophysiology and Treatment)
Full-Text   |   PDF [1129 KB, uploaded 4 January 2019]   |  
  |   Review Reports

Abstract

Background: Guidelines differ with regard to indications for initial combination pharmacotherapy for type 2 diabetes. Aims: To compare the efficacy and safety of (i) sodium-glucose cotransporter 2 (SGLT2) inhibitor combination therapy in treatment-naïve type 2 diabetes adults; (ii) initial high and low dose SGLT2 inhibitor combination therapy. Methods: PubMed, Embase and Cochrane Library were searched for randomised controlled trials (RCTs) of initial SGLT2 combination therapy. Mean difference (MD) for changes from baseline (HbA1c, weight, blood pressure) after 24–26 weeks of treatment and relative risks (RR, safety) were calculated using a random-effects model. Risk of bias and quality of evidence was assessed. Results: In 4 RCTs (n = 3749) there was moderate quality evidence that SGLT2 inhibitor/metformin combination therapy resulted in a greater reduction in HbA1c (MD (95% CI); −0.55% (−0.67, −0.43)) and weight (−2.00 kg (−2.34, −1.66)) compared with metformin monotherapy, and a greater reduction in HbA1c (−0.59% (−0.72, −0.46)) and weight (−0.57 kg (−0.89, −0.25)) compared with SGLT2 inhibitor monotherapy. The high dose SGLT2 inhibitor/metformin combination resulted in a similar HbA1c but greater weight reduction; −0.47 kg (−0.88, −0.06) than the low dose combination therapy. The RR of genital infection with combination therapy was 2.22 (95% CI 1.33, 3.72) and 0.69 (95% CI 0.50, 0.96) compared with metformin and SGLT2 inhibitor monotherapy, respectively. The RR of diarrhoea was 2.23 (95% CI 1.46, 3.40) with combination therapy compared with SGLT2 inhibitor monotherapy. Conclusions: Initial SGLT2 inhibitor/metformin combination therapy has glycaemic and weight benefits compared with either agent alone and appears relatively safe. High dose SGLT2 inhibitor/metformin combination therapy appears to have modest weight, but no glycaemic benefits compared with the low dose combination therapy. View Full-Text
Keywords: type 2 diabetes; pharmacotherapy; SGLT2 inhibitors; metformin; DPP-4 inhibitors; clinical pharmacology type 2 diabetes; pharmacotherapy; SGLT2 inhibitors; metformin; DPP-4 inhibitors; clinical pharmacology
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Milder, T.Y.; Stocker, S.L.; Abdel Shaheed, C.; McGrath-Cadell, L.; Samocha-Bonet, D.; Greenfield, J.R.; Day, R.O. Combination Therapy with an SGLT2 Inhibitor as Initial Treatment for Type 2 Diabetes: A Systematic Review and Meta-Analysis. J. Clin. Med. 2019, 8, 45.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
J. Clin. Med. EISSN 2077-0383 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top