CASE STUDIES IN DIABETES: PRACTICAL POINTERS FOR … · cNot FDA-approved for weight...
Transcript of CASE STUDIES IN DIABETES: PRACTICAL POINTERS FOR … · cNot FDA-approved for weight...
CASE STUDIES IN DIABETES: Practical Pointers for
Evidenced Based Practice
Debbie Hinnen APN, BC-ADM, CDE, FAANUniversity of Colorado Health- Colorado Springs
Let’s think through some things
• 56 y/o Hispanic male• Type 2 diabetes• 2 years on Metformin 1,000 mg BID• A1c increasing to 8.9% over past year• Further attempts at lifestyle change unsuccessful
Case 1
Virginia Valentine APRN-CNS, BC-ADM, CDE, FAADE
Case 1More background info:
Electric co. lineman
Well insured
Copays $10-40
100% office visit attendance
Declines injectables
HTN, on lisinopril,
Hyperlipidemia rosuvastatin
Father CAD
Objective findings:
Obese, BMI 36.5
BP 142/84
Acanthosis nigricans
ECG: normal
A1c 8.9%, FPG 177
Cr 1.1 (eGFR >60)
LDL 84, HDL 38, TG 256
Case Worksheet• Set goals:
• A1c• Glucose goals• Lipid goals
• Priorities• Patient preferences• Cost/Formulary
• Initiation and Follow up• SMBG/CGM-Frequency of contact• Adverse events• other
Treatment Recommendations Specify Multiple Individualized Goals for Patients With T2DM
Weight loss: ≥ 5%For overweight or obese patients, based on achievement of individualized health goals1,2
A1C: < 7.0%1 or ≤ 6.5%2
More stringent for some (eg, < 6.5%), if safely achieveable1,2
Higher (eg, < 8.0%) may be appropriate for others1,2
BP: < 140/901 mm Hg or < 130/802 mm HgLower targets (eg, < 130/80 mm Hg) may be appropriate for patients at high risk of CVD, if achievable without undue treatment burden1
Statin therapy according to CVD risk1,2
LDL-C based on CVD risk2
- High risk: < 100 mg/dL- Very high risk: < 70 mg/dL- Extreme risk: < 55 mg/dL
1. . Garber AJ, et al. Endocr Pract. 2017;23:207-238.
ADA: Standards of Medical Carein Diabetes – 2019 Diabetes Care
January 2019, 42 Suppl 1 S90-S102
ADA: Standards of Medical Carein Diabetes – 2019 Diabetes Care
January 2019, 42 Suppl 1 S90-S102
ADA: Standards of Medical Carein Diabetes – 2019 Diabetes Care
January 2019, 42 Suppl 1 S90-S102
Education Point: Complementary Agents Address Different Aspects of Disease Pathophysiology1-3,a
a Commonly used agents according to ADA guidelines.
1. ADA. Diabetes Care. 2017;40(suppl 1):S1-S135. 2. Garber AJ, et al. Endocr Pract. 2017;23:207-238.
3. Inzucchi SE, et al. Diabetes Care. 2015;38:140-149.
Insulin:• Insulin (exogenous) • SU• GLP-1 RA, DPP-4i
(glucose dependent)Glucagon:• GLP-1 RA, DPP-4i
(glucose dependent)
Hepatic glucose:• Metformin,
insulin
Insulin sensitivity:• TZD
Satiety:• GLP-1 RA
Glucose reabsorption:• SGLT2i
Formulary Look Up Tools
• MMIT• https://formularylookup.com/
• Finger tip formulary• https://lookup.decisionresourcesgroup.com/
• TriCare – Express Scripts• https://www.express-
scripts.com/static/formularySearch/2.9.2/#/formularySearch/drugSearch• Retail cost of drugs GoodRx
• https://goodrx.com
Case Worksheet• Set goals:
• A1c: 6.5-7%• Glucose goals: Fasting 80-110, After meals <140mg• Lipid goals: ~70 or 30% lower than baseline
• Priorities• Patient preferences: No Injections• Cost/Formulary: reasonable co-pays
• Initiation and Follow up: Add low dose SGLT2 on formulary or GLP• SMBG/CGM-Frequency of contact: 4x/d 2 days/week. Call/fax BG
1-2 weeks. F/U 3 months. A1C• Adverse events: GMI, UTI• Other: drink extra 12 oz water/day. Good hygiene. Stop if not
eating/drinking, procedures.
SGLT2 Inhibitors Improve Glycemic Control When Added to Metformin Monotherapy
-0.8
-0.5-0.6
-1.0
-0.8
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-0.4
-0.2
0.0
PBO
-sub
trac
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%
Δ A1C1,a
a Data do not represent head-to-head comparisons; similar duration ( 6 months) and baseline values across trials.
1. US FDA. Drugs@FDA. http://www.accessdata.fda.gov/scripts/cder/daf/.2. Rosenstock J, et al. Diabetes Care. 2015;38:376-383.
3. Forst T, et al. Diabetes Obes Metab. 2016 Dec 23. [Epub ahead of print].
58%, 41%, and 39% of patients achieved A1C < 7%, respectively1
CANA (300 mg) DAPA (10 mg) EMPA (25 mg)
-40
-18
-29
-75
-50
-25
0
PBO
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trac
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mg/
dL
Δ FPG1,a
-50
-70-75
-50
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BL-s
ubtr
acte
d, m
g/dL
Δ 2-h PPG1,2,a
All significant vs PBO
All significant vs PBO
EMPA also decreases PPG when added to MET monotherapy3
Be a Hero, GGo the extra mile for your patients
Case 264 y/o FemaleType 2 diabetes for 14 yrs on Metformin 1,000 BID and Sitagliptin 100 mg dailyRecently hospitalized for ACS / stentDiastolic dysfunction by echoPrior A1C’s stable at 7-7.5%A1C currently at 8.4%Cardiologist told her to seek your counsel about improving metabolic control
Case 2
More background info:
Grade school teacherWell insuredNo copaysCAD s/p MI; HTN, hypothyroid, breast caAtorvastatin, quinapril, tamoxifen, ASAOpen to injections
Objective findings:
Obese, BMI 32.1
BP 118/76
ECG: old MI
A1c 8.4%, FPG 188
Cr 1.4 (eGFR 44)
LDL 67, HDL 54, TG 123
Case Worksheet• Set goals:
• A1c• Glucose goals• Lipid goals
• Priorities• Patient preferences• Cost/Formulary
• Initiation and Follow up• SMBG/CGM-Frequency of contact• Adverse events• other
A1C 7%
Glycemic Targets Should be Individualized
ADA. Diabetes Care. 2017;40(suppl 1):S1-S135.
Risks associated with hypoglycemia or other drug
adverse effects
Newly diagnosedDisease duration
Long ShortLife expectancy
Low High
Important comorbidities
Highly motivated, adherent, excellent self-care capabilities
Frequent
Established vascular complications
Readily available Limited
Patient attitude/expected treatment efforts
Resources and support system
Long-standing
Absent SevereFew/mild
Absent SevereFew/mild
Less motivated, nonadherent, poor self-care capabilities
Usually not modifiable
Potentiallymodifiable
More stringent Less stringent Hazard ratio (95% CI)
CANVAS Program EMPA-REG OUTCOME 1.00.5 2.0
Favors PlaceboFavors SGLT2i
Nonfatal myocardial infarction
Progression to macroalbuminuria*
Renal composite*
Hospitalization for heart failure
CV death, nonfatal myocardial infarction, or nonfatal stroke
CV death
Nonfatal stroke
Key Outcomes in the CCANVAS Program and EMPA-REG OUTCOME
*CANVAS Program endpoints comparable with EMPA-REG OUTCOME.
0.25
Zinman Bet al. N Engl J Med. 2015 ;373(22):2117-2128.Wanner K et al. N Engl J Med. 2016;375(4):323-334.Neal et al N Eng J Med. 2017. Published June 12. doi:10.1056/NEJMoa1611925
c Not FDA-approved for weight loss. Zaccardi F, et al. Diabetes Obes Metab. 2016;18:783-794.
Effects of SGLT2 Inhibitors on CV Risk Factors
CANA 300 mg CANA 100 mg DAPA 10 mg DAPA 5 mg EMPA 25 mg EMPA 10 mg
-2.5
-1.9-2.2
-1.6
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-1
0Weight Change
Mea
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ange
vs P
BO,
kg
c
P < .05 for all vs PBO
-4.9-3.9
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0SBP Change
Mea
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vs P
BO, m
m
Hg
P < .05 for all vs PBO
P < .05 for all DBP changes vs PBO (-1.5 to -2.0 mm Hg)
7.7
3.52.7
1.5 1.91.2
0
2
4
6
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10LDL-C Change
Mea
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vs P
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g/dL
Significant increase with CANA vs PBO and all treatment groups
Case 3• 67 year old Latino male• 8 year diagnosis of T2DM• Retired public high school teacher; MCare and Humana supplement• BMI 38.3kg/m• BP 142/92• A1C 8.9% Prior A1C’s 7-7.6%• Current DM Meds
• Pioglitazone/metformin XR 15mg/1000 bid• Glimiperide 4mg
Case 3• More Background Info• - Routine DM visit• -Widowed, 2 adult children• DM meds:
• Pioglitazone/Metformin XR 15/1000 bid• Glimepiride 4mg/d
• Other meds:• HCTZ 25mg• Metoprolol 50mg• Simvastatin 20mg• ASA 81mg
• Uses a pill organizer
• Objective Data• -Thyroid – WNL• -Foot exam – WNL
• +pedal pulses, + reflexes,+ vibratory and monofilament
• Labs:• -FPG 135mg• Lipids
• LDL 95mg/dl• HDL 43 mg/dl• TG 197mg/dl
• LFT – WNL• GFR ->60• TSH WNL
Case Worksheet• Set goals:
• A1c• Glucose goals• Lipid goals
• Priorities• Patient preferences• Cost/Formulary, Use MMIT, finger tip formulary…..
• Initiation and Follow up• SMBG/CGM, Frequency of contact• Adverse events, patient education• Other
GLP-RAs vs SGLT2s (Invokana) 12 month A1Cs
a Meta-analysis of 34 studies of 14,464 participants, RCTs were 24-32 weeks long, background therapies of MET, SU, TZD, or insulin alone or in combination.b All P < .05 vs PBO.c Agents not approved for weight loss at doses indicated for diabetes management. Htike ZZ, et al. Diabetes Obes Metab. 2017;19:524-536.
Efficacy of GLP-1 RAs in Combination With Other Agentsa
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0.0A1C Change
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vs P
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bo, %
b
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lace
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g/dL
b
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cEXN BID LIXI LIRA EXN ER DULA
SGLT2 Label Precautions: Recommendations for Reducing Risks
a Assess blood ketones rather than urinary ketones.b Potential consequence of intravascular volume contraction.c Predisposing factors include pancreatic insulin deficiency, caloric restriction, alcohol abuse.
1. Drugs@FDA. http://www.accessdata.fda.gov/scripts/cder/daf/.2. Monami M, et al. Diabetes Res Clin Pract. 2017;130:53-60.
3. Handelsman Y, et al. Endocr Pract. 2016;22:753-762.
Elevated LDL-C1
Monitor, treat as appropriate
Lower limb amputation (eg, toe, mid-foot, leg below knee)1
2-fold risk increase with CANA, possibly higher risk with ERTU
Consider predisposing factors before starting (eg, prior amputation, PVD, neuropathy)
Counsel on routine foot care Renal injury1,b
Consider predisposing factors (eg, hypovolemia risk, CHF, medications)
Discontinue temporarily in cases of fluid loss/low fluid intake
Monitor – discontinue SGLT2i and treat if injury occurs
Hypotension1,b
Assess, correct volume status for individuals at higher risk (eg, elderly, with renal impairment, on diuretics)
Monitor
Ketoacidosis1-3
Low risk when properly prescribed2
Consider as a possible diagnosis, assessa if signs and symptoms, regardless of BG level,1,3 and treat if suspected1,3
To minimize risk• Stop before invasive procedures, stressful activity2
• Avoid excessively decreasing or stopping insulin3
• Consider predisposing factors before starting1,c
Case 4
• 79 year old African American man• Long standing T2DM ~ 20 years• Retired naval officer and postal worker. Insurance: TriCare for Life• Married, 3 adult children• Requested appt due to hypoglycemia• A1C 8.3%• Current DM meds
• Metformin XR 2000mg• Glimeperide 4mg• Insulin Levemir 15u bid
Case 4• More Background• DM meds:
• Metformin XR 2000mg/d• Glimepiride 6 mg/d• Levemir 15u bid
• Other meds:• HCTZ 25mg/d• Metoprolol 100mg/d• ASA 81mg
• Objective data• 73 in BMI 29• BP- 142/95• Thyroid –WNL• Foot exam: +/-monofilament -
Vibratory/+pedal pulses • A1C- 8.3%• Lipids- LDL 112, HDL 41, TG 205,
Total 194mg/dl• LFT- WNL• SrCr -1.6mg/dl GFR 49.7 ml/min
Case Worksheet• Set goals:
• A1c• Glucose goals• Lipid goals
• Priorities• Patient preferences• Cost/Formulary, Use MMIT, finger tip formulary…..
• Initiation and Follow up: Ultra long basal, meal time insulin, FRC Soliqua or Xultophy?• SMBG/CGM, Frequency of contact• Adverse events, patient education• Other
Clinical Characteristics of Basal Insulins vs U-100 Glargine in T2DM
U-100 NPH1 U-100 Detemir1 U-100 Glargine Equivalent2
U-300 Glargine3 U-100 Degludec4,5
Insulin dose =12% 4%
A1C = = = = =Weight =
0.77 kg=
0.28 kg=
Overall hypoglycemia = = =14% 19%
Nocturnal hypoglycemia = =Severe hypoglycemia = = = =
40%
Statistically significant differences indicated by arrows.
1. Rys P, et al. Acta Diabetol. 2015;52:649-662.2. Rosenstock J, et al. Diabetes Obes Metab. 2015;17:734-741;
3. Ritzel R, et al. Diabetes Obes Metab. 2015;17:859-867.4. Zhang XW, et al. Acta Diabetol. 2018 Feb 8. [Epub ahead of print].
5. Marso SP, et al. N Engl J Med. 2017;377:723-732.
See Resource section for more recommendations on SMBG and CGM use in T2DM.
1. Devices@FDA. https://www.accessdata.fda.gov/scripts/cdrh/devicesatfda/. 2. Fonseca VA, et al. Endocr Pract. 2016;22:1008-1021.
3. Peters AL, et al. J Clin Endocrinol Metab. 2016;101:3922-3937.4. Danne T, et al. Diabetes Care. 2017;40:1631-1640.
Blood Glucose MonitoringCGM Catches Glycemic Excursions that SMBG May Miss1
Some CGM Systems Can Replace SMBG1
As of February 2018, the following systems meet these criteria1:
Abbott FreeStyle Libre Flash Dexcom G5 Mobile CGMxcom G5 Mobile CGM
Case 5 Gestational DM
• 23 y/o G2 P1, • 29 weeks gestation• 2 year old son at home, Zachary. • Tiffany cleans houses part time, • Boy friend, Dan, works at McDonalds.• Medicaid
Gestational Case
• More Background• Completed GDM classes, • Testing BG 3-4 times/day• Following meal plan as best she
can. • 2 Food Banks most weeks• No diabetes meds• Grandmother on insulin, had toe
amputated last spring• Afraid of injections
• Objective DataFasting BG: 98mg, 101mg, 114mg, 109mg, 95mg, 118mgBG After meals: 98mg, 118mg, 87mg, BP-118/76
Case Worksheet• Set goals:
• A1c• Glucose goals• Lipid goals
• Priorities• Patient preferences• Cost/Formulary, Use MMIT, finger tip formulary…..
• Initiation and Follow up• SMBG/CGM, Frequency of contact• Adverse events, patient education• Other
1. ADA. Diabetes Care. 2018;41(suppl 1):S1-S159.2. Garber AJ, et al. Endocr Pract. 2018;24:91-120.
Basal Insulin Initiation and Titration: American Diabetes Association Algorithm1
AACE/ACE has also published an algorithm for basal insulin initiation and titration.2
Initial dose: 0.1 to 0.2 U/kg or 10 U/d, depending on the degree of hyperglycemia
BG above target:increase dose by 10% to 15% or
2 to 4 U once or twice weekly to a target of FBG 80-130 mg/dL
Hypoglycemia/BG below target:determine and address cause; reduce
dose by 4 U or 10% to 20%
Be BraveDDo something outside the box
Summary
• Diabetes is a balancing act
• Diabetes is complex and overwhelming- for patients and providers
• Setting glycemic goals must be individualized
• Therapeutic management must be individualized
• Diabetes Self Management Education is important for everyone