Commentary
Policies,Guidelines and Connsus Statements:Pharmacologic Management of Type 2Diabetes e 2015Interim Update
Canadian Diabetes Association Clinical Practice Guidelines Expert Committee
The initial draft of this commentary was prepared by William Harper MD,FRCPC,Maureen Clement MD,CCFP,Ronald Goldenberg MD,FRCPC,FACE,Amir Hanna MB,BCh,FRCPC,FACP,Andrea Main BScPhm,CDE,Ravi Retnakaran MD,MSc,FRCPC,Diana Sherifali RN,PhD,CDE,Vincent Woo MD,FRCPC,Jean-François Yale MD,CSPQ,FRCPC,and Alice Y.Y.Cheng MD,FRCPC on behalf of the Steering
Committee for the Canadian Diabetes Association 2013Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada
a r t i c l e i n f o
Article history:
burglarReceived 13May 2015Accepted 13May 2015
The process of the development of the Canadian Diabetes Association 2013Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada included provisions to update individual chapters prior to the planned published revision in 2018(1).An updated literature arch that focud on new evidence published since the development of the 2013guidelines yielded 1787citations.After review of the citations,the chapter authors advid the steering and executive committees that there were no signi ficant changes in evidence to warrant the formulation of any new recommendations or the revision of any current recommendations.As such,it was recommended that a full update of the chapter be deferred until the planned revision of the entire Clinical Practice Guidelines in 2018.
However,the steering committee decided it was warranted to publish an interim commentary addressing the approval,in Canada,of a new class of antihyperglycemic agents d sodium-gluco linked transporter 2(SGLT2)inhibitors d for the pharmacologic management of diabetes.Two agents from this class have received notice of compliance by Health Canada since the publication of the 2013guidelines:canagli flozin and dapagli flozin (2).This update was deemed necessary by the steering committee becau the addition of a new class of pharmacologic therapy reprents a signi ficant change in the management options for diabetes,yet the next complete update of the guidelines is still 3years away.
SGLT2inhibitors block gluco transport in the proximal renal tubule,which results in the urinary excretion of gluco,thereby lowering blood gluco and body weight (3,4).Network meta-analys show that,when added to metformin,SGLT2
inhibitors generally have similar or slightly better ef ficacy in lowering glycated hemoglobin levels than do other anti-hyperglycemic agents (5,6).The incidence of hypoglycemia with SGLT2inhibitors is rare unless they are ud in combination with insulin or sulfonylureas (3).Becau of the glycosuria resulting from the u of the agents,there is an incread risk for urinary tract infections,genital mycotic infections and hypotension caud by osmotic diuresis (3).Although SGLT2inhibitors lower blood pressure (3)and rai high-density lipoprotein cholesterol,they elevate low-density lipoprotein cholesterol modestly (7,8),and their cardiovascular safety remains unknown and awaits long-term clinical trials.An imbalance in bladder cancer was noted with dapagli flozin in early clinical trials;however,many of the subjects with bladder cancer had pre-existing hematuria (9).There have been reported cas of diabetic ketoacidosis,without the usual elevated blood gluco,in patients with type 2diabetes being treated with SGLT2inhibitors (10e 13).The cas are rare and further details await ongoing reviews.Patients on an SGLT2inhibitor with symptoms of breathing dif ficulty,naua,vomiting,abdominal pain,confusion or fatigue,even in the abnce of high
rapeedblood gluco,should be evaluated for ketoaci-dosis.If the ketoacidosis is con firmed,appropriate measures should be undertaken to correct the acidosis.The SGLT2inhibitor therapy should be interrupted and its subquent long term u should be reassd (10,13).U of SGLT2inhibitors is not currently approved for type 1diabetes.Figure 1sum-marizes the therapeutic considerations for SGLT2inhibitor therapy in the management of type 2diabetes mellitus.The ef ficacy of SGLT2inhibitors with respect to gluco lowering
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Contents lists available at ScienceDirect
Canadian Journal of Diabetes
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1499-2671/$e e front matter Ó2015Canadian Diabetes Association dx.doi/10.1016/j.jcjd.2015.05.009
Can J Diabetes 39(2015)250e 252
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Figure 1.Management of hyperglycemia in type 2diabetes.A1C ,glycated hemoglobin;BG ,blood gluco;CHF ,congestive heart failure;DPP-4,dipeptidyl peptida 4;GI ,gastrointestinal;GLP-1,glucagon-like peptide 1;SGLT2,sodium gluco linked transporter 2;TZD ,thiazolidinedione;UTI ,urinary tract infection.
W.Harper /Can J Diabetes 39(2015)250e 252251
heirdependent on their effects on urinary gluco excretion,which is attenuated in patients with renal dysfunction (14).Figure 2summarizes the contraindications to u of SGLT2inhibitors in patients with declining renal function bad on product monographs.
In the pharmacologic management of type 2diabetes,metformin remains the first agent of choice (15).SGLT2inhibitors are a new class of antihyperglycemic agents available for the treatment of diabetes in Canada,and their u can be considered in management plans individualized to meet patients ’characteristics,as outlined in Figure 1.References
1.Booth G,Cheng AYY.Canadian Diabetes Association 2013Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada:Methods.Can J Diabetes 2013;37(Supp l1):S4e 7.
2.Health Canada Notice of Compliance Databa.a/dhp-mps/prodpharma/notices-avis/index-eng.php .Accesd March 6,2015.
3.Vasilakou D,Karagiannis T,Athanasiadou E,et al.Sodium-gluco cotransporter 2inhibitors for type 2diabetes.A systematic review and meta-analysis.Ann Intern Med 2013;159:262e 7
4.
4.Bolinder J,Ljunggren O,Johansson L,et al.Dapagli flozin maintains glycaemic control while reducing weight and body fat mass over 2years in patients with type 2diabetes mellitus inadequately controlled on metformin.Diabetes Obes Metab 2014;16(2):159e 69.
5.Barnett AH,Orme ME,Fenici P,et al.Systematic review and network meta-analysis to compare dapagli flozin to other diabetes medications in combination with metformin for adults with type 2diabetes.Intern Med 2014;S6:S6e 00
6.dx.doi/10.4172/2165-8048.S6-006. 6.Pacou M,Taieb V,Abrams KR,et al.Bayesian network meta-analysis to asss relative ef ficacy and safety of canagli flozin in patients with type 2diabetes mellitus (T2DM)inadequately controlled with metformin.Value Health 2013;16:A609.
7.Yang XP,Lai D,Zhong XY,et al.Ef ficacy and safety of canaglilozin in subjects with type 2diabetes:Systematic review and meta-analysis.Eur J Clin Pharmacol 2014;70:1149e 58.
8.Bode B,Stenlof K,Harris S,et al.Long-term ef ficacy and safety of canagli flozin over 104weeks in patients aged 55-80years with type 2diabetes.Diabetes Obes Metab 2015;17:294e 303.
9.Lin HW,Tng CH.A review on the relationship between SGLT2inhibitors and cancer.Int J Endocrinol 2014;2014:719578.doi:10.1155/2014/71958.Epub 2014Aug 31.
10.U.S.Food and Drug Administration Drug Safety Communication.FDA warns
that SGLT2inhibitors for diabetes may result in a rious condition of too much acid in the blood.Available from v/Drugs/DrugSafety/ucm446845.htm?source=govdelivery&utm_medium=email&utm_source=gov delivery .Accesd 15May 2015.
11.European Medicines Agency Review Notice.Review of diabetes medicines
called SGLT2inhibitors started.Available a.europa.eu/ema/index.jspcurl=pages/medicines/human/referrals/SGLT2_inhibitors/human_referral_prac_000052.jsp&mid=WC0b01ac05805c516f .Accesd 19June 2015.12.Peters AL,Buschur EO,Bu JB,et al.Euglycemic diabetic ketoacidosis:A
potential complication of treatment with sodium-gluco cotransporter 2inhibition.Diabetes Care 2015;DOI:10.2337/dc15-0843.Published online June 15,2015.
13.Health Canada Information Update a/ahc-asc/media/用环保材料做衣服
advisories-avis/forxiga-invokana-eng.php .Accesd June 22,2015.
14.Yale JF,Bakris G,Cariou B,et al.Ef ficacy and safety of canagli flozin over 52
weeks in patients with type 2diabetes mellitus and chronic kidney dia.Diabetes Obes Metab 2014;16:1016e 27.
15.Harper W,Clement M,Goldenberg R,et al.Canadian Diabetes
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Figure 2.Antihyperglycemic medications and renal function.Bad on product monograph precautions.CKD ,chronic kidney dia;GFR ,glomerular filtration rate;TZD ,thiazolidinedione.Designed by and ud with the permission of Jean-François Yale MD CSPQ FRCPC.
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