Efficacy and tolerability of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: A systematic review and network meta-analysis
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).
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.
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.
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Appendix S1: Supporting information.
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- 1 American Diabetes Association. Pharmacologic approaches to glycemic treatment: Standards of medical care in Diabetes - 2018. Diabetes Care. 2018; 41(suppl 1): S73-S85.
- 2 National Institute for Health and Care Excellence. Type 2 Diabetes in Adults: Management. London: National Institute for Health and Care Excellence; 2015 https://www.nice.org.uk/guidance/ng28. Accessed August 7, 2019.
- 3, , , et al. Management of hyperglycemia in type 2 diabetes, 2018: a consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018; 41(12):dci180033.
- 4, , , , , . Cardiovascular efficacy and safety of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: a systematic review and network meta-analysis. Diabet Med. 2019; 36(4): 444-452.
- 5, , , et al. Association between use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase 4 inhibitors with all-cause mortality in patients with type 2 diabetes: a systematic review and meta-analysis. JAMA. 2018; 319(15): 1580-1591.
- 6. Sodium-glucose co-transporters and their inhibition: clinical physiology. Cell Metab. 2017; 26(1): 27-38.
- 7, . Sodium-glucose co-transporter inhibitors: mechanisms of action. Aust Prescr. 2013; 37(1): 14-16.
- 8, , , , , . Pharmacology for Pharmacy and the Health Sciences: a Patient-Centred Approach. Oxford: Oxford University Press; 2017.
- 9, , , . GLP-1RAs in type 2 diabetes: mechanisms that underlie cardiovascular effects and overview of cardiovascular outcome data. Cardiovasc Diabetol. 2018; 17(1): 157.
- 10, , , , , . Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: a systematic review and mixed-treatment comparison analysis. Diabetes Obes Metab. 2017; 19(4): 524-536.
- 11, , , et al. Benefits and harms of sodium-glucose co-transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and meta-analysis. PLoS One. 2016; 11(11):e0166125.
- 12, , , , . Benefits and harms of once-weekly glucagon-like peptide-1 receptor agonist treatments: a systematic review and network meta-analysis. Ann Intern Med. 2016; 164(2): 102-113.
- 13, , , , , . Efficacy and safety of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes mellitus: systematic review and network meta-analysis. Diabetes Obes Metab. 2016; 18(8): 783-794.
- 14, , , et al. Exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy (DURATION-8): a 28 week, multicentre, double-blind, phase 3, randomised controlled trial. Lancet. 2016; 4(12): 1004-1016. http://cochranelibrary-wiley.com/o/cochrane/clcentral/articles/336/CN-01288336/frame.html https://www.thelancet.com/journals/landia/article/PIIS2213-8587(16)30267-4/fulltext.
- 15, , , et al. Safety and efficacy of exenatide once weekly plus dapagliflozin once daily versus exenatide or dapagliflozin alone in patients with type 2 diabetes inadequately controlled with metformin monotherapy: 52-week results of the DURATION-8 randomized controlled trial. Diabetes Care. 2018; 41(10): 2136-2146.
- 16, . Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration; 2011 http://handbook.cochrane.org. Accessed May 23, 2018.
- 17, , , , , . Efficacy and safety of sodium-glucose cotransporter 2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with type 2 diabetes: a systematic review and network meta-analysis study protocol. BMJ Open. 2018; 8(11):e023206.
- 18, , , et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015; 162(11): 777-784.
- 19, , . et al; the PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015; 349:g7647.
- 20 National Institute for Health Care Excellence. British National Formulary 2019. London: National Institute for Health Care Excellence. https://bnf.nice.org.uk/. Accessed August 22, 2019.
- 21 Food Drug Administration. Food Drug Administration, United States. https://www.fda.gov/. Accessed August 22, 2019.
- 22, , , et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011; 343:d5928.
- 23, , , , . Graphical tools for network meta-analysis in STATA. PLoS One. 2013; 8(10):e76654.
- 24, , , . Evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network meta- analysis of randomized controlled trials. Med Decis Making. 2013; 33(5): 607-617.
- 25, , . Network meta-analysis: development of a three-level hierarchical modeling approach incorporating dose-related constraints. Value Health. 2015; 18(1): 116-126.
- 26, , , et al. A GRADE working group approach for rating the quality of treatment effect estimates from network meta-analysis. BMJ. 2014; 349:g5630.
- 27, , , , . A design-by-treatment interaction model for network meta-analysis with random inconsistency effects. Stat Med. 2014; 33(21): 3639-3654.
- 28. Pharmacologic management of type 2 diabetes mellitus: available therapies. Am J Cardiol. 2017; 120(1): S4-S16.
- 29, , , . Genital infections with sodium glucose cotransporter-2 inhibitors: occurrence and management in patients with type 2 diabetes mellitus. Indian J Endocrinol Metab. 2018; 22(6): 837-842.
- 30, , , et al. Association of HbA 1c levels with vascular complications and death in patients with type 2 diabetes: evidence of glycaemic thresholds. Diabetologia. 2012; 55(3): 636-643.
- 31FDA approves first oral GLP-1 treatment for type 2 diabetes; 2019. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-glp-1-treatment-type-2-diabetes. Accessed October 8, 2019.
- 32, , , et al. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial. Lancet. 2019; 394: 39-50.
- 33, , , et al. Efficacy and safety of once-weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes (SUSTAIN 8): a double-blind, phase 3b, randomised controlled trial. Lancet. 2019; 7(11): 834-844.
- 34, , , , , . Effect of oral semaglutide compared with placebo and subcutaneous semaglutide on glycemic control in patients with type 2 diabetes: a randomized clinical trial. JAMA. 2017; 318(15): 1460-1470.
- 35, , , . Network meta-analysis: a technique to gather evidence from direct and indirect comparisons. Pharm Pract. 2017; 15(1): 943.
- 36, , , . Searching for indirect evidence and extending the network of studies for network meta-analysis: case study in venous thromboembolic events prevention following elective total knee replacement surgery. Value Health. 2014; 17(4): 416-423.