Practical Implementation as a Discussion with the Patient, Part 2 Practical Use of SGLT-2 Inhibitors...
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Transcript of Practical Implementation as a Discussion with the Patient, Part 2 Practical Use of SGLT-2 Inhibitors...
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.
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
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
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
But Won’t Sugar Hurt My Kidneys?But Won’t Sugar Hurt My Kidneys?
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.
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
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.
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.
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
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
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