practical implementation as a discussion with the patient, part 2 practical use of sglt-2 inhibitors...
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Practical Implementation as a Discussion with the Patient, Part 2
Practical Use of SGLT-2 Inhibitors in T2DM:
Clinical Pearls- Perlas de SabiduriaClinical Pearls- Perlas de Sabiduria
Stan Schwartz MD, FACPAffiliate, Main Line Health System
Emeritus, Clinical Associate Professor of Medicine, U of Pa.
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PEARL:Match Patient characteristics to Drug
Characteristics and Vice VersaAACE/ACE: Recommendations Based on A1C
Rodbard HW, et al. Endocr Pract. 2009;15:540-559.
A1C 6.5%-7.5% A1C 7.6%-9.0% A1C > 9.0%If undertreatment
If drugnaive
Insulin plusother
agent(s)*Insulin plus
other agent(s)*
Symptom
s
No
sym
ptom
s
Lifestyle Modifications
*
Monotherapy
Dual therapy
Triple therapy
Dual therapy
Triple therapy
Triple therapy
PEARLNot first ,second, third line;
not competition between classes;It’s early combination therapy
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350300250200150100
50
250
200
150
100
50
0
Insulin-Resistance
Rel
ativ
e -
cell
Fun
ctio
n (%
)
Insulin Level
FastingGlucose
Glu
cose
(m
g/dl
)
Onset of Diabetes
Postmeal Glucose
Incretins* (GLP-1 RA, DPP-4 Inh.)
Insulin
TZD (Pioglitazone), metformin, bromocriptine QR
Insulin
-10 -5 -0 5 10 15 20 25 30
Insulin
Modified from Bergenstal RM, International Diabetes Center.Rx PRINCIPLES-Rx PRINCIPLES-Uses Across Continuum of Care
• Consider therapyfor prevention (future)
• Early treatment,even with IGT
• FASTTHERAPEUTICCHANGES
• Not 1st,2nd ,3rd line;• not competition betw.
classes;
early combo therapy
-Delay Need for Insulin-No need for Early Insulin-If need Insulin, Continue Non-Insulin RX(Avoids need for Meal-Time Insulin- Decrease Risk Hypoglycemia 85%- Get Patients off insulin Who had been given early Insulin
Combo therapy-inAACE >7.5
PICK RIGHT DRUG FOR RIGHT PT.
Nutrition Exercise, NO SMOKING
.SGLT-2 Inhibitors *with caution re:Immune Sup. Levels
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Logic for SGLT-2 Inhibition:
Logic for SGLT-2 Inhibition:
My Own Comment on MOA- Logic for Benefit:
1.Kidney is an ‘active player’ in Hyperglycemia--2.EARLY (in pre-diabetes) Up-regulation of SGLT-2 protein is a Mal-adaptive response to body perceiving lose of glucose as a risk for insufficient glucose for brain function
3.Lowering blood sugar by reducing tubular re-absorption of glucose treats THE Core defect in Diabetes- abnormal b-cell function, by decreasing glucotoxicity, AND, by virtue of weight loss, improves Insulin Resistance
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But Won’t Sugar Hurt My Kidneys?But Won’t Sugar Hurt My Kidneys?
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Likely No Undue Risk to KidneyFamilial Renal GlucosuriaLikely No Undue Risk to KidneyFamilial Renal Glucosuria
PresentationPresentation• Glucosuria: 1-170 g/dayGlucosuria: 1-170 g/day
• AsymptomaticAsymptomatic
BloodBlood• Normal glucose concentration
• No hypoglycemia or hypovolemiaNo hypoglycemia or hypovolemia
Kidney / bladderKidney / bladder• No tubular dysfunction
• Normal histology and function
ComplicationsComplications
• No increased incidence of
– Chronic kidney disease
– Diabetes
– Urinary tract infection
Santer R, et al. J Am Soc Nephrol. 2003;14:2873-2882;Wright EM, et al. J Intern Med. 2007;261:32-43.
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Likely Benefit, Not Harm, to Kidneys Over Time:if Wanted to Protect Kidney in DM, one would want
Likely Benefit, Not Harm, to Kidneys Over Time:if Wanted to Protect Kidney in DM, one would want
• Decrease glucose; Decrease BP; Decrease weight
• Decrease Hyperfiltration; Decrease microalbuminuria
Canagliflozin (SGLT-2 Inhibitors do it All)
david.cherneyCurr Opin Nephrol Hypertens 2015, 24:96–103DOI:10.1097/MNH.0000000000000084
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Therapeutic Logic of SGLT-2 Inhibitors to Fulfill Unmet Needs; Can Tell Patient :
Therapeutic Logic of SGLT-2 Inhibitors to Fulfill Unmet Needs; Can Tell Patient :
• Effective Glycemic Control with No undue risk for hypoglycemia (unless combined with
Insulin or Insulin Secretagogue Therapy) Durable- (2 yr data)
• Reduces HgA1c, Fasting and Postprandial Hyperglycemia1,
• Decreases variability, (related to increased risk of DM complications)
• Additive benefits with incretins, esp. GLP-RA’s
• Delay, prevent need for insulin;
• delay, prevent need for fast-analog insulin in T2DM (thus decrease potential hypo-with insulin Rx (85% reduction if avoid fast-analogs)
• Works with FIRST DOSE- patients love to see QUICK benefit1. Blonde L. Am J Manag Care. 2007;13(suppl 2):S36-S40. 2.Blonde L, et al. J Manag Care Pharm. 2006;12(7 suppl A):S2-S12.
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Therapeutic Logic of SGLT-2 Inhibitors to Fulfill Unmet Needs; I’ve seen:
Therapeutic Logic of SGLT-2 Inhibitors to Fulfill Unmet Needs; I’ve seen:
• Minimal GI side effects (only with volume depletion)
• No edema, in fact, decreases modest existing edema;decreases/obviates edema of pioglitazone
• Acceptable side effect profile that can be minimized by quality pro-active care- volume depletion, UTI, yeast infections
1. Blonde L. Am J Manag Care. 2007;13(suppl 2):S36-S40. 2.Blonde L, et al. J Manag Care Pharm. 2006;12(7 suppl A):S2-S12. GI: gastrointestinal.
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CV Risk Factor Changes with SGLT-2 Inhibitors- Can Reassure Patient
CV Risk Factor Changes with SGLT-2 Inhibitors- Can Reassure Patient
• Changes in fasting lipids
–Increases in LDL-C–Increases in HDL-C–Minimal change in LDL-C/HDL-C ratio–Decreases in TGSmaller increases in non-HDL-C, Apo B, LDL particle number
• Decreases in systolic and diastolic blood pressure
• Improved glycemic control
• Decrease in body weight
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Practical Clinical Approaches To Maximize Benefits and Minimize Risks
Practical Clinical Approaches To Maximize Benefits and Minimize Risks
• As Write Initial Script–Check eGFR, BUN/Cr,
eGFR appropriate dosing
lower doses for lower eGFR, older, on loop-diuretic;
Advise push PO fluids, hold med with a GI flu, sweaty exercise etc;
Note to patient increased urination expected=
12-14oz/d early, later ~6 oz/d
– Check K- if K+ high nml- adjust K=sparing diuretic,ACE/ARB
decrease high K+ foods
– Check BP- if Low BP- cut back/stop something- HCTZ, spironolactone, or BP med- ACE inh.
– Check Recent Sugars- Very High sugar- start other meds
and NCS diet first, start SGLT-2 3 days later
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Practical Clinical Approaches To Maximize Benefits and Minimize Risks
Practical Clinical Approaches To Maximize Benefits and Minimize Risks
• As Write Initial Script– Teach Volume Issues
Keep Urine Dilute (let kidney tell patient if they’re drinking
‘enough’)
– UTI/ Yeast Infection IssuesMake sure ho history frequent issues in past- if so, don’t use
Female- careful bathroom habits, urinate after intercourse before sleep
Male- especially uncircumsized- get tip of penis dry before leave bathroom