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