Volume 22, Issue 7 p. 1035-1046
REVIEW ARTICLE

Efficacy and tolerability of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: A systematic review and network meta-analysis

Humaira Hussein MSc

Corresponding Author

Humaira Hussein MSc

Department of Health Sciences, University of Leicester, Leicester, UK

Diabetes Research Centre, University of Leicester, Leicester, UK

Correspondence

Humaira Hussein, Department of Health Sciences, University of Leicester, Leicester Diabetes Centre, Leicester General Hospital, Leicester, Leicestershire LE5 4PW, UK.

Email: [email protected]

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Francesco Zaccardi PhD

Francesco Zaccardi PhD

Diabetes Research Centre, University of Leicester, Leicester, UK

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Kamlesh Khunti PhD

Kamlesh Khunti PhD

Diabetes Research Centre, University of Leicester, Leicester, UK

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Melanie J. Davies MD

Melanie J. Davies MD

Diabetes Research Centre, University of Leicester, Leicester, UK

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Emily Patsko MSc

Emily Patsko MSc

Diabetes Research Centre, University of Leicester, Leicester, UK

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Nafeesa N. Dhalwani PhD

Nafeesa N. Dhalwani PhD

Real World Evidence, London, UK

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David E. Kloecker MPhil

David E. Kloecker MPhil

Diabetes Research Centre, University of Leicester, Leicester, UK

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Ekaterini Ioannidou MSc

Ekaterini Ioannidou MSc

Diabetes Research Centre, University of Leicester, Leicester, UK

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Laura J. Gray PhD

Laura J. Gray PhD

Department of Health Sciences, University of Leicester, Leicester, UK

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First published: 19 February 2020
Citations: 44
Peer Review The peer review history for this article is available at https://publons.com/publon/10.1111/dom.14008.

Abstract

Aim

To compare the efficacy and tolerability of sodium-glucose co-transporter 2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adults with type 2 diabetes.

Materials and methods

Electronic databases were searched from inception to 24 April 2019 for randomized controlled trials reporting change in glycated haemoglobin (HbA1c) at approximately 24 and/or 52 weeks for SGLT-2is and/or GLP-1RAs (classified as short- and long-acting). Bayesian network meta-analyses were conducted to compare within and between SGLT-2i and GLP-1RA classes for cardiometabolic efficacy and adverse events (PROSPERO registration number: CRD42018091306).

Results

Sixty-four trials (53 trials of 24 weeks; seven trials of 52 weeks; four trials of both 24 and 52 weeks), comprising 31 384 participants were identified. Compared with placebo, all treatments improved HbA1c. Long-acting GLP-1RAs reduced HbA1c compared with short-acting GLP-1RAs and SGLT-2is, with semaglutide showing greater reduction compared with placebo [24 weeks: −1.49% (95% credible interval: −1.76, −1.22); 52 weeks: −1.38% (−2.05, −0.71)] and all other treatments. Long-acting GLP-1RAs showed benefits in body weight and waist circumference reduction, while SGLT-2is reduced blood pressure. SGLT-2is showed increased risk of genital infection in comparison with long-acting GLP-1RAs [odds ratio (95% credible interval): 5.26 (1.45, 25.00)], while GLP-1RAs showed increased risk of diarrhoea in comparison with SGLT-2is [short-acting GLP-1RAs: 1.65 (1.09, 2.49); long-acting GLP-1RAs: 2.23 (1.51, 3.28)]. No other differences were found between SGLT-2is and GLP-1RAs in adverse events.

Conclusion

Long-acting GLP-1RAs showed superiority in reducing HbA1c levels, body weight and waist circumference. SGLT-2is showed reductions in blood pressure levels. This review provides essential evidence to guide treatment recommendations in the management of type 2 diabetes.

CONFLICT OF INTEREST

K.K. has acted as a consultant and speaker for Novartis, Novo Nordisk, Sanofi-Aventis, Lilly and Merck Sharp & Dohme. K.K. has also received grants in support of investigator and investigator-initiated trials from Novartis, Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Pfizer and Boehringer Ingelheim and has served on advisory boards for Novo Nordisk, Sanofi-Aventis, Lilly and Merck Sharp & Dohme. M.D. has acted as consultant, speaker and advisory board member for Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca and Janssen. She has acted as a speaker for Mitsubishi Tanabe Pharma Corporation and has received grants in support of investigator and investigator-initiated trials from Novo Nordisk, Sanofi-Aventis and Lilly. S.S. has acted as consultant, speaker and advisory board member for Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, Amgen, AstraZeneca and Janssen, NAPP and Novartis. F.Z. has acted as a speaker for NAPP.