Transcript Practical Implementation as a Discussion with the Patient, Part 2

Practical Implementation as a
Discussion with the Patient, Part 2
Practical Use of SGLT-2 Inhibitors in T2DM:
Clinical Pearls- Perlas de Sabiduria
Stan Schwartz MD, FACP
Affiliate, Main Line Health System
Emeritus, Clinical Associate Professor of Medicine,
U of Pa.
[email protected]
PEARL:
Match Patient characteristics to Drug
Characteristics and Vice Versa
AACE/ACE: Recommendations Based on A1C
Lifestyle Modifications
A1C 6.5%-7.5%
A1C 7.6%-9.0%
If under
treatment
Monotherapy
Dual therapy
Insulin plus
other
agent(s)*
Dual therapy
Triple therapy
*
Triple therapy
A1C > 9.0%
Triple therapy
If drug
naive
Insulin plus
other
agent(s)*
PEARL
Not first ,second, third line;
not competition between classes;
It’s early combination therapy
Rodbard HW, et al. Endocr Pract. 2009;15:540-559.
Glucose
(mg/dl)
Relative -cell
Function (%)
Incretins* (GLP-1 RA, DPP-4 Inh.)
SGLT-2 Inhibitors *with caution re:Immune Sup. Levels
Nutrition
Exercise,
NO SMOKING
Onset of Diabetes
Postmeal Glucose
Fasting
Glucose
Insulin-Resistance
250
200
150
Insulin Level
Insulin
Insulin
100
-10
PICK RIGHT
DRUG FOR
RIGHT PT.
Insulin
350
300
250
200
150
100
50
50
0
Combo
therapy-in
AACE >7.5
TZD (Pioglitazone), metformin, bromocriptine QR
.
• Consider therapy
for prevention (future)
• Early treatment,
even with IGT
• FAST
THERAPEUTIC
CHANGES
• Not 1st,2nd ,3rd line;
• not competition betw.
classes;
early combo therapy
-5
-0
5
10
15
20
25
-Delay Need
for Insulin
-No need for
Early Insulin
-If need
Insulin,
Continue NonInsulin RX
(Avoids need
for Meal-Time
InsulinDecrease Risk
Hypoglycemia
85%- Get
Patients off
insulin
Who had been
given early
Insulin
30
Rx PRINCIPLES-Uses Across Continuum of Care
Modified from Bergenstal RM, International Diabetes Center.
Logic for
SGLT-2 Inhibition:
My Own Comment on MOALogic 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?
Likely No Undue Risk to Kidney
Familial Renal Glucosuria
Presentation
• Glucosuria: 1-170 g/day
• Asymptomatic
Blood
• Normal glucose concentration
• No hypoglycemia or hypovolemia
Kidney / bladder
• No tubular dysfunction
• Normal histology and function
Complications
• 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
• Decrease glucose;
Decrease BP;
• Decrease Hyperfiltration;
Decrease weight
Decrease microalbuminuria
Canagliflozin (SGLT-2 Inhibitors do it All)
david.cherneyCurr Opin Nephrol Hypertens 2015, 24:96–103
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 benefit
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.
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 proactive 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
• Changes in fasting lipids
–Increases in LDL-C
–Increases in HDL-C
–Minimal change in LDL-C/HDL-C ratio
–Decreases in TG
Smaller 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
• 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
• As Write Initial Script
– Teach Volume Issues
 Keep Urine Dilute (let kidney tell patient if they’re drinking
‘enough’)
– UTI/ Yeast Infection Issues
 Make 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