Vol 73, No 1 (2022)
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Published online: 2022-01-31

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Efficacy and safety of SGLT-2i in overweight/obese, non-diabetic individuals: a meta-analysis of randomized controlled trials

Yetan Shi1, Yuexiu Si2, Rongrong Fu3, Mengting Zhang1, Ke Jiang1, Wei Dai1, Jingyi Shen1, Xiangyuan Li1, Yuan Yuan4
Pubmed: 35119088
Endokrynol Pol 2022;73(1):71-80.


Introduction: Sodium-glucose cotransporter 2 inhibitor (SGLT-2i) has been shown to decrease blood glucose levels in type 2 diabetes mellitus (T2DM) patients and potentially yield additional benefits in weight loss. This meta-analysis aimed to investigate the efficacy and safety of giving SGLT-2i to overweight/obese, non-diabetic individuals.

Material and methods: The search was underpinned by PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Springer to identify English-language papers on randomized controlled trials (RCTs) on the use of SGLT-2i in overweight/obese, nondiabetic individuals published in and before March 2021, to study its effectiveness and safety. Results were evaluated by weighted mean difference (WMD), standardized mean difference (SMD), risk ratio (RR), and 95% confidence interval (CI).

Results: We reviewed 13 papers and compared the SGLT-2i group with the control group (other drugs and placebo) and found that SGLT-2i reduced weight (WMD = –1.33, p = 0.002) and waist circumference (WMD = –1.94, p = 0.03) in overweight/obese, non-diabetic individuals. The use of SGLT-2i is more effective than other interventions in terms of weight loss ≥ 5% (RR = 2.04, p < 0.001), but not in terms of weight loss ≥ 10% (RR = 1.83, p = 0.22). In addition, there were no significant changes in other metabolic parameters, like fasting plasma glucose (FPG), lipids, blood pressure, etc. SGLT-2i increased the risk of infections in urinary tract (RR = 1.91, p = 0.009) and
reproductive system (RR = 4.09, p < 0.001).

Conclusions: SGLT-2i is a promising candidate to reduce weight and waist circumference to a limited extent in overweight/obese, nondiabetic individuals. Generally, it is safe and effective. However, it potentially increased the risk of urogenital infections, which cannot be ignored.

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  1. Hruby A, Hu FB. The Epidemiology of Obesity: A Big Picture. Pharmacoeconomics. 2015; 33(7): 673–689.
  2. Hendryx M, Chojenta C, Byles JE. Obesity Risk Among Young Australian Women: A Prospective Latent Class Analysis. Obesity (Silver Spring). 2020; 28(1): 154–160.
  3. Kabiri M, Sexton Ward A, Ramasamy A, et al. The Societal Value of Broader Access to Antiobesity Medications. Obesity (Silver Spring). 2020; 28(2): 429–436.
  4. Cheng Ji, Gao J, Shuai X, et al. The comprehensive summary of surgical versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomized controlled trials. Oncotarget. 2016; 7(26): 39216–39230.
  5. Tak YJ, Lee SY. Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand? Curr Obes Rep. 2021; 10(1): 14–30.
  6. Tilinca MC, Tiuca RA, Niculas C, et al. Future perspectives in diabesity treatment: Semaglutide, a glucagon-like peptide 1 receptor agonist (Review). Exp Ther Med. 2021; 22(4): 1167.
  7. Cai X, Yang W, Gao X, et al. The Association Between the Dosage of SGLT2 Inhibitor and Weight Reduction in Type 2 Diabetes Patients: A Meta-Analysis. Obesity (Silver Spring). 2018; 26(1): 70–80.
  8. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med. 2009; 151(4): W65–W94.
  9. Bays HE, Kozlovski P, Shao Q, et al. Licogliflozin, a Novel SGLT1 and 2 Inhibitor: Body Weight Effects in a Randomized Trial in Adults with Overweight or Obesity. Obesity (Silver Spring). 2020; 28(5): 870–881.
  10. Bays HE, Weinstein R, Law G, et al. Canagliflozin: effects in overweight and obese subjects without diabetes mellitus. Obesity (Silver Spring). 2014; 22(4): 1042–1049.
  11. Elkind-Hirsch KE, Seidemann E, Harris R. A randomized trial of dapagliflozin and metformin, alone and combined, in overweight women after gestational diabetes mellitus. Am J Obstet Gynecol MFM. 2020; 2(3): 100139.
  12. Færch K, Blond MB, Bruhn L, et al. The effects of dapagliflozin, metformin or exercise on glycaemic variability in overweight or obese individuals with prediabetes (the PRE-D Trial): a multi-arm, randomised, controlled trial. Diabetologia. 2021; 64(1): 42–55.
  13. Hollander P, Bays HE, Rosenstock J, et al. Coadministration of Canagliflozin and Phentermine for Weight Management in Overweight and Obese Individuals Without Diabetes: A Randomized Clinical Trial. Diabetes Care. 2017; 40(5): 632–639.
  14. Javed Z, Papageorgiou M, Deshmukh H, et al. Effects of empagliflozin on metabolic parameters in polycystic ovary syndrome: A randomized controlled study. Clin Endocrinol (Oxf). 2019; 90(6): 805–813.
  15. Napolitano A, Miller S, Murgatroyd PR, et al. Exploring glycosuria as a mechanism for weight and fat mass reduction. A pilot study with remogliflozin etabonate and sergliflozin etabonate in healthy obese subjects. J Clin Transl Endocrinol. 2014; 1(1): e3–e8.
  16. Neeland IJ, de Albuquerque Rocha N, Hughes C, et al. Effects of Empagliflozin Treatment on Glycerol-Derived Hepatic Gluconeogenesis in Adults with Obesity: A Randomized Clinical Trial. Obesity (Silver Spring). 2020; 28(7): 1254–1262.
  17. Newman AA, Grimm NC, Wilburn JR, et al. Influence of Sodium Glucose Cotransporter 2 Inhibition on Physiological Adaptation to Endurance Exercise Training. J Clin Endocrinol Metab. 2019; 104(6): 1953–1966.
  18. Ramírez-Rodríguez AM, González-Ortiz M, Martínez-Abundis E. Effect of Dapagliflozin on Insulin Secretion and Insulin Sensitivity in Patients with Prediabetes. Exp Clin Endocrinol Diabetes. 2020; 128(8): 506–511.
  19. Ryan SPP, Newman AA, Wilburn JR, et al. Sodium Glucose Co-Transporter 2 Inhibition Does Not Favorably Modify the Physiological Responses to Dietary Counselling in Diabetes-Free, Sedentary Overweight and Obese Adult Humans. Nutrients. 2020; 12(2).
  20. Taheri H, Malek M, Ismail-Beigi F, et al. Effect of Empagliflozin on Liver Steatosis and Fibrosis in Patients With Non-Alcoholic Fatty Liver Disease Without Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial. Adv Ther. 2020; 37(11): 4697–4708.
  21. Yokote K, Sano M, Tsumiyama I, et al. Dose-dependent reduction in body weight with LIK066 (licogliflozin) treatment in Japanese patients with obesity. Diabetes Obes Metab. 2020; 22(7): 1102–1110.
  22. Vlacho B, Mundet-Tudurí X, Mata-Cases M, et al. Analysis of the effectiveness of second oral glucose-lowering therapy in routine clinical practice from the mediterranean area: A retrospective cohort study. Diabetes Res Clin Pract. 2021; 171: 108616.
  23. Jabbour SA, Frías JP, Ahmed A, 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 Diabetes Endocrinol. 2016; 4(12): 1004–1016.
  24. Heerspink HJL, Kosiborod M, Inzucchi SE, et al. Renoprotective effects of sodium-glucose cotransporter-2 inhibitors. Kidney Int. 2018; 94(1): 26–39.
  25. Sha S, Polidori D, Heise T, et al. Effect of the sodium glucose co-transporter 2 inhibitor canagliflozin on plasma volume in patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2014; 16(11): 1087–1095.
  26. Rajeev SP, Cuthbertson DJ, Wilding JPH. Energy balance and metabolic changes with sodium-glucose co-transporter 2 inhibition. Diabetes Obes Metab. 2016; 18(2): 125–134.
  27. Ferrannini G, Hach T, Crowe S, et al. Energy Balance After Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care. 2015; 38(9): 1730–1735.
  28. Rebello CJ, Greenway FL. Obesity medications in development. Expert Opin Investig Drugs. 2020; 29(1): 63–71.
  29. Reed JW. Impact of sodium-glucose cotransporter 2 inhibitors on blood pressure. Vasc Health Risk Manag. 2016; 12: 393–405.
  30. Mazidi M, Rezaie P, Gao HK, et al. Effect of Sodium-Glucose Cotransport-2 Inhibitors on Blood Pressure in People With Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of 43 Randomized Control Trials With 22 528 Patients. J Am Heart Assoc. 2017; 6(6).
  31. Verma S, McMurray JJV. SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia. 2018; 61(10): 2108–2117.
  32. Packer M, Butler J, Filippatos G, et al. EMPEROR Trial Committees and Investigators. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet. 2020; 396(10254): 819–829.
  33. Li D, Wu T, Wang T, et al. Effects of sodium glucose cotransporter 2 inhibitors on risk of dyslipidemia among patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. Pharmacoepidemiol Drug Saf. 2020; 29(5): 582–590.
  34. Simental-Mendía M, Sánchez-García A, Rodríguez-Ramírez M, et al. Effect of sodium-glucose co-transporter 2 inhibitors on hepatic parameters: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res. 2021; 163: 105319.
  35. Marjot T, Green CJ, Charlton CA, et al. Sodium-glucose cotransporter 2 inhibition does not reduce hepatic steatosis in overweight, insulin-resistant patients without type 2 diabetes. JGH Open. 2020; 4(3): 433–440.
  36. Geerlings S, Fonseca V, Castro-Diaz D, et al. Genital and urinary tract infections in diabetes: impact of pharmacologically-induced glucosuria. Diabetes Res Clin Pract. 2014; 103(3): 373–381.
  37. Bonnet F, Scheen A. Understanding and overcoming metformin gastrointestinal intolerance. Diabetes Obes Metab. 2017; 19(4): 473–481.