This study assesses the possible side effects of various doses of dapagliflozin. Dapagliflozin is a hypoglycemic agent that inhibits sodium-glucose co-transporter-2 (SGLT2) to remove excess glucose from the body through urination. Hence, dapagliflozin increases the risk for urinary tract infection (UTI) compared with other hypoglycemic agents. Clarifying the side effects of dapagliflozin at different doses and whether these effects are influenced by gender or other factors is significant. Through reviewing the literature on dapagliflozin treatment, we performed a meta-analysis of factors affecting UTI. We then determined the correlation of dapagliflozin treatment with UTI from the pooled data. Each dosing, gender group, or dapagliflozin added to other drugs for diabetes reported a percentage of contracting UTI. Basing on a reference number of pretreatment probability in UTI among patients with diabetes mellitus, we obtained the post-treatment probability in contracting the infection through the meta-analysis. We assessed the risk factors of UTI due to dapagliflozin administration on the basis of the results of odds ratio, regression analysis, and t-test. Considering the add-on-response relation, we recommend that the best add-on hypoglycemic agents to achieve low-risk UTI and control blood glucose are metformin or glimepiride. We also recommend that the best dosage of dapagliflozin is at 1 mg or 2.5 mg.
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XuL., LiY., LangJ., XiaP., ZhaoX., WangL., YuY. and ChenL., Effects of sodium-glucose co-transporter 2 (SGLT2) inhibition on renal function and albuminuria in patients with type 2 diabetes: A systematic review and meta-analysis, Peer J5 (2017), e3405.
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ChrysantS.G., Promising cardiovascular and blood pressure effects of the SGLT2 inhibitors: A new class of antidiabetic drugs, Drugs Today (Barc)53(3) (2017), 191–202.
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JohnssonK.M., PtaszynskaA., SchmitzB., SuggJ., ParikhS.J. and ListJ.F., Urinary tract infections in patients with diabetes treated with dapagliflozin, J Diabetes Complications27(5) (2013), 473–478.
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KanetoH., ObataA., KimuraT., ShimodaM., OkauchiS., ShimoN., MatsuokaT.A. and KakuK., Beneficial effects of sodium-glucose cotransporter 2 inhibitors for preservation of pancreatic β-cell function and reduction of insulin resistance, J Diabetes9(3) (2017), 219–225.
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ZaccardiF., WebbD.R., HtikeZ.Z., YoussefD., KhuntiK. and DaviesM.J., Efficacy and safety of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes mellitus: Systematic review and network meta-analysis, Diabetes Obes Metab18(8) (2016), 783–794.
11.
HuttonB., SalantiG., CaldwellD.M., ChaimaniA., SchmidC.H., CameronC., IoannidisJ.P., StrausS., ThorlundK., JansenJ.P., MulrowC., Catalá-LópezF., GøtzscheP.C.K.DickersinI.BoutronD.G.AltmanD.MoherThe PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: Checklist and explanations, Ann Intern Med162(11) (2015), 777–784.
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MatthaeiS., BoweringK., RohwedderK., SuggJ., ParikhS. and JohnssonE., Study 05 Group: Durability and tolerability of dapagliflozin over 52 weeks as add-on to metformin and sulphonylurea in type 2 diabetes, Diabetes Obes Metab17(11) (2015), 1075–1084.
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RaskinP., Sodium-glucose cotransporter inhibition: Therapeutic potential for the treatment of type 2 diabetes mellitus, Diabetes Metab Res Rev29(5) (2013), 347–356.
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KakuK., InoueS., MatsuokaO., KiyosueA., AzumaH., HayashiN., TokudomeT., LangkildeA.M. and ParikhS., Efficacy and safety of dapagliflozin as a monotherapy for type 2 diabetes mellitus in Japanese patients with inadequate glycaemic control: A phase II multicentre, randomized, double-blind, placebo-controlled trial, Diabetes Obes Metab15(5) (2013), 432–440.
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FerranniniE., RamosS.J., SalsaliA., TangW. and ListJ.F., Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: A randomized, double-blind, placebo-controlled, phase 3 trial, Diabetes Care33(10) (2010), 2217–2224.
16.
BaileyC.J., Morales VillegasE.C.V.Woo W.TangA.PtaszynskaJ.F.ListEfficacy and safety of dapagliflozin monotherapy in people with Type 2 diabetes: A randomized double-blind placebo-controlled 102-week trial, Diabet Med32(4) (2015), 531–541.
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BaileyC.J.J.LGrossD.HennickenN.IqbalT.A.MansfieldJ.F.List, Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: A randomized, double-blind,lacebo-controlled 102-week trial, BMC Med11 (2013), 43.
18.
BaileyC.J., IqbalN., T’joenC. and ListJ.F., Dapagliflozin monotherapy in drug-naïve patients with diabetes: A randomized-controlled trial of low-dose range, Diabetes Obes Metab14(10) (2012), 951–959.
19.
WildingJ.P., NorwoodP., T’joenC., BastienA., ListJ.F. and FiedorekF.T., A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: Applicability of a novel insulin-independent treatment, Diabetes Care32(9) (2009), 1656–1662.
20.
StrojekK., YoonK.H., HrubaV., ElzeM., LangkildeA.M. and ParikhS., Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride: A randomized, 24-week, double-blind, placebo-controlled trial, Diabetes Obes Metab13(10) (2011), 928–938.
21.
RosenstockJ., VicoM., WeiL., SalsaliA. and ListJ.F., Effects of dapagliflozin, an SGLT2 inhibitor, on HbA1c, body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy, Diabetes Care35(7) (2012), 1473–1478.
22.
HenryR.R., MurrayA.V., MarmolejoM.H., HennickenD., PtaszynskaA. and ListJ.F., Dapagliflozin, metformin XR, or both: Initial pharmacotherapy for type 2 diabetes, a randomised controlled trial, Int J Clin Pract66(5) (2012), 446–56.
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