open access
Short- and medium-term efficacy of sodium glucose cotransporter 2 (SGLT-2) inhibitors for the treatment of type 1 diabetes: systematic review and meta-analysis
Affiliations- Department of Clinical Medicine, The First Clinical Medical College, Nanchang University, Nanchang, China
- Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China
open access
Abstract
Introduction: Sodium glucose cotransporter 2 (SGLT2) inhibitors are insulin-independent and glucose-dependent anti-hyperglycaemic drugs that have shown potential as an adjuvant therapy to insulin for the treatment of type 1 diabetes mellitus (T1DM). The purpose of this meta-analysis is to systematically collect available data from randomised trials to determine SGLT-2 inhibitor efficacy in terms of glycaemic control, body mass index, and renal protection when compared with placebo. Material and methods: Cochrane Library, MEDLINE, and EMBASE databases were searched for randomised controlled trials and metaanalyses (without language restrictions) conducted from January 2010 to September 2019. Results: Seventeen randomised controlled trials with 7325 participants were included. Sodium glucose cotransporter 2 therapy significantly reduced the level of glycated haemoglobin (HbA1c) (by 0.37%), body weight (by 2.88 kg), and estimated glomerular filtration (eGFR) (by 0.67 mL/min/1.73 m²) when compared with placebo (all outcomes, p < 0.00001). Subgroup analysis by HbA1c levels showed significant differences between six and 12 months of treatment (p < 0.1). The magnitude of the HbA1c lowering effect waned with longer duration of treatment after six months (up to 12 months). Subgroup analysis by body weight showed significant differences between 1 and 3–4 months of treatment (p < 0.1). Weight loss plateaued after 3–4 months of treatment; subsequently, the weight remained relatively stable until 12 months. Subgroup analysis by eGFR showed significant differences between six and 12 months of treatment (p < 0.1). The magnitude of the eGFR lowering effect increased with longer duration of treatment after six months (up to 12 months). Conclusions: Sodium glucose cotransporter 2 inhibitors show significant therapeutic effects when compared with placebo. Although changes in HbA1c, body weight, and eGFR vary during treatment, the therapeutic effects of SGLT-2 inhibitors measured by these three outcomes can last up to 12 months. More long-term, randomised trials and extended studies are needed to determine the long-term effects of SGLT2 inhibitors as adjuvant therapy for T1DM patients.
Abstract
Introduction: Sodium glucose cotransporter 2 (SGLT2) inhibitors are insulin-independent and glucose-dependent anti-hyperglycaemic drugs that have shown potential as an adjuvant therapy to insulin for the treatment of type 1 diabetes mellitus (T1DM). The purpose of this meta-analysis is to systematically collect available data from randomised trials to determine SGLT-2 inhibitor efficacy in terms of glycaemic control, body mass index, and renal protection when compared with placebo. Material and methods: Cochrane Library, MEDLINE, and EMBASE databases were searched for randomised controlled trials and metaanalyses (without language restrictions) conducted from January 2010 to September 2019. Results: Seventeen randomised controlled trials with 7325 participants were included. Sodium glucose cotransporter 2 therapy significantly reduced the level of glycated haemoglobin (HbA1c) (by 0.37%), body weight (by 2.88 kg), and estimated glomerular filtration (eGFR) (by 0.67 mL/min/1.73 m²) when compared with placebo (all outcomes, p < 0.00001). Subgroup analysis by HbA1c levels showed significant differences between six and 12 months of treatment (p < 0.1). The magnitude of the HbA1c lowering effect waned with longer duration of treatment after six months (up to 12 months). Subgroup analysis by body weight showed significant differences between 1 and 3–4 months of treatment (p < 0.1). Weight loss plateaued after 3–4 months of treatment; subsequently, the weight remained relatively stable until 12 months. Subgroup analysis by eGFR showed significant differences between six and 12 months of treatment (p < 0.1). The magnitude of the eGFR lowering effect increased with longer duration of treatment after six months (up to 12 months). Conclusions: Sodium glucose cotransporter 2 inhibitors show significant therapeutic effects when compared with placebo. Although changes in HbA1c, body weight, and eGFR vary during treatment, the therapeutic effects of SGLT-2 inhibitors measured by these three outcomes can last up to 12 months. More long-term, randomised trials and extended studies are needed to determine the long-term effects of SGLT2 inhibitors as adjuvant therapy for T1DM patients.
Keywords
sodium-glucose co-transporter 2; therapeutic effects; type 1 diabetes; meta-analysis; systematic review
Supp./Additional Files (1)
About this articleTitle
Short- and medium-term efficacy of sodium glucose cotransporter 2 (SGLT-2) inhibitors for the treatment of type 1 diabetes: systematic review and meta-analysis
Journal
Issue
Article type
Review paper
Pages
325-333
Published online
2020-06-01
Page views
1683
Article views/downloads
1377
DOI
Pubmed
Bibliographic record
Endokrynol Pol 2020;71(4):325-333.
Keywords
sodium-glucose co-transporter 2
therapeutic effects
type 1 diabetes
meta-analysis
systematic review
Authors
Yuxin Huang
Zeju Jiang
Yiping Wei
References (43)- Chiang J, Kirkman M, Laffel L, et al. Type 1 Diabetes Through the Life Span: A Position Statement of the American Diabetes Association. Diab Care. 2014; 37(7): 2034–2054.
- Health Canada. 2014. Summary of Health Canada’sAssessment of a Health Claim about GroundWhole Flaxseed and Blood Cholesterol Lowering. http://www.hc-sc.gc.ca/fn-an/alt_formats/pdf/label-etiquet/claims-reclam/assess-evalu/flaxseedgraines-de-lin-eng. (May 11 2014).
- Orchard T, Nathan D, Zinman B, et al. Association Between 7 Years of Intensive Treatment of Type 1 Diabetes and Long-term Mortality. JAMA. 2015; 313(1): 45–53.
- Frandsen C, Dejgaard T, Madsbad S. Non-insulin drugs to treat hyperglycaemia in type 1 diabetes mellitus. Lancet Diabetes Endocrinol. 2016; 4(9): 766–780.
- Purnell J, Hokanson J, Marcovina S, et al. Effect of Excessive Weight Gain With Intensive Therapy of Type 1 Diabetes on Lipid Levels and Blood Pressure. JAMA. 1998; 280(2): 140–146.
- Vasilakou D, Karagiannis T, Athanasiadou E, et al. Sodium–Glucose Cotransporter 2 Inhibitors for Type 2 Diabetes. Ann Int Med. 2013; 159(4): 262–274.
- Yang XP, Lai D, Zhong XY, et al. Efficacy and safety of canagliflozin in subjects with type 2 diabetes: systematic review and meta-analysis. Eur J Clin Pharmacol. 2014; 70(10): 1149–1158.
- Baker W, Smyth L, Riche D, et al. Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: A systematic review and meta-analysis. J Am Soc Hypertens. 2014; 8(4): 262–275.e9.
- Monami M, Nardini C, Mannucci E. Efficacy and safety of sodium glucose co-transport-2 inhibitors in type 2 diabetes: a meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2013; 16(5): 457–466.
- Liakos A, Karagiannis T, Athanasiadou E, et al. Efficacy and safety of empagliflozin for type 2 diabetes: a systematic review and meta-analysis. Diabetes Obes Metab. 2014; 16(10): 984–993.
- Chen J, Fan F, Wang JY, et al. The efficacy and safety of SGLT2 inhibitors for adjunctive treatment of type 1 diabetes: a systematic review and meta-analysis. Scientific Reports. 2017; 7(1): 44128.
- Li K, Xu G. Safety and efficacy of sodium glucose co‐transporter 2 inhibitors combined with insulin in adults with type 1 diabetes: A meta‐analysis of randomized controlled trials. J Diabetes. 2019; 11(8): 645–655.
- Masri DEl, Ghosh S, Jaber L. Safety and efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in type 1 diabetes: A systematic review and meta-analysis. Diabetes Res Clin Pract. 2018; 137: 83–92.
- Yamada T, Shojima N, Noma H, et al. Sodium‐glucose co‐transporter‐2 inhibitors as add‐on therapy to insulin for type 1 diabetes mellitus: Systematic review and meta‐analysis of randomized controlled trials. Diabetes Obes Metab. 2018; 20(7): 1755–1761.
- Shamseer L, Moher D, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015; 350: g7647.
- Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions, version 5.2.0. , updated March 2011. Cochrane Collaboration, John Wiley & Sons Ltd 2011: July.
- Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009; 339: b2700.
- Higgins J. Measuring inconsistency in meta-analyses. BMJ. 2003; 327(7414): 557–560.
- Egger M, Smith GD, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997; 315(7109): 629–634.
- Baker C, Wason S, Banks P, et al. Dose‐dependent glycometabolic effects of sotagliflozin on type 1 diabetes over 12 weeks: The inTandem4 trial. Diabetes Obes Metab. 2019; 21(11): 2440–2449.
- Bode B, Banks P, Sawhney S, et al. Efficacy and safety of sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, as adjunct to insulin in young adults with poorly controlled type 1 diabetes (JDRF Study). Diabetologia. 2017; 60: S87–S88.
- Buse J, Garg S, Rosenstock J, et al. Sotagliflozin in Combination With Optimized Insulin Therapy in Adults With Type 1 Diabetes: The North American inTandem1 Study. Diab Care. 2018; 41(9): 1970–1980.
- Dandona P, Mathieu C, Phillip M, et al. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diab Endocrinol. 2017; 5(11): 864–876.
- Dandona P, Mathieu C, Phillip M, et al. Efficacy and Safety of Dapagliflozin in Patients With Inadequately Controlled Type 1 Diabetes: The DEPICT-1 52-Week Study. Diabetes Care. 2018; 41(12): 2552–2559.
- Danne T, Cariou B, Banks P, et al. HbA1cand Hypoglycemia Reductions at 24 and 52 Weeks With Sotagliflozin in Combination With Insulin in Adults With Type 1 Diabetes: The European inTandem2 Study. Diab Care. 2018; 41(9): 1981–1990.
- Famulla S, Pieber T, Eilbracht J, et al. Glucose Exposure and Variability with Empagliflozin as Adjunct to Insulin in Patients with Type 1 Diabetes: Continuous Glucose Monitoring Data from a 4-Week, Randomized, Placebo-Controlled Trial (EASE-1). Diab Technol Ther. 2017; 19(1): 49–60.
- Garg S, Henry R, Banks P, et al. Effects of Sotagliflozin Added to Insulin in Patients with Type 1 Diabetes. N Engl J Med. 2017; 377(24): 2337–2348.
- Henry R, Dandona P, Pettus J, et al. Dapagliflozin in patients with type 1 diabetes: Apost hoc analysis of the effect of insulin dose adjustments on 24-hour continuously monitored mean glucose and fasting β-hydroxybutyrate levels in a phase IIa pilot study. Diabetes Obes Metab. 2017; 19(6): 814–821.
- Henry R, Thakkar P, Tong C, et al. Efficacy and Safety of Canagliflozin, a Sodium–Glucose Cotransporter 2 Inhibitor, as Add-on to Insulin in Patients With Type 1 Diabetes. Diabetes Care. 2015; 38(12): 2258–2265.
- Kaku K, Isaka H, Toyoshima J, et al. Clinical pharmacology study of ipragliflozin in Japanese patients with type 1 diabetes mellitus: A phase 2, randomized, placebo‐controlled trial. Diabetes Obes Metab. 2019; 21(6): 1445–1454.
- Kaku K, Isaka H, Sakatani T, et al. Efficacy and safety of ipragliflozin add‐on therapy to insulin in Japanese patients with type 1 diabetes mellitus: A randomized, double‐blind, phase 3 trial. Diabetes Obes Metab. 2019; 21(10): 2284–2293.
- Kuhadiya N, Ghanim H, Mehta A, et al. Dapagliflozin as Additional Treatment to Liraglutide and Insulin in Patients With Type 1 Diabetes. J Clin Endocrinol Metab. 2016; 101(9): 3506–3515.
- Mathieu C, Dandona P, Gillard P, et al. Efficacy and Safety of Dapagliflozin in Patients With Inadequately Controlled Type 1 Diabetes (the DEPICT-2 Study): 24-Week Results From a Randomized Controlled Trial. Diabetes Care. 2018; 41(9): 1938–1946.
- Rosenstock J, Marquard J, Laffel L, et al. Empagliflozin as Adjunctive to Insulin Therapy in Type 1 Diabetes: The EASE Trials. Diabetes Care. 2018; 41(12): 2560–2569.
- Sands A, Zambrowicz B, Rosenstock J, et al. Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes. Diabetes Care. 2015; 38(7): 1181–1188.
- Shimada A, Hanafusa T, Yasui A, et al. Empagliflozin as adjunct to insulin in Japanese participants with type 1 diabetes: Results of a 4-week, double-blind, randomized, placebo-controlled phase 2 trial. Diabetes Obes Metab. 2018; 20(9): 2190–2199.
- Garber AJ. Treat-to-target trials: uses, interpretation and review of concepts. Diabetes Obes Metab. 2013; 16(3): 193–205.
- Danne T, Nimri R, Battelino T, et al. International Consensus on Use of Continuous Glucose Monitoring. Diabetes Care. 2017; 40(12): 1631–1640.
- McKnight JA, Wild SH, Lamb M, et al. Glycaemic control of Type 1 diabetes in clinical practice early in the 21st century: an international comparison. Diabet Med. 2015; 32(8): 1036–1050.
- Miller K, Foster N, Beck R, et al. Current State of Type 1 Diabetes Treatment in the U.S.: Updated Data From the T1D Exchange Clinic Registry. Diabetes Care. 2015; 38(6): 971–978.
- Weinstock R, Schütz-Fuhrmann I, Connor C, et al. Type 1 diabetes in older adults: Comparing treatments and chronic complications in the United States T1D Exchange and the German/Austrian DPV registries. Diabetes Res Clin Pract. 2016; 122: 28–37.
- Wing RR, Lang W, Wadden TA, et al. Benefits of Modest Weight Loss in Improving Cardiovascular Risk Factors in Overweight and Obese Individuals With Type 2 Diabetes. Diabetes Care. 2011; 34(7): 1481–1486.
- Van Ga, Wauters MA, De Le. The beneficial effects of modest weight loss on cardiovascular risk factors. Int J Obes Relat Metab Disord . 1997; 21(Suppl 1): S5–S9.
