diabetes management in 2017 · discuss further updates in diabetes management in 2017 dpp-4...
TRANSCRIPT
Diabetes Management in 2017
AliceYYCheng,MD,FRCPC
Twi4er:@AliceYYCheng
Objec;ves
Bytheendofthissession,youwillbeableto:
1. Describethemajorlandmarkcardiovascularoutcometrialsindiabetesthatshouldchangeprac;ce
2. U;lizetherecommenda;onsfromrecentupdatestotheDiabetesCanadaclinicalprac;ceguidelines
3. Discussfurtherupdatesindiabetesmanagementin2017
DPP-4inhibitorGLP-1receptor
agonistInsulin
Insulinsecretatogue
SGLT2inhibitor
MeWormin
Thiazolidinedione
GLP-1receptoragonist
DPP-4inhibitorGLP-1receptor
agonist
MeWormin
Alpha-glucosidaseinhibitor:
carbohydrateabsorp;on
Adapted from: Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 2009; 58(4):773-95.
Addanotherclassofagentbestsuitedtotheindividual(agentslistedinalphabe.calorder):
Class Rela8veA1CLowering
Hypo-glycemia
Weight EffectinCardiovascularOutcomeTrial
Othertherapeu8cconsidera8ons Cost
α-glucosidaseinhibitor(acarbose)
↓ Rare Neutralto↓
Improvedpostprandialcontrol,GIside-effects $$
DPP-4Inhibitors ↓↓
Rare
Neutralto↓
alo,saxa,sita:
Neutral
Cau;onwithsaxaglip;ninheartfailure
$$$
GLP-1Ragonists ↓↓to↓↓↓ Rare ↓↓
lira:SuperiorityinT2DMpa;entswithclinicalCVD
lixi:Neutral
GIside-effects
$$$$
Insulin ↓↓↓ Yes ↑↑ Neutral(glar) Nodoseceiling,flexibleregimens $-$$$$
Insulinsecretagogue:Megli;nideSulfonylurea
↓↓↓↓
YesYes
↑↑
LesshypoglycemiaincontextofmissedmealsbutusuallyrequiresTIDtoQIDdosingGliclazideandglimepirideassociatedwithlesshypoglycemiathanglyburide
$$$
SGLT2inhibitors ↓↓to↓↓↓
Rare ↓↓
empa:SuperiorityinT2DMpa;entswithclinicalCVD
Genitalinfec;ons,UTI,hypotension,dose-relatedchangesinLDL-C,cau;onwithrenaldysfunc;onandloopdiure;cs,dapagliflozinnottobeusedifbladdercancer,rarediabe;cketoacidosis(mayoccurwithnohyperglycemia)
$$$
Thiazolidinediones ↓↓ Rare ↑↑ Neutral CHF,edema,fractures,rarebladdercancer(pioglitazone),cardiovascularcontroversy(rosiglitazone),6-12weeksrequiredformaximaleffect
$$
Weightlossagent(orlistat)
↓ None ↓ GIsideeffects $$$
alo=aloglip;n;glar=glargine;saxa=saxaglip;n;sita=sitaglip;n;lira=liraglu;de;lixi=lixisena;de;empa=empagliflozin 11/2016
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association
2016
Published online on November 2016
6
Primary outcome: 3-point MACE: CV death, non-fatal MI or non-fatal stroke
7
Empagliflozin (pooled) HR 0.86
(95.02% CI 0.74, 0.99) p=0.0382*
Cumulative incidence function. MACE, Major Adverse Cardiovascular Event; HR, hazard ratio. * Two-sided tests for superiority were conducted (statistical significance was indicated if p≤0.0498)
Empagliflozin 25 mg HR 0.86 (95% CI 0.73, 1.02),p=0.0865
Empagliflozin 10 mg
HR 0.85 (95% CI 0.72, 1.01), p=0.0668
Zinman B, Wanner C, Lachin JM, et al. N Engl J Med Sep 17, 2015. 10.1056/NEJMoa1504720
Patients with event/analysed Empagliflozin Placebo HR (95% CI) p-value
3-point MACE 490/4687 282/2333 0.86 (0.74, 0.99)* 0.0382
CV death 172/4687 137/2333 0.62 (0.49, 0.77) <0.0001
Non-fatal MI 213/4687 121/2333 0.87 (0.70, 1.09) 0.2189
Non-fatal stroke 150/4687 60/2333 1.24 (0.92, 1.67) 0.1638
0.25 0.50 1.00 2.00
CV death, MI and stroke
8
Favours empagliflozin Favours placebo
Cox regression analysis. MACE, Major Adverse Cardiovascular Event; HR, hazard ratio; CV, cardiovascular; MI, myocardial infarction *95.02% CI
Hospitalisation for heart failure
9
Empagliflozin (pooled) HR 0.65
(95% CI 0.50, 0.85) p=0.0017
Cumulative incidence function. HR, hazard ratio
Empagliflozin 10 mg HR 0.62 (95% CI 0.45, 0.86), p=0.0044
Empagliflozin 25 mg HR 0.68 (95% CI 0.50, 0.93), p=0.0166
Zinman B, Wanner C, Lachin JM, et al. N Engl J Med Sep 17, 2015. 10.1056/NEJMoa1504720
All-cause mortality
10
Empagliflozin (pooled HR 0.68
(95% CI 0.57, 0.82) p<0.0001
NNT = 39
For 3 years
Kaplan-Meier estimate. HR, hazard ratio
Empagliflozin 10 mg HR 0.70 (95% CI 0.56, 0.87), p=0.0013
Empagliflozin 25 mg HR 0.67 (95% CI 0.54, 0.83), p=0.0003
Zinman B, Wanner C, Lachin JM, et al. N Engl J Med Sep 17, 2015. 10.1056/NEJMoa1504720
EMPA-REG OUTCOME: Number needed to treat to prevent one…
CV: cardiovascular; MACE: major adverse cardiovascular event.
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med Sep 17, 2015. doi: 10.1056/NEJMoa1504720
63 45 39
CV death MACE All-cause death
For 3 years
Primary outcome CV death, non-fatal myocardial infarction, or non-fatal stroke
The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke. The cumulative incidences were estimated with the use of the Kaplan–Meier method, and the hazard ratios with the use of the Cox proportional-hazard regression model. The data analyses are truncated at 54 months, because less than 10% of the patients had an observation time beyond 54 months. CI: confidence interval; CV: cardiovascular; HR: hazard ratio.
Presented at the American Diabetes Association 76th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.
CV Death, Non-fatal MI, Non-fatal stroke
*95.02% CI. CV: cardiovascular; Empa: empaglifloin; Lira: liraglutide; MACE: major adverse cardiovascular event; MI: myocardial infarction; Pbo: placebo.
Presented at the American Diabetes Association 76th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.
All-cause death
The cumulative incidences were estimated with the use of the Kaplan–Meier method, and the hazard ratios with the use of the Cox proportional-hazard regression model. The data analyses are truncated at 54 months, because less than 10% of the patients had an observation time beyond 54 months. CI: confidence interval; HR: hazard ratio.
Presented at the American Diabetes Association 76th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.
LEADER: Number needed to treat to prevent one…
CV: cardiovascular; MACE: major adverse cardiovascular event.
Marso S et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes N Engl J Med June 2016 doi: 10.1056/NEJMoa160382. Presented at the American Diabetes Association 76th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.
Start metformin immediately
Consider initial combination with another antihyperglycemic agent
Start lifestyle intervention (nutrition therapy and physical activity) +/- Metformin
A1C <8.5% Symptomatic hyperglycemia with metabolic decompensation A1C ≥8.5%
Initiate insulin +/- metformin
If not at glycemic target (2-3 mos)
Start / Increase metformin
If not at glycemic targets
L I F E S T Y L E
Add another agent best suited to the individual by prioritizing patient characteristics:
Degree of hyperglycemia Risk of hypoglycemia Overweight or obesity Cardiovascular disease or multiple risk factors Comorbidities (renal, CHF, hepatic) Preferences & access to treatment
See next page…
AT DIAGNOSIS OF TYPE 2 DIABETES
Consider relative A1C lowering Rare hypoglycemia Weight loss or weight neutral Effect on cardiovascular outcome See therapeutic considerations, consider eGFR See cost column; consider access
PATIENT CHARACTERISTIC CHOICE OF AGENT
PRIORITY: Clinical Cardiovascular Disease
Antihyperglycemic agent with demonstrated CV outcome benefit (empagliflozin, liraglutide)
11/2016
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association
Add another agent best suited to the individual by prioritizing patient characteristics:
Degree of hyperglycemia Risk of hypoglycemia Overweight or obesity CV disease or multiple risk factors Comorbidities (renal, CHF, hepatic) Preferences & access to treatment
Consider relative A1C lowering Rare hypoglycemia Weight loss or weight neutral Effect on cardiovascular outcome See therapeutic considerations See cost column; consider access
PATIENT CHARACTERISTIC CHOICE OF AGENT
PRIORITY: Clinical Cardiovascular Disease
Antihyperglycemic agent with demonstrated CV outcome benefit (empagliflozin, liraglutide)
2016
If not at glycemic target
From prior page…
• Add another agent from a different class • Add/Intensify insulin regimen
Make timely adjustments to attain target A1C within 3-6 months
L I F E S T Y L E
11/2016
Addanotherclassofagentbestsuitedtotheindividual(agentslistedinalphabe.calorder):
Class Rela8veA1CLowering
Hypo-glycemia
Weight EffectinCardiovascularOutcomeTrial
Othertherapeu8cconsidera8ons Cost
α-glucosidaseinhibitor(acarbose)
↓ Rare Neutralto↓
Improvedpostprandialcontrol,GIside-effects $$
DPP-4Inhibitors ↓↓
Rare
Neutralto↓
alo,saxa,sita:
Neutral
Cau;onwithsaxaglip;ninheartfailure
$$$
GLP-1Ragonists ↓↓to↓↓↓ Rare ↓↓
lira:SuperiorityinT2DMpa;entswithclinicalCVD
lixi:Neutral
GIside-effects
$$$$
Insulin ↓↓↓ Yes ↑↑ Neutral(glar) Nodoseceiling,flexibleregimens $-$$$$
Insulinsecretagogue:Megli;nideSulfonylurea
↓↓↓↓
YesYes
↑↑
LesshypoglycemiaincontextofmissedmealsbutusuallyrequiresTIDtoQIDdosingGliclazideandglimepirideassociatedwithlesshypoglycemiathanglyburide
$$$
SGLT2inhibitors ↓↓to↓↓↓
Rare ↓↓
empa:SuperiorityinT2DMpa;entswithclinicalCVD
Genitalinfec;ons,UTI,hypotension,dose-relatedchangesinLDL-C,cau;onwithrenaldysfunc;onandloopdiure;cs,dapagliflozinnottobeusedifbladdercancer,rarediabe;cketoacidosis(mayoccurwithnohyperglycemia)
$$$
Thiazolidinediones ↓↓ Rare ↑↑ Neutral CHF,edema,fractures,rarebladdercancer(pioglitazone),cardiovascularcontroversy(rosiglitazone),6-12weeksrequiredformaximaleffect
$$
Weightlossagent(orlistat)
↓ None ↓ GIsideeffects $$$
alo=aloglip;n;glar=glargine;saxa=saxaglip;n;sita=sitaglip;n;lira=liraglu;de;lixi=lixisena;de;empa=empagliflozin 11/2016
Neutral (glar)
alo,saxa,sita:Neutral
Neutral
Empa:SuperiorityinT2DMpa;entswithclinicalCVD
Lira:superiorityinT2DMpa;entswithclinicalCVD
Lixi:neutral
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2016 Canadian Diabetes Association
Recommendation 4
4. In adults with type 2 diabetes with clinical cardiovascular disease in whom glycemic targets are not met, an antihyperglycemic agent with demonstrated cardiovascular outcome benefit should be added to reduce the risk of major cardiovascular events (Grade 1, Level 1A for empagliflozin ; Grade 1, Level 1A for liraglutide if age ≥50 years; Grade D, Consensus for liraglutide if age <50 years).
11/2016
22
GLP-1 receptor agonist
DAILY AGENTS WEEKLY AGENTS
Parameter Exenatide BID LIxisenatide Liraglutide Albiglutide Dulaglutide Exenatide
QW
Half-life 2.4 hrs ~3 hrs 13 hrs ~5 days ~5 days 7–14 days
Time to steady state
N/D N/D 3–5 days 4–5 weeks 2–4 weeks 6–7 weeks
A1C reduction -0.4 to -1.4% -0.7 to -0.9% -0.8 to -1.5% -0.6 to -0.8% -0.8 to -1.6% -1.3 to -1.9%
FPG reduction + + ++ + ++ ++
PPG excursion reduction
++ ++ + + + +
Gastric emptying
All GLP-1RAs slow gastric emptying, but less tachyphylaxis with EXE BID and LIXI
Body weight change (kg)
-0.9 to -2.8 -0.2 to -2.8
-1.6 to -3.2
+0.3 to -1.2 +0.2 to -3.0 -2.0 to -3.7
Nausea 33–57% 20–40% 10–47% 5–13% 8–28% 9–26%
Vomiting 12–17% 7–18% 4–17% 3–6% 4–17% 4–11%
GLP-1 Receptor Agonists
+ = modest reduction; ++ = strong reduction
GLP-1 receptor agonist CV Safety Trials Currently In Progress
2012 2013 2014 2015 2016 2017 2018 2019 2020
EXSCEL Exenatide QW vs.
Placebo N=14,000
REWIND Dulaglutide vs.
Placebo N=9,622
HARMONY Outcomes Albiglutide vs.
Placebo N=9,400
All are large, non-inferiority,
event driven CV safety studies on individuals with T2DM who are at high baseline CV
risk
25
EXSCEL, Exenatide Study of Cardiovascular Event Lowering Trial; HARMONY Outcomes, Effect of Albiglutide, When Added to Standard Blood Glucose Lowering Therapies, on Major Cardiovascular Events in Subjects With Type 2 Diabetes Mellitus; REWIND, Researching Cardiovascular Events With a Weekly Incretin in Diabetes.
• Prefilled single-dose pen
• Does not require reconstitution
• Injection steps (uncap, unlock, inject)
• Built-in needle (29g, 5mm)
Data on file. Eli Lilly and Company.
Dulaglutide Pen
26
• Prefilled single-dose pen
• Requires reconstitution
• Injection steps (attach needle, turn knob to click, tap against palm 80 times or more, turn knob again, inject)
• Separate needle (23 g, 7 mm)
Bydureon® US Prescribing Information. AstraZeneca. Available at: http://www.bydureonhcp.com Accessed September 16, 2014.
Exenatide QW Pen
27
Wysham C et al. Diabetes Care 2014;37:2159-67. Dungan KM et al. Lancet 2014;384:1349-1357. Drucker D et al. Lancet 2008;372:1240-50. Buse J et al. Lancet 2013;381:117-24. Pratley R et al. Lancet Diabetes Endocrinol 2014;2:289-97.
BL: baseline; MET: metformin; PIO: pioglitazone; DULA: dulaglutide; LIRA: liraglutide; EXE BID: exenatide twice daily; EXE QW: exenatide once weekly; ALBI: albiglutide
0.0
-0.2
-0.4
-0.6
-0.8
-1.0
-1.2
-1.4
-1.6
Cha
nge
in A
1C fr
om b
asel
ine
(%)
-1.8 -2.0
*Significant difference vs. comparator
Add-on to MET + PIO
AWARD-1** BL~8.1%
Add-on to MET
AWARD-6 BL~8.1%
Noninferior
-1.3 26
-1.0
EXE
BID
-1.5 28
-1.5*
DU
LA 1
.5
0.04* 16*
-1.3*
DU
LA 0
.75
-3.6 18
-1.4 LI
RA
1.8
-2.9* 20
-1.4
DU
LA 1
.5
Add-on to Diet or Orals
DURATION-1 BL~8.3%
Not noninferior
Add-on to MET ± SU or MET + PIO
DURATION-6 BL~8.5%
-3.6 21
-1.5
LIR
A 1.
8
-3.6 35
-1.5
EXE
BID
-3.7 26
-1.9* EX
E Q
W
-2.7* 9
-1.3*
EXE
QW
Add-on to OADs
HARMONY-7 BL~8.2%
Not noninferior
-1.0
LIR
A 1.
8
-2.2 29
-0.8*
-0.6* 10*
ALB
I† 50
CAUTION: Cross-trial comparisons cannot be made due to differences in study designs, trial durations and patient populations.
GLP-1RAs: Head-to-Head Trials of Once-Weekly vs. Daily Administration
Wt. Δ (kg): Nausea (%):
28
** The combination of DULA + MET + PIO is currently not an approved indication in Canada; †Approved but not yet marketed in Canada.
Insulin
3 types of insulin BASAL • NPH
• Lantus (glargine 100 u/mL) • Levemir (detemir)
• Basaglar (glargine 100 u/mL) • Toujeo (glargine 300 u/mL)
PRE-MIXED § 30/70
§ Humalog Mix25, Mix50 (insulin lispro/lispro protamine)
§ Novomix 30 (biphasic insulin aspart)
BOLUS • Regular or Toronto • Apidra (glulisine) • Humalog (lispro)
• Humalog 200 u/mL (lispro) • Novorapid (aspart)
• Fiasp (faster aspart)
3 types of insulin BASAL • NPH
• Lantus (glargine 100 u/mL) • Levemir (detemir)
• Basaglar (glargine 100 u/mL) • Toujeo (glargine 300 u/mL)
PRE-MIXED § 30/70
§ Humalog Mix25, Mix50 (insulin lispro/lispro protamine)
§ Novomix 30 (biphasic insulin aspart)
BOLUS • Regular or Toronto • Apidra (glulisine) • Humalog (lispro)
• Humalog 200 u/mL (lispro) • Novorapid (aspart)
• Fiasp (faster aspart)
McMahon GT, Dluhy RG. NEJM 2007;357:1759.
0 12 24
Rel
ativ
e G
lyce
mic
Effe
ct
Duration in Hours
NPH
Detemir
Glargine
3 types of insulin BASAL • NPH
• Lantus (glargine 100 u/mL) • Levemir (detemir)
• Basaglar (glargine 100 u/mL) • Toujeo (glargine 300 u/mL)
PRE-MIXED § 30/70
§ Humalog Mix25, Mix50 (insulin lispro/lispro protamine)
§ Novomix 30 (biphasic insulin aspart)
BOLUS • Regular or Toronto • Apidra (glulisine) • Humalog (lispro)
• Humalog 200 u/mL (lispro) • Novorapid (aspart)
• Fiasp (faster aspart)
NS=not significant Rosenstock et al. Diab Obes Metab 2015; 17:734-41.
*Gla-100=referenceglargine100u/mLSEBglar=subsequententrybiologicglargine
-1.34 -1.54 -1.01-1.29 -1.48 -1.02
-2
-1.5
-1
-0.5
0Total Insulin-naïve PriorIGlar
Gla-100 (N=268) SEB glar (N=267)
∆ = -0.004 95% CI (-0.19, 0.19)
p=NS ∆ = 0.061
95% CI (-0.09, 0.21) p=NS
∆ = 0.052 95% CI (-0.07, 0.18)
p=NS
ChangeinHbA
1c(%
)
Consistent A1C change for SEB glargine vs reference Gla-100 at Month 6 in T2DM
No difference in hypoglycemia since both are Gla-100
http://guidelines.diabetes.ca/browse/appendices/appendix5_2016
3 types of insulin BASAL • NPH
• Lantus (glargine 100 u/mL) • Levemir (detemir)
• Basaglar (glargine 100 u/mL) • Toujeo (glargine 300 u/mL)
PRE-MIXED § 30/70
§ Humalog Mix25, Mix50 (insulin lispro/lispro protamine)
§ Novomix 30 (biphasic insulin aspart)
BOLUS • Regular or Toronto • Apidra (glulisine) • Humalog (lispro)
• Humalog 200 u/mL (lispro) • Novorapid (aspart)
• Fiasp (faster aspart)
Time,h
3
2
1
0
140
120100
160
0 6 12 18 24 30 36
Glargine300U/mL:1/3theVolumeMoreconstantandprolongedPK/PD
U3000.4U/kgU1000.4U/kg
0 6 12 18 24 30 36
Glucoseinfusionrate,mg/kg/min
Bloodglucose,mg/dL
BeckerRHAetal.DiabetesCare.2014;Publishedaheadofprint:doi:10.2337/dc14-0006
Euglycemicclampstudyinpa;entswithT1Daper8days’treatment
37
PD,pharmacodynamic;PK,pharmacokine;c
Reduc8onofvolumeby2/3
100 U/mL (U100)
300 U/mL (U300)
300 U/mL (U300)
100 U/mL (U100)
Reduc8onofdepotsurfaceby1/2
3 types of insulin BASAL • NPH
• Lantus (glargine 100 u/mL) • Levemir (detemir)
• Basaglar (glargine 100 u/mL) • Toujeo (glargine 300 u/mL)
PRE-MIXED § 30/70
§ Humalog Mix25, Mix50 (insulin lispro/lispro protamine)
§ Novomix 30 (biphasic insulin aspart)
BOLUS • Regular or Toronto • Apidra (glulisine) • Humalog (lispro)
• Humalog 200 u/mL (lispro) • Novorapid (aspart)
• Fiasp (faster aspart)
McMahon GT, Dluhy RG. NEJM 2007;357:1759.
0 12 24
Rel
ativ
e G
lyce
mic
Effe
ct
Duration in Hours
Human Regular
Aspart Glulisine Lispro
3 types of insulin BASAL • NPH
• Lantus (glargine 100 u/mL) • Levemir (detemir)
• Basaglar (glargine 100 u/mL) • Toujeo (glargine 300 u/mL)
PRE-MIXED § 30/70
§ Humalog Mix25, Mix50 (insulin lispro/lispro protamine)
§ Novomix 30 (biphasic insulin aspart)
BOLUS • Regular or Toronto • Apidra (glulisine) • Humalog (lispro)
• Humalog 200 u/mL (lispro) • Novorapid (aspart)
• Fiasp (faster aspart)
3 types of insulin BASAL • NPH
• Lantus (glargine 100 u/mL) • Levemir (detemir)
• Basaglar (glargine 100 u/mL) • Toujeo (glargine 300 u/mL)
PRE-MIXED § 30/70
§ Humalog Mix25, Mix50 (insulin lispro/lispro protamine)
§ Novomix 30 (biphasic insulin aspart)
BOLUS • Regular or Toronto • Apidra (glulisine) • Humalog (lispro)
• Humalog 200 u/mL (lispro) • Novorapid (aspart)
• Fiasp (faster aspart)
Faster aspart vs insulin aspart: Faster onset of exposure and faster absorption
IAsp
Faster aspart
Heise T et al. Diabetes, Obesity and Metabolism 2015; 17:682–688.
Thr Lys
Thr Tyr Phe Phe
Gly Arg
Glu Gly Cys Val Leu Tyr Leu Ala Glu Val
Leu His
Ser Gly
Cys Leu His Gln Asn Val Phe
Gly Ile Val Glu
Gln Cys Thr Ser Ile Cys Ser
Leu Tyr Gln Leu Glu
Asn Tyr
Cys Asn
Cys
B30
B28
A21
A1
B1
Asp
Nicotinamide
O NH2 N L-arginine
N H
H2N
NH
NH2
O
OH
• Inject up to 2 minutes before the meal OR up to 20 minutes after the meal
3 types of insulin BASAL • NPH
• Lantus (glargine 100 u/mL) • Levemir (detemir)
• Basaglar (glargine 100 u/mL) • Toujeo (glargine 300 u/mL)
PRE-MIXED § 30/70
§ Humalog Mix25, Mix50 (insulin lispro/lispro protamine)
§ Novomix 30 (biphasic insulin aspart)
BOLUS • Regular or Toronto • Apidra (glulisine) • Humalog (lispro)
• Humalog 200 u/mL (lispro) • Novorapid (aspart)
• Fiasp (faster aspart)
Hotoffthepress!
44
FDADrugSafetyCommunica;onsMay16,2017
NNH = 323 in 1yr
NNH = 270 in 1yr
47
What should we do?
• Do NOT use in type 1 diabetes
• Remember EUGLYCEMIC diabetic ketoacidosis is a rare possibility
• Be cautious with insulin dose reductions in “insulin deficient” pt
• Be cautious in acute illness / surgery
• Do not routinely check for ketonuria
S - sulfonylurea
A – ACE-inhibitor
D – diuretic, DRI
M - metformin
A - ARB
N - NSAIDs
S – SGLT2 inhibitors
Keeping it simple …
Insulin All options available
COULD THE PATIENT BE INSULIN DEFICIENT?
• Lower BMI • Lack of glycemic
lowering with other meds • Duration of T2DM
(sometimes)
• Higher BMI • Shorter duration of
T2DM (sometimes)
Boiling it down …
1. Does this patient have clinical cardiovascular disease? à empa or lira
2. How high are the sugars? 3. Is he/she at risk of hypoglycemia? 4. What is the eGFR? 5. Is there a drug plan?
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association
Add another agent best suited to the individual by prioritizing patient characteristics:
Degree of hyperglycemia Risk of hypoglycemia Overweight or obesity CV disease or multiple risk factors Comorbidities (renal, CHF, hepatic) Preferences & access to treatment
Consider relative A1C lowering Rare hypoglycemia Weight loss or weight neutral Effect on cardiovascular outcome See therapeutic considerations See cost column; consider access
PATIENT CHARACTERISTIC CHOICE OF AGENT
PRIORITY: Clinical Cardiovascular Disease
Antihyperglycemic agent with demonstrated CV outcome benefit (empagliflozin, liraglutide)
2016
Addanotherclassofagentbestsuitedtotheindividual(agentslistedinalphabe.calorder):
Class Rela8veA1CLowering
Hypo-glycemia
Weight EffectinCardiovascularOutcomeTrial
Othertherapeu8cconsidera8ons Cost
α-glucosidaseinhibitor(acarbose)
↓ Rare Neutralto↓
Improvedpostprandialcontrol,GIside-effects $$
DPP-4Inhibitors ↓↓
Rare
Neutralto↓
alo,saxa,sita:
Neutral
Cau;onwithsaxaglip;ninheartfailure
$$$
GLP-1Ragonists ↓↓to↓↓↓ Rare ↓↓
lira:SuperiorityinT2DMpa;entswithclinicalCVD
lixi:Neutral
GIside-effects
$$$$
Insulin ↓↓↓ Yes ↑↑ Neutral(glar) Nodoseceiling,flexibleregimens $-$$$$
Insulinsecretagogue:Megli;nideSulfonylurea
↓↓↓↓
YesYes
↑↑
LesshypoglycemiaincontextofmissedmealsbutusuallyrequiresTIDtoQIDdosingGliclazideandglimepirideassociatedwithlesshypoglycemiathanglyburide
$$$
SGLT2inhibitors ↓↓to↓↓↓
Rare ↓↓
empa:SuperiorityinT2DMpa;entswithclinicalCVD
Genitalinfec;ons,UTI,hypotension,dose-relatedchangesinLDL-C,cau;onwithrenaldysfunc;onandloopdiure;cs,dapagliflozinnottobeusedifbladdercancer,rarediabe;cketoacidosis(mayoccurwithnohyperglycemia)
$$$
Thiazolidinediones ↓↓ Rare ↑↑ Neutral CHF,edema,fractures,rarebladdercancer(pioglitazone),cardiovascularcontroversy(rosiglitazone),6-12weeksrequiredformaximaleffect
$$
Weightlossagent(orlistat)
↓ None ↓ GIsideeffects $$$
alo=aloglip;n;glar=glargine;saxa=saxaglip;n;sita=sitaglip;n;lira=liraglu;de;lixi=lixisena;de;empa=empagliflozin 11/2016
Antihyperglycemic Agents and Renal Function
* do not initiate if eGFR <60 ml/min ** Davies ML et al. Diabetes Care 2016;DOI:10.2337/dc14-2883. Adapted from: Product Monographs as of March 2016. Harper W et al. Can J Diabetes 2015;39:440
eGFR(mL/min/1.73m2): <15 15–29 30–59 60–89 ≥90CKDStage: 5 4 3 2 1
Acarbose Notrecommended 25
Dapagliflozin 60Empagliflozin 45
Thiazolidinediones 30Contraindicated SafeCau8onand/ordose
reduc8on
Canagliflozin 25 60*100mg45
60*10or25mg
Nodoseadjustmentbutclosemonitoringofrenalfunc8on
Notrecommended
MeWormin 30 60
15Linaglip;n
Sitaglip;n 5030 50mg25mg
Saxaglip;n 5015 2.5mg
Aloglip;n Notrecommended 506.25mg 12.5mg30
Exena;de(BID/QW) 30 50Liraglu;de** 50
Albiglu;de 50
30
Repaglinide
Gliclazide/Glimepiride 15 30Glyburide 30 50
Insulin Secreta-gogues
SGLT2 inhibitors
GLP-1R agonists
Alpha-glucosidase
Inh. Biguanide
DPP-4 inhibitors
Dulaglu;de 50
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association
Guidelines.diabetes.ca
guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association
Summary
• Remember pathophysiology • Metformin still top dog • Cardiovascular disease priority
individualization – empa or lira • Use the tools available to you:
www.guidelines.diabetes.ca
Twitter: @AliceYYCheng