A review of clinical efficacy and safety of canagliflozin 300 mg in the management of patients with type 2 diabetes mellitus

K M Prasanna Kumar, Sujoy Ghosh, William Canovatchel, Nishant Garodia, Sujith Rajashekar, K M Prasanna Kumar, Sujoy Ghosh, William Canovatchel, Nishant Garodia, Sujith Rajashekar

Abstract

Currently available antihyperglycemic agents, despite being effective, provide inadequate glycemic control and/or are associated with side effects or nonadherence. Canagliflozin, a widely used orally active inhibitor of sodium-glucose cotransporter 2 (SGLT2), is a new addition to the therapeutic armamentarium of glucose-lowering drugs. This review summarizes findings from different clinical and observational studies of canagliflozin 300 mg in patients with type 2 diabetes mellitus (T2DM). By inhibiting SGLT2, canagliflozin reduces reabsorption of filtered glucose, thereby increasing urinary glucose excretion in patients with T2DM. Canagliflozin 300 mg has been shown to be effective in lowering glycated hemoglobin, fasting plasma glucose, and postprandial glucose in patients with T2DM. Canagliflozin 300 mg also demonstrated significant reductions in body weight and blood pressure and has a low risk of causing hypoglycemia, when not used in conjunction with insulin and insulin secretagogues. Canagliflozin 300 mg was generally well tolerated in clinical studies. The most frequently reported adverse events include genital mycotic infections, urinary tract infections, osmotic diuresis, and volume depletion-related events.

Keywords: Canagliflozin; glycated hemoglobin; hypoglycemic agents; pleiotropic benefits; sodium-glucose cotransporter 2 inhibitor; type 2 diabetes mellitus.

Conflict of interest statement

Dr. K. M. Prasanna Kumar and Dr. Sujoy Ghosh have received honoraria from Johnson and Johnson Pvt. Ltd., India. Dr. William Canovatchel is an employee of Janssen Research and Development, LLC. Dr. Nishant Garodia and Dr. Sujith Rajashekar are employees of Johnson and Johnson Pvt. Ltd, India. We have no other relevant affiliations or financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1
Figure 1
Target organs of antihyperglycemic agents. AHA: Antihyperglycemic agent; DPP-4: Dipeptidyl peptidase-4; GLP-1: Glucagon-like peptide-1; SGLT2i: Sodium-glucose cotransporter 2 inhibitor
Figure 2
Figure 2
Mechanism of action of sodium-glucose cotransporter 2 inhibitors. T2DM: Type 2 diabetes mellitus; SGLT: Sodium-glucose cotransporter. This figure has been taken from Kalra et al.
Figure 3
Figure 3
Mean change in glycated hemoglobin, fasting plasma glucose, and postprandial glucose in clinical studies with canagliflozin monotherapy versus placebo. HbA1c: Glycated hemoglobin; FPG: Fasting plasma glucose; PPG: Postprandial glucose
Figure 4
Figure 4
Mean change in glycated hemoglobin, fasting plasma glucose, and postprandial glucose in clinical studies with canagliflozin as add-on therapy versus placebo/active comparators, sitagliptin, glimepiride, and insulin. HbA1c: Glycated hemoglobin; CANA: Canagliflozin; FPG: Fasting plasma glucose; GLIM: Glimepiride; MET: Metformin; OHAs: Oral hypoglycemic agents; PPG: Postprandial glucose; SITA: Sitagliptin; SU: Sulfonylurea
Figure 5
Figure 5
Proportion of patients achieving glycated hemoglobin

Figure 6

Percent change in body weight…

Figure 6

Percent change in body weight in clinical studies with canagliflozin as monotherapy or…

Figure 6
Percent change in body weight in clinical studies with canagliflozin as monotherapy or add-on therapy versus placebo/active comparators, sitagliptin, glimepiride and insulin. CANA: Canagliflozin; GLIM: Glimepiride; LS: Least squares; MET: Metformin; OHAs: Oral hypoglycemic agents; SITA: Sitagliptin; SU: Sulfonylurea

Figure 7

Change in systolic blood pressure…

Figure 7

Change in systolic blood pressure in clinical studies with canagliflozin as monotherapy or…

Figure 7
Change in systolic blood pressure in clinical studies with canagliflozin as monotherapy or add-on therapy versus placebo/active comparators, sitagliptin, glimepiride and insulin. CANA: Canagliflozin; GLIM: Glimepiride; LS: Least squares; MET: Metformin; OHAs: Oral hypoglycemic agents; SITA: Sitagliptin; SU: Sulfonylurea; SBP: Systolic blood pressure
All figures (7)
Figure 6
Figure 6
Percent change in body weight in clinical studies with canagliflozin as monotherapy or add-on therapy versus placebo/active comparators, sitagliptin, glimepiride and insulin. CANA: Canagliflozin; GLIM: Glimepiride; LS: Least squares; MET: Metformin; OHAs: Oral hypoglycemic agents; SITA: Sitagliptin; SU: Sulfonylurea
Figure 7
Figure 7
Change in systolic blood pressure in clinical studies with canagliflozin as monotherapy or add-on therapy versus placebo/active comparators, sitagliptin, glimepiride and insulin. CANA: Canagliflozin; GLIM: Glimepiride; LS: Least squares; MET: Metformin; OHAs: Oral hypoglycemic agents; SITA: Sitagliptin; SU: Sulfonylurea; SBP: Systolic blood pressure

References

    1. International Diabetes Federation. IDF Diabetes Atlas. 7th ed. Brussels, Belgium: International Diabetes Federation; 2015. [Last accessed on 2016 Jul 15]. Available from: .
    1. Ramachandran A, Snehalatha C, Shetty AS, Nanditha A. Trends in prevalence of diabetes in Asian countries. World J Diabetes. 2012;3:110–7.
    1. Mohan V, Shah SN, Joshi SR, Seshiah V, Sahay BK, Banerjee S, et al. Current status of management, control, complications and psychosocial aspects of patients with diabetes in India: Results from the DiabCare India 2011 Study. Indian J Endocrinol Metab. 2014;18:370–8.
    1. Kalra S, Unnikrishnan AG. Obesity in India: The weight of the nation. J Med Nutr Nutraceuticals. 2012;1:37–41.
    1. Pradeepa R, Anjana RM, Joshi SR, Bhansali A, Deepa M, Joshi PP, et al. Prevalence of generalized and abdominal obesity in urban and rural India – the ICMR-INDIAB Study (Phase-I) [ICMR- NDIAB-3] Indian J Med Res. 2015;142:139–50.
    1. Meshram II, Vishnu Vardhana Rao M, Sudershan Rao V, Laxmaiah A, Polasa K. Regional variation in the prevalence of overweight/obesity, hypertension and diabetes and their correlates among the adult rural population in India. Br J Nutr. 2016;115:1265–72.
    1. Anjana RM, Pradeepa R, Deepa M, Datta M, Sudha V, Unnikrishnan R, et al. Prevalence of diabetes and prediabetes (impaired fasting glucose and/or impaired glucose tolerance) in urban and rural India: Phase I results of the Indian Council of Medical Research-INdia DIABetes (ICMR-INDIAB) study. Diabetologia. 2011;54:3022–7.
    1. Little M, Humphries S, Patel K, Dodd W, Dewey C. Factors associated with glucose tolerance, pre-diabetes, and type 2 diabetes in a rural community of South India: A cross-sectional study. Diabetol Metab Syndr. 2016;8:21.
    1. Ferrannini E. The target of metformin in type 2 diabetes. N Engl J Med. 2014;371:1547–8.
    1. Yki-Järvinen H. Thiazolidinediones. N Engl J Med. 2004;351:1106–18.
    1. Groop LC. Sulfonylureas in NIDDM. Diabetes Care. 1992;15:737–54.
    1. Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: Systematic review and meta-analysis. JAMA. 2007;298:194–206.
    1. Swinnen SG, Hoekstra JB, DeVries JH. Insulin therapy for type 2 diabetes. Diabetes Care. 2009;32(Suppl 2):S253–9.
    1. Nicasio J, McFarlane SI. Early insulin therapy and the risk of cardiovascular disease in Type 2 diabetes. Therapy. 2005;2:685–8.
    1. Cook MN, Girman CJ, Stein PP, Alexander CM, Holman RR. Glycemic control continues to deteriorate after sulfonylureas are added to metformin among patients with type 2 diabetes. Diabetes Care. 2005;28:995–1000.
    1. Riedel AA, Heien H, Wogen J, Plauschinat CA. Secondary failure of glycemic control for patients adding thiazolidinedione or sulfonylurea therapy to a metformin regimen. Am J Manag Care. 2007;13:457–63.
    1. Riedel AA, Heien H, Wogen J, Plauschinat CA. Loss of glycemic control in patients with type 2 diabetes mellitus who were receiving initial metformin, sulfonylurea, or thiazolidinedione monotherapy. Pharmacotherapy. 2007;27:1102–10.
    1. Mitka M. More patients get good diabetes control, but only a minority meet all goals. JAMA. 2013;309:1335–6.
    1. Lawrence DB, Ragucci KR, Long LB, Parris BS, Helfer LA. Relationship of oral antihyperglycemic (sulfonylurea or metformin) medication adherence and hemoglobin HbA1c goal attainment for HMO patients enrolled in a diabetes disease management program. J Manag Care Pharm. 2006;12:466–71.
    1. Bailey CJ, Kodack M. Patient adherence to medication requirements for therapy of type 2 diabetes. Int J Clin Pract. 2011;65:314–22.
    1. Braga MF, Casanova A, Teoh H, Gerstein HC, Fitchett DH, Honos G, et al. Poor achievement of guidelines-recommended targets in type 2 diabetes: Findings from a contemporary prospective cohort study. Int J Clin Pract. 2012;66:457–64.
    1. Cernea S, Raz I. Therapy in the early stage: Incretins. Diabetes Care. 2011;34(Suppl 2):S264–71.
    1. Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355:2427–43.
    1. Fowler MJ. Diabetes treatment, part 2: Oral agents for glycemic management. Clin Diabetes. 2007;25:131–4.
    1. Korytkowski M. When oral agents fail: Practical barriers to starting insulin. Int J Obes Relat Metab Disord. 2002;26(Suppl 3):S18–24.
    1. Nakar S, Yitzhaki G, Rosenberg R, Vinker S. Transition to insulin in type 2 diabetes: Family physicians’ misconception of patients’ fears contributes to existing barriers. J Diabetes Complications. 2007;21:220–6.
    1. Nauck MA. Update on developments with SGLT2 inhibitors in the management of type 2 diabetes. Drug Des Devel Ther. 2014;8:1335–80.
    1. Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev. 2011;91:733–94.
    1. Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, et al. AACE/ACE comprehensive diabetes management algorithm 2015. Endocr Pract. 2015;21:438–47.
    1. Standards of medical care in diabetes-2015: Summary of revisions. Diabetes Care. 2015;38(Suppl):S4.
    1. Madhu S, Saboo B, Makkar BM, Reddy GC, Jana J, Panda JK, et al. RSSDI clinical practice recommendations for management of type 2 diabetes mellitus, 2015. Int J Diabetes Dev Ctries. 2015;35:1–71.
    1. Harper W, Clement M, Goldenberg R, Hanna A, Main A, et al. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Policies, guidelines and consensus statements: Pharmacologic management of type 2 diabetes-2015 interim update. Can J Diabetes. 2015;39:250–2.
    1. International Diabetes Federation. Managing Older People with Type 2 Diabetes Global Guideline. 2013. [Last accessed on 2016 Jul 15]. Available from: .
    1. National Institute for Health and Care Excellence. Canagliflozin, Dapagliflozin and Empagliflozin as Monotherapies for Treating Type 2 Diabetes. 2016. [Last accessed on 2016 Jul 15]. Available from: .
    1. National Institute for Health and Care Excellence. Canagliflozin in Combination Therapy for Treating Type 2 Diabetes. 2014. [Last accessed on 2016 Jul 15]. Available from: .
    1. INVOKANA® (Canagliflozin) Tablets. Highlights of Prescribing Information. 2016. [Last accessed on 2016 Oct 05]. Available from: .
    1. Plosker GL. Canagliflozin: A review of its use in patients with type 2 diabetes mellitus. Drugs. 2014;74:807–24.
    1. Seufert J. SGLT2 inhibitors-an insulin-independent therapeutic approach for treatment of type 2 diabetes: Focus on canagliflozin. Diabetes Metab Syndr Obes. 2015;8:543–54.
    1. Bhatia J, Gamad N, Bharti S, Arya DS. Canagliflozin-current status in the treatment of type 2 diabetes mellitus with focus on clinical trial data. World J Diabetes. 2014;5:399–406.
    1. Parveen R, Agarwal NB, Kaushal N, Mali G, Raisuddin S. Efficacy and safety of canagliflozin in type 2 diabetes mellitus: Systematic review of randomized controlled trials. Expert Opin Pharmacother. 2016;17:105–15.
    1. Devineni D, Curtin CR, Polidori D, Gutierrez MJ, Murphy J, Rusch S, et al. Pharmacokinetics and pharmacodynamics of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in subjects with type 2 diabetes mellitus. J Clin Pharmacol. 2013;53:601–10.
    1. Sha S, Devineni D, Ghosh A, Polidori D, Chien S, Wexler D, et al. Canagliflozin, a novel inhibitor of sodium glucose co-transporter 2, dose dependently reduces calculated renal threshold for glucose excretion and increases urinary glucose excretion in healthy subjects. Diabetes Obes Metab. 2011;13:669–72.
    1. Kalra S, Singh V, Nagrale D. Sodium-glucose cotransporter-2 inhibition and the glomerulus: A review. Adv Ther. 2016;33:1502–18.
    1. Singh SK, Gupta A. SGLT2 inhibitors for treatment of type 2 diabetes mellitus: Focus on canagliflozin. Muller J Med Sci Res. 2014;5:166.
    1. Polidori D, Sha S, Mudaliar S, Ciaraldi TP, Ghosh A, Vaccaro N, et al. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: Results of a randomized, placebo-controlled study. Diabetes Care. 2013;36:2154–61.
    1. Liang Y, Arakawa K, Ueta K, Matsushita Y, Kuriyama C, Martin T, et al. Effect of canagliflozin on renal threshold for glucose, glycemia, and body weight in normal and diabetic animal models. PLoS One. 2012;7:e30555.
    1. Stein P, Berg JK, Morrow L, Polidori D, Artis E, Rusch S, et al. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces post-meal glucose excursion in patients with type 2 diabetes by a non-renal mechanism: Results of a randomized trial. Metabolism. 2014;63:1296–303.
    1. Devineni D, Manitpisitkul P, Murphy J, Stieltjes H, Ariyawansa J, Di Prospero NA, et al. Effect of food on the pharmacokinetics of canagliflozin, a sodium glucose co-transporter 2 inhibitor, and assessment of dose proportionality in healthy participants. Clin Pharmacol Drug Dev. 2015;4:279–86.
    1. Devineni D, Vaccaro N, Polidori D, Stieltjes H, Wajs E. Single- and multiple-dose pharmacokinetics and pharmacodynamics of canagliflozin, a selective inhibitor of sodium glucose co-transporter 2, in healthy participants. Int J Clin Pharmacol Ther. 2015;53:129–38.
    1. Devineni D, Polidori D, Curtin C, Stieltjes H, Tian H, Wajs E. Single- and multiple-dose pharmacokinetics and pharmacodynamics of canagliflozin, a selective inhibitor of sodium glucose co-transporter 2, in healthy participants. Int J Clin Pharmacol Ther. 2015;53:129–38.
    1. Devineni D, Murphy J, Wang SS, Stieltjes H, Rothenberg P, Scheers E, et al. Absolute oral bioavailability and pharmacokinetics of canagliflozin: A microdose study in healthy participants. Clin Pharmacol Drug Dev. 2015;4:95–304.
    1. Devineni D, Polidori D. Clinical pharmacokinetic, pharmacodynamic, and drug-drug interaction profile of canagliflozin, a sodium-glucose co-transporter 2 inhibitor. Clin Pharmacokinet. 2015;54:1027–41.
    1. Devineni D, Manitpisitkul P, Murphy J, Skee D, Wajs E, Mamidi RN, et al. Effect of canagliflozin on the pharmacokinetics of glyburide, metformin, and simvastatin in healthy participants. Clin Pharmacol Drug Dev. 2015;4:226–36.
    1. FARXIGA® (Dapagliflozin) Tablets. Highlights of Prescribing Information. 2014. [Last accessed on 2016 Oct 05]. Available from: .
    1. JARDIANCE® (Empagliflozin) Tablets. Highlights of Prescribing Information. 2014. [Last accessed on 2016 Oct 05]. Available from: .
    1. Haas B, Eckstein N, Pfeifer V, Mayer P, Hass MD. Efficacy, safety and regulatory status of SGLT2 inhibitors: Focus on canagliflozin. Nutr Diabetes. 2014;4:e143.
    1. European Medicines Agency. Invokana 100 and 300 mg Filmcoated Tablets: Summary of Product Characteristics. 2013. [Last accessed on 2016 Jul 15]. Accessed from: .
    1. Central Drugs Standard Control Organization. List of FDC and new drugs approved for marketing in India. [Last accessed on 2016 Jul 15]. Available from: .
    1. Stenlöf K, Cefalu WT, Kim KA, Alba M, Usiskin K, Tong C, et al. Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes Obes Metab. 2013;15:372–82.
    1. Stenlöf K, Cefalu WT, Kim KA, Jodar E, Alba M, Edwards R, et al. Long-term efficacy and safety of canagliflozin monotherapy in patients with type 2 diabetes inadequately controlled with diet and exercise: Findings from the 52-week CANTATA-M study. Curr Med Res Opin. 2014;30:163–75.
    1. Yang T, Lu M, Ma L, Zhou Y, Cui Y. Efficacy and tolerability of canagliflozin as add-on to metformin in the treatment of type 2 diabetes mellitus: A meta-analysis. Eur J Clin Pharmacol. 2015;71:1325–32.
    1. Sun YN, Zhou Y, Chen X, Che WS, Leung SW. The efficacy of dapagliflozin combined with hypoglycaemic drugs in treating type 2 diabetes mellitus: Meta-analysis of randomised controlled trials. BMJ Open. 2014;4:e004619.
    1. Lavalle-González FJ, Januszewicz A, Davidson J, Tong C, Qiu R, Canovatchel W, et al. Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: A randomised trial. Diabetologia. 2013;56:2582–92.
    1. Schernthaner G, Gross JL, Rosenstock J, Guarisco M, Fu M, Yee J, et al. Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea: A 52-week randomized trial. Diabetes Care. 2013;36:2508–15.
    1. Cefalu WT, Leiter LA, Yoon KH, Arias P, Niskanen L, Xie J, et al. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet. 2013;382:941–50.
    1. Leiter LA, Yoon KH, Arias P, Langslet G, Xie J, Balis DA, et al. Canagliflozin provides durable glycemic improvements and body weight reduction over 104 weeks versus glimepiride in patients with type 2 diabetes on metformin: A randomized, double.blind, phase 3 study. Diabetes Care. 2015;38:355–64.
    1. Forst T, Guthrie R, Goldenberg R, Yee J, Vijapurkar U, Meininger G, et al. Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone. Diabetes Obes Metab. 2014;16:467–77.
    1. Wilding JP, Charpentier G, Hollander P, González-Gálvez G, Mathieu C, Vercruysse F, et al. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sulphonylurea: A randomised trial. Int J Clin Pract. 2013;67:1267–82.
    1. Devineni D, Morrow L, Hompesch M, Skee D, Vandebosch A, Murphy J, et al. Canagliflozin improves glycaemic control over 28 days in subjects with type 2 diabetes not optimally controlled on insulin. Diabetes Obes Metab. 2012;14:539–45.
    1. Neal B, Perkovic V, de Zeeuw D, Mahaffey KW, Fulcher G, Ways K, et al. Efficacy and safety of canagliflozin, an inhibitor of sodium-glucose cotransporter 2, when used in conjunction with insulin therapy in patients with type 2 diabetes. Diabetes Care. 2015;38:403–11.
    1. Rodbard HW, Seufert J, Aggarwal N, Cao A, Fung A, Pfeifer M, et al. Efficacy and safety of titrated canagliflozin in patients with type 2 diabetes mellitus inadequately controlled on metformin and sitagliptin. Diabetes Obes Metab. 2016;18:812–9.
    1. Fulcher G, Matthews DR, Perkovic V, de Zeeuw D, Mahaffey KW, Mathieu C, et al. Efficacy and safety of canagliflozin when used in conjunction with incretin-mimetic therapy in patients with type 2 diabetes. Diabetes Obes Metab. 2016;18:82–91.
    1. Kumar KM, Mohan V, Sethi B, Gandhi P, Bantwal G, Xie J, et al. PO422 efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from India. Diabetes Res Clin Pract. 2014;106(Suppl 1):S260–1.
    1. Prasanna Kumar KM, Mohan V, Sethi B, Gandhi P, Bantwal G, Xie J, et al. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from India. Indian J Endocrinol Metab. 2016;20:372–80.
    1. Inagaki N, Kondo K, Yoshinari T, Maruyama N, Susuta Y, Kuki H. Efficacy and safety of canagliflozin in Japanese patients with type 2 diabetes: A randomized, double-blind, placebo-controlled, 12-week study. Diabetes Obes Metab. 2013;15:1136–45.
    1. Bode B, Stenlöf K, Sullivan D, Fung A, Usiskin K. Efficacy and safety of canagliflozin treatment in older subjects with type 2 diabetes mellitus: A randomized trial. Hosp Pract. 2013;41:72–84.
    1. Bode B, Stenlöf K, Harris S, Sullivan D, Fung A, Usiskin K, et al. Long-term efficacy and safety of canagliflozin over 104 weeks in patients aged 55-80 years with type 2 diabetes. Diabetes Obes Metab. 2015;17:294–303.
    1. Wilding JP, Blonde L, Leiter LA, Cerdas S, Tong C, Yee J, et al. Efficacy and safety of canagliflozin by baseline HbA1c and known duration of type 2 diabetes mellitus. J Diabetes Complications. 2015;29:438–44.
    1. Pacou M, Taieb V, Abrams KR, Diels J, Van Sanden S, Garg M, et al. Bayesian network meta-analysis to assess the relative efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin. Value Health. 2013;; 16:A609.
    1. Schroeder M, Taieb V, Pacou M, Ho S, Nielsen AT, Schubert A, et al. Stockholm, Sweden: 2015. Sep 14-18, A Network meta-analysis to assess options for treatment intensification for patients with type 2 diabetes inadequately controlled on dual therapy. Poster presented at the 51st annual meeting of the European Association for the Study of Diabetes (EASD)
    1. Pacou M, Taieb V, Abrams KR, Diels J, Van Sanden S, Garg M, et al. Bayesian network meta-analysis to assess the relative efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on metformin and sulphonylurea (MET+SU) Value Health. 2013;16:A431.
    1. Taieb V, Pacou M, Schroeder M, Nielsen AT, Schubert A, Neslusan C. Milan, Italy: 2015. Nov 7-11, A Network meta-analysis (NMA) to assess the longer-term relative efficacy of canagliflozin in patients with type 2 diabetes inadequately controlled on metformin. Poster presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 18th Annual European Congress.
    1. van Sanden S, Diels J, Guillon P, Nielsen AT. Bayesian network meta-analysis (NMA) to assess relative efficacy of canagliflozin (CANA) versus glucagon-like peptide-1 (GLP-1) agonists in dual and triple therapy in patients with type 2 diabetes mellitus (T2DM) Value Health. 2015;18:A54.
    1. Bays HE, Weinstein R, Law G, Canovatchel W. Effects in overweight and obese subjects without diabetes mellitus. Obesity (Silver Spring) . 2014;22:1042–9.
    1. Weir MR, Januszewicz A, Gilbert RE, Vijapurkar U, Kline I, Fung A, et al. Effect of canagliflozin on blood pressure and adverse events related to osmotic diuresis and reduced intravascular volume in patients with type 2 diabetes mellitus. J Clin Hypertens (Greenwich) 2014;16:875–82.
    1. Seufert J. SGLT-2 inhibition with canagliflozin: A new option for the treatment of type 2 diabetes. Dtsch Med Wochenschr. 2014;139(Suppl 2):S52–8.
    1. Baker WL, Smyth LR, Riche DM, Bourret EM, Chamberlin KW, White WB. Effects of sodium-glucose co-transporter 2 inhibitors on blood pressure: A systematic review and meta-analysis. J Am Soc Hypertens. 2014;8:262–75.e9.
    1. Mikhail N. Place of sodium-glucose co-transporter type 2 inhibitors for treatment of type 2 diabetes. World J Diabetes. 2014;5:854–9.
    1. Summary of Product Characteristics of INVOKANA. UK: Janssen-Cilag Ltd; 2015. [Last accessed on 2016 Jul 151]. Available from: .
    1. Neal B, Perkovic V, de Zeeuw D, Mahaffey KW, Fulcher G, Stein P, et al. Rationale, design, and baseline characteristics of the Canagliflozin Cardiovascular Assessment Study (CANVAS) – a randomized placebo-controlled trial. Am Heart J. 2013;166:217–23.e11.
    1. CANVAS-R. [Last accessed on 2016 Jul 15]. Available from: .
    1. Usiskin K, Kline I, Fung A, Mayer C, Meininger G. Safety and tolerability of canagliflozin in patients with type 2 diabetes mellitus: Pooled analysis of phase 3 study results. Postgrad Med. 2014;126:16–34.
    1. Sobel JD, Goldenberg RM, Khunti K, Davies MJ, Vijapurkar U, Meininger G. Incidence of genital mycotic infections decreases over time in patients with type 2 diabetes mellitus treated with canagliflozin over 2 years. Diabetes. 2015;64(Suppl 1):A1178.
    1. Goldenberg RM, Sobel JD, Khunti K, Davies MJ, Vijapurkar U, Meininger G. Vancouver, BC, Canada: 2015. Incidence of genital mycotic infections and urinary tract infections in patients with type 2 diabetes mellitus treated with canagliflozin over 2 years. Poster presented at the 23rd World Diabetes Congress of the International Diabetes Federation (IDF); 30 November-4 December.
    1. Sinclair A, Bode B, Harris S, Vijapurkar U, Mayer C, Fung A, et al. Efficacy and safety of canagliflozin compared with placebo in older patients with type 2 diabetes mellitus: A pooled analysis of clinical studies. BMC Endocr Disord. 2014;14:37.
    1. Nicolle LE, Capuano G, Fung A, Usiskin K. Urinary tract infection in randomized phase III studies of canagliflozin, a sodium glucose co-transporter 2 inhibitor. Postgrad Med. 2014;126:7–17.
    1. Janssen Research and Development LLC. Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants with Diabetic Nephropathy (CREDENCE). US National Institutes of Health. 2014. [Last accessed on 2016 Jul 15]. Available from: .
    1. U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA Warns that SGLT2 Inhibitors for Diabetes May Result in a Serious Condition of Too Much Acid in the Blood. [Last accessed on 2016 Jul 15]. Available from: .
    1. Soni H. Euglycemic ketoacidosis and sodium glucose co-transporter 2 inhibitors: Is this novel class safe for the diabetic patients? MOJ Toxicol. 2015;1:21.
    1. Kalra S, Sahay R, Gupta Y. Sodium glucose transporter 2 (SGLT2) inhibition and ketogenesis. Indian J Endocrinol Metab. 2015;19:524–8.
    1. Erondu N, Desai M, Ways K, Meininger G. Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program. Diabetes Care. 2015;38:1680–6.
    1. Handelsman Y, Henry RR, Bloomgarden ZT, Dagogo-Jack S, DeFronzo RA, Einhorn D, et al. American Association of Clinical Endocrinologists and American College of Endocrinology position statement on the association of SGLT-2 inhibitors and diabetic ketoacidosis. Endocr Pract. 2016;22:753–62.
    1. Watts NB, Bilezikian JP, Usiskin K, Edwards R, Desai M, Law G, et al. Effects of canagliflozin on fracture risk in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2016;101:157–66.
    1. Food and Drug Administration. FDA Drug Safety Communication: Interim Clinical Trial Results Find Increased Risk of Leg and Foot Amputations, Mostly Affecting the Toes, with the Diabetes Medicine Canagliflozin (Invokana, Invokamet); FDA to Investigate. [Last accessed on 2016 Jul 15]. Available from: .
    1. Drug Safety Alert for Canagliflozin. [Last accessed on 2016 Jul 15]. Available from:
    1. Santoleri F, Sorice P, Lasala R, Costantini A. Liraglutide vs. exenatide: Patient adherence, medication persistence and economic evaluation in the treatment of type 2 diabetes mellitus. Pharmacol Pharm. 2014;5:332–9.
    1. Jain R, Cai J, Fu AC, Chow W, Tan H. Real world (RW) glycemic control and medication adherence among patients with type 2 diabetes mellitus (T2DM) initiated on canagliflozin. Poster Presentation. American Diabetes Association, 76th scientific sessions. New Orleans, Louisiana: 2016. p. 1161.
    1. Jermendy G, Wittmann I, Nagy L, Kiss Z, Rokszin G, Abonyi-Tóth Z, et al. Persistence of initial oral antidiabetic treatment in patients with type 2 diabetes mellitus. Med Sci Monit. 2012;18:CR72–7.
    1. Stephens JM, Blak BT, Gold KF, Botteman MF, Pashos CL, Walkinshaw CS, et al. Persistence patterns with oral hypoglycemic agents in type 2 diabetes. JCOM. 2002;9:491–9.
    1. Diels J, Neslusan C. Comparative persistency with newer agents used to treat type 2 diabetes (T2DM) in the United States: Canagliflozin versus dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists. Value Health. 2015;18:A68–9.
    1. Cai J, Wang Y, Baser O, Xie L, Diels J, Neslusan C, et al. Comparative persistence with antihyperglycemic agents (AHA) used to treat type 2 diabetes mellitus (T2DM) in the real world. Poster Presentation. American Diabetes Association, 76th scientific sessions. New Orleans, Louisiana: 2016. p. 1155.
    1. Buysman EK, Liu F, Hammer M, Langer J. Impact of medication adherence and persistence on clinical and economic outcomes in patients with type 2 diabetes treated with liraglutide: A retrospective cohort study. Adv Ther. 2015;32:341–55.
    1. Wilke T, Groth A, Berg B, Sikirica M, Martin AA, Fuchs A, et al. Non-adherence and non-persistence related to Glp-1 therapy in patients with diabetes mellitus type 2 (T2dm): Analysis of a large german claims-based dataset and comparison to oral anti-diabetics. Value Health. 2014;17:A359.
    1. Foley JE, Jordan J. Weight neutrality with the DPP-4 inhibitor, vildagliptin: Mechanistic basis and clinical experience. Vasc Health Risk Manag. 2010;6:541–8.
    1. Campbell RK, Cobble ME, Reid TS, Shomali ME. Distinguishing among incretin-based therapies. Pathophysiology of type 2 diabetes mellitus: Potential role of incretin-based therapies. J Fam Pract. 2010;59(9 Suppl 1):S5–9.
    1. Buysman EK, Chow W, Henk HJ, Rupnow MF. Characteristics and short-term outcomes of patients with type 2 diabetes mellitus treated with canagliflozin in a real-world setting. Curr Med Res Opin. 2015;31:137–43.
    1. Chow W, Buysman EK, Rupnow MF, Henk HJ. PDB16. Real-world treatment patterns of antihyperglycemic agents among patients with type 2 diabetes mellitus (T2DM) initiated on canagliflozin. Value Health. 2015;18:A55.
    1. Lefebvre P, Pilon D, Robitaille MN, Lafeuille MH, Chow W, Pfeifer M, et al. Glycated hemoglobin (HbA1c) control in patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin in a real-world setting. Value Health. 2015;18:A57.
    1. Meckley LM, Miyasato G, Kokkotos F, Bailey RA. Real-world canagliflozin utilization: Impact on glycemic control in patients with type 2 diabetes mellitus. Value Health. 2015;18:A54–5.
    1. Thayer S, Chow W, Korrer S, Aguilar R. Real-world evaluation of glycemic control among patients with type 2 diabetes mellitus treated with canagliflozin versus dipeptidyl peptidase-4 inhibitors. Curr Med Res Opin. 2016;32:1087–96.
    1. Bacon T, Willis M, Johansen P, Neslusan C, Nuhoho S, Worbes-Cerezo M. The cost-effectiveness of canagliflozin verse liraglutide in patients with type 2 diabetes (T2dm) failing to achieve glycaemic control on metformin monotherapy in Ireland. Value Health. 2014;17:A345.
    1. Troelsgaard A, Pitcher A, Granados D, Hemels M, Lloyd A. The Cost-effectiveness of canagliflozin compared with liraglutide in patients with type 2 diabetes inadequately controlled with metformin and sulfonylurea in France. Value Health. 2014;17:A346–7.
    1. Neslusan C, Teschemaker A, Johansen P, Willis M, Valencia-Mendoza A, Puig A. Cost-effectiveness of canagliflozin versus sitagliptin as add-on to metformin in patients with type 2 diabetes mellitus in Mexico. Value Health Reg Issues. 2015;8C:8–19.

Source: PubMed

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