Diabetes Flashcards
1
Q
> 65 years old have diabetes
A
~25% of people
2
Q
> 65 years old have prediabetes
A
~50% of people
3
Q
Diabetes Increased risk of geriatric syndromes
A
Polypharmacy • Cognitive impairment • Depression • Urinary Incontinence • Falls and Pain
4
Q
Diabetes Diagnostic Criteria 2021 ADA
A
A1C>6.5% or 8hr FPG >126mg/dL, 2hr plasma glucose >200mg/dL, Random plasma glucose >200mg/dL
5
Q
A1C correlation
A
5= 97 mg/dL
6= 126
7= 154
8=183
6
Q
Glycemic Goals Healthy Older Adult
A
A1C <7-7.5% (7-7.5%)
7
Q
Complex/intermediate (multiple chronic illness, ADL impairment or mild-moderate cognitive impairment)
A
A1C <8% (90-150)
8
Q
Poor Health (end stage chronic illness)
A
avoid hypoglycemia
9
Q
End of life
A
comfort, avoid hypoglycemia or symptomatic hyperglycemia
10
Q
Time to benefit of low A1C
A
benefit of A1C 7 or less declines after 9 years, if life expectancy is short, tight control has no benefit
11
Q
Blood Glucose Monitoring • Basal insulin or oral agents
A
Insufficient evidence
• Varies by patient, but consider in: suspected or frequent hypoglycemia, prior
to exercise or critical tasks
12
Q
Blood Glucose Monitoring • Intensive insulin
A
• Fasting, prior to meals/snacks, bedtime, occasionally post-prandial,
hypoglycemia suspected; also consider prior to exercise or other critical tasks
• At least 3 times daily, may require 6-10 times per day
13
Q
Continuous Glucose Monitoring (CGM) Real-Time CGM (rtCGM)
A
• Most data from RCTs • Continuous reporting, alarms for excursions • Calibrate BID with fingersticks • Newest Dexcom G6 does not require • Reduced time in hypoglycemia rtCGM > isCMG
14
Q
Continuous Glucose Monitoring (CGM)
A
• Reports only on demand (swiped by a reader or smart phone) • No fingerstick calibration needed • Does not have alarms for excursions • FreeStyle Libre 2 has real time alarms for high or low glucose levels • Must be scanned at least every 8 hours to avoid gaps in glucose trends
15
Q
Continuous Glucose Monitoring (CGM) benefits and coverage
A
Best A1C ↓ if high baseline
• NOT shown to reduce hypoglycemia in T2DM
• May ↓ nocturnal hypoglycemia (rtCGM)
• MAY ↑ satisfaction, time in range
• Medicare covers Dexcom G6 and FreeStyle Libre 2 for T1D/T2D
• Prescribed insulin four times daily
• Checking blood glucose four times daily
16
Q
Lifestyle and Psychosocial Care for diabetes
A
Aerobic activity • ~30 min/day most days of the week • No more than 2 days between exercise sessions • Resistance training • 2-3 sessions per week • Flexibility and balance exercises particularly important for > 65 years Optimal nutrition and protein intake • Diabetes is an independent risk factor for frailty • Referral to psychology or counselor if concerns with emotional health
17
Q
Diabetes Medication Therapy in Older Adults
A
- Medication classes with low risk of hypoglycemia are preferred
- Avoid overtreatment of diabetes
- Simplify complex regimens
18
Q
Entry A1C <9%
A
start monotherapy Metformin
19
Q
Entry A1C >9% <10%
A
Dual or Triple Therapy
20
Q
Entry A1C >10%
A
Combination injectable
21
Q
Metformin+Lifestyle+atherosclerotic cardiovascular disease (ASCVD)
A
Metformin+ Agent with
proven CVD benefit
1. GLP-1 RA (dulaglutide, liraglutide, semaglutide (inj only)) or
2. SGLT2i (canagliflozin, empagliflozin, dapagliflozin)
22
Q
Metformin+Lifestyle+HF (LVEF <45%)
A
Metformin+SGLT2i with proven benefit (canagliflozin, empagliflozin, dapagliflozin)
23
Q
Metformin+Lifestyle+CKD
A
Preferred: Metformin+ SGLT2i
(canagliflozin, empagliflozin, apagliflozin)
or
Metformin+GLP-1 RA (dulaglutide, liraglutide, semaglutide (inj only);
24
Q
Metformin+Lifestyle+ minimize hypoglycemia
A
DPP-4i
GLP-1 RA
SGLT2i
TZD
25
Metformin+Lifestyle+ minimize weight gain or increase weight loss
GLP-1 RA
or
SGLT2i
26
Metformin+Lifestyle+ low cost
TZD pioglitazone
or
SU (Glyburide, Glipizide, Glimepiride)
27
Diabetic medication combinations to avoid
* GLP-1 RAs with DPP4-I
| * SUs with insulin
28
Oral diabetic med with BBW for HF
pioglitazone
29
Vitamin deficiency caused by Metformin
B12
30
SU 2nd gen adverse affects
```
Hypoglycemia increased in
older adults
• Weight gain
• Glyburide contraindicated in
older adults
```
31
Preferred SU in older adults
Glipizide is preferred SU
32
Pioglitazone: favorable CVD profile
• Insulin sensitization
• ↓TG, ↑HDL, ↓atherogenic LDL
• ↓ Blood pressure
• ↓ Inflammatory markers and pro- coagulant factors
PROACTIVE: Reduced risk of MACE (major adverse cardiac events) in
T2DM with existing CVD
• IRIS: Reduced CV events in insulin- resistant non-diabetics with recent
cerebrovascular event
• TOSCA-IT: Did NOT reduce CV
outcomes in SU-treated, T2DM
without ASCVD
• Decreases risk of restenosis after stent
placement
33
Which GLP-1 RA have benefit in ASCVD
Neutral: lixisenatide
Benefit: liraglutide, semaglutideᶧ
(Inj), dulaglutide
34
Which DPP-4i is NOT recommended with CHF
Potential Risk: saxagliptin
35
Which GLP-1 RA is beneficial in CKD
Benefit: liraglutide
36
Renal dosing for GLP-1RA
• Exenatide: NR eGFR < 30
• Lixisenatide: caution when eGFR < 30
• Increased risk of SE in patients with renal
impairment
37
Which DPP-4i does NOT require renal dosing
No renal dose adjustment for linagliptin
38
which GLP-1RA increase risk of Thyroid tumors
• Box Warning: Risk of thyroid C-cell tumors (liraglutide, albiglutide, dulaglutide,
exenatide ER)
39
What is the mechanism of action for DPP-IV
* Inhibit DPP-4 enzyme
* Inhibit the degradation of endogenous incretins
Increase insulin secretion
Decrease glucagon secretion
Decrease glucose production
Decreased appetite
40
Renal dosing for DPP-IV
Sitagliptin (Januvia®): <30 mL/min 25 mg daily
Saxagliptin (Onglyza®) ≤ 50 mL/min
2.5 mg daily
Linagliptin (Tradjenta®, Trajenta®) No dose
adjustment
Alogliptin (Nesina®) 15-29 mL/min 6.25 mg daily
41
Hepatic dosing for DPP-IV
Saxagliptin (Onglyza®) Moderate to
severe impairment: not recommended
No dose adjustment for others
42
DPP-IV Inhibitors: CV Outcomes
No difference in primary outcome; ↑ hospitalizations for HF in saxagliptin arm vs. placebo
43
Mechanism of action for GLP-1 Agonist
```
Activates GLP-1 receptors
•Reduce hepatic gluconeogenesis
•Slows gastric emptying
•Promotes glucose uptake
•Increase insulin Secretion
•Decrease glucagon secretion
```
44
```
GLP-1 Agonist dosing
Note:
Semaglutide (Rybelsus) is the only PO
Lisixenatide has weight loss in 12 Weeks
Semaglutide inj (Ozempic) has the most weight loss
```
Agent • Sig • Weight Loss (kg)
Exenatide (Byetta®) 5 mcg or 10 mcg SQ BID 2.9KG at 30 weeks
Exenatide ER (Bydureon®) 2mg SQ QW 2.3KG at 24 weeks
Liraglutide (Victoza®) 0.6, 1.2, or 1.8mg SQ QD 2.5KG at 30 weeks
Dulaglutide (Trulicity®) 0.75 or 1.5mg SQ QW 2.5kg at 26 weeks
Lisixenatide (Adlyxin®) 10 or 20 mcg SQ QD 1.94Kg at 12 WEEKS
Semaglutide (Ozempic®) Weekly (Inj) 0.25, 0.5, or 1 mcg SQ QW 4.7kg at 30 weeks
Semaglutide (Rybelsus®) 3, 7, or 14 mg PO QD 3.7KG at 26 weeks
45
GLP-1 Agonists: CV Benefit
SUSTAIN-6 Semaglutide (Inj)
LEADER Liraglutide
REWIND Dulaglutide
46
SGLT-2 Inhibitors ASCVD, CHF, and CKD
Benefit:
canagliflozin
depagliflozin
empagliflozin
47
SGLT-2 Risks Canagliflozin
• Box Warning: risk of
amputation (canagliflozin)
• Risk of bone fractures
(canagliflozin)
48
SGLT-2 Risks General
```
• DKA risk (rare in T2DM)
• GU infections
• Risk of volume depletion,
hypotension
• Increased LDL cholesterol
• Risk of Fournier’s gangrene
```
49
SGLT-2i Mechanism of Action
inhibits sodium-glucose cotransporter 2 (SGLT2) in the proximal tubule, thereby reducing reabsorption of filtered glucose, lowering the renal threshold for glucose, and increasing urinary glucose excretion
50
SGLT-2i Canagliflozin renal dosing
Canagliflozin (Invokana®) eGFR <30 mL/min with: Urinary albumin excretion >300 mg/day: 100 mg once daily
Urinary albumin excretion ≤300 mg/day: contraindicated
51
SGLT-2i renal dosing
eGFR <30 mL/min: contraindicated
• Dapagliflozin (Farxiga®),
• Empagliflozin (Jardiance®)
• Ertugliflozin (Steglatro®)
52
How do SGLT-2i cause acidosis
```
↑Glycosuria
↑Volume depletion
↑Glucagon
↑Gluconeogenesis
↑Free-fatty-acid release
↑Ketones
Results in Acidosis
```
53
EMPA-REG Trial
| SGLT-2i Empagliflozin: CVD, HF, and CKD Outcomes
Decreased rate of hospitalization due to HF [HR 0.65 (CI 0.50-0.85)]
Decreased incident or worsening nephropathy [HR 0.61 (CI 0.53-0.70), p <0.001]
Superiority met for primary CVD outcome (p=0.04)
54
DECLARE-TIMI 58 Trial
| SGLT-2i Dapagliflozin: CVD, HF, and CKD Outcomes
Decreased rate of hospitalization due to HF [HR 0.73 (CI 0.61-0.88)]
Decreased rate of renal event[HR 0.76 (CI 0.67-0.87)] Superiority not met
55
DAPA-HF Trial
| SGLT-2i Dapagliflozin : CVD, HF, and CKD Outcomes
Primary Outcome: composite of worsening heart failure or CV death
56
CANVAS CANVAS-R Trial
| SGLT-2i Canagliflozin: CVD, HF, and CKD Outcomes
Decreased rate of hospitalization due to HF [HR 0.65 (CI 0.52-0.87)]
Decreased progression of albuminuria [HR 0.73 (CI 0.67-0.79)]
Decreased reduction in eGFR, renal-replacement therapy, or renal death
Superiority met for primary CVD outcome (p=0.02)
57
Credence Trial
| SGLT-2i Canagliflozin: CVD, HF, and CKD Outcomes
Primary Outcome: Composite ESRD, doubling of SCr, death from renal/CVD
Decreased rates of primary outcome[HR 0.70 (CI 0.59-0.82), p<0.00001]
Decreased MACE [HR 0.74 (CI 0.63 – 0.86), p=NR]
Decreased rate of hospitalization due to HF [HR 0.61 (CI 0.47 – 0.80), p<0.001]
58
Insulin/GLP1 RA
Soliqua® (Glargine/Lixisenatide) 100/33 pen
Xultophy® (Degludec/Liraglutide) 100/3.6 pen
59
At what dose are the Pharmacokinetics of U-500 regular insulin become similar to
NPH
```
at doses greater than 0.12mL
After 0.2 units/kg
Onset: 30 minutes
Peak: 1.75-4 hours
Duration: 6 to >10 hours
High concentration promotes aggregation
```
60
U-500 U/mL Insulin Pearls
* U-500 insulin is five (5) times as concentrated as U-100 insulin
* Indicated for patients taking greater than 200 units per day
61
Calculate mL of U-500 to give a dose of 100 units
```
• To calculate units to mL: divide by 500
• Example: Order = 100 units of U-500
insulin
• 100/500 = 0.2mL of U-500 insulin
• 0.2mL = 20 units on a U-100 insulin
syringe
• 20 units (on a U-100 syringe) x 5 = 100
units delivered
```
62
Inhaled Insulin (Afrezza®)
* FDA approved for type 1 and 2 diabetes
* Ultra rapid-acting
* Storage constraints
* Dose conversion constraints
* Significant upper respiratory ADR
63
When To Use Injectable DM Therapy
```
Not at goal (despite dual/triple therapy)
• GLP1RA
• Basal Insulin
A1C >10% or >2% above goal
• Basal + GLP1RA
• Basal + Prandial
Not at goal despite basal titration
• Prandial
```
64
Initiating Insulin Therapy
```
Start Basal
• 10 units
• 0.1-0.3 units/kg
Intensify Basal
• 2-3 units at a time
• 10-20% of TDD
Start Prandial
• GLP1-RA
• Insulin: 4 units or 10% of basal insulin dose
• Usually with largest meal or meal with greatest post-prandial excursion
```
65
Hypoglycemia • Adults 75+
• 2x ↑ emergency department (ED)
visits
• 2x ↑ hospitalizations
* Implicated medications
* Warfarin (33%)
* Oral antiplatelet (13%)
* Insulin (14%)
* Oral hypoglycemics (11%)
66
Hypoglycemia • Adults 85+
* 2.5x ↑ ED visits
| * 5x ↑ hospitalizations
67
Hospitalization in older adults
```
Implicated medications
• Warfarin (33%)
• Oral antiplatelet (13%)
• Insulin (14%)
• Oral hypoglycemics (11%)
```
68
Unique Considerations of Hypoglycemia in the elderly
```
• ↓ Symptom recognition
• Less intense symptoms
• Start at lower levels
• Fast psychomotor deterioration
• Only 8% older patients correctly
reported hypoglycemia vs 50%
middle-aged
• Medication management
• Too much short acting with meals
• Wrong dose/product
• Wrong time of day
• Self over-correcting
• Over-basalization
```
69
% of diabetes in older adults
25% >65 yr have Diabetes
| 50% >65 yr have prediabetes
70
* Cognitive decline = increased risk of hypoglycemia
* Severe hypoglycemia = increased risk of dementia
* Avoid medications with increased risk of hypoglycemia
* Long-acting sulfonylureas
* Glimepiride, glyburide
* Short- or rapid-acting insulins and premixed insulins
71
Criteria for Diagnosis of Diabetes
* Fasting blood glucose (FBG) ≥ 126 mg/dL
* A1C ≥ 6.5%
* 2-h blood glucose (BG) ≥ 200 mg/dL during OGTT
72
Who should be tested for diabetes?
• > 65 years of age should be tested every 2 years
73
KC is a 73 yo Caucasian male recently diagnosed with T2DM. His PMH includes
T2DM, HTN, peripheral neuropathy, OA, and dyslipidemia. He also reports mild
memory loss and difficulty managing his medications. His medications include
metformin, HCTZ, Lisinopril, Tylenol, and pravastatin. Which of the following is the
most appropriate A1C goal for KC?
A. < 7% -- not appropriate for older adults
B. < 7.5 % -- no diabetes comorbidities, 1-2 non-diabetic chronic illnesses, no ADL
impairments, ≤ 1 IADL, no cognitive impairment
C. < 8% – ≥ 3 non-diabetes chronic illnesses and/or any one of the following:
mild cognitive impairment/early dementia, ≥ 2IADL impairments
D. < 8.5% -- one of the following: end stage medical condition(s), moderate severe
dementia, ≥ 2 ADL impairments, residence in LTCF/SNF
74
GLP-1 analogue
[tide] Liraglutide (Victoza/Saxenda), Albiglutide (Tanzeum), Dulaglutide (Trulicity), Lixisenatide (Lyxumia), Exenatide (Byetta)
75
DPP-4 Inhibitors
[gliptins] Saxagliptin (onglyza), Valdagliptin (Galvus), Alogliptin (Neina/Vipadia) and Sitagliptin (Januvia). All renally dosed except Linagliptin (Tradjenta)
76
LEADER
Liraglutide
Noninferiority design.
Pts: T2DM with high CV risk (n=9340)
Outcomes: Composite CV death, nonfatal MI & stroke
Results: Noninferior to placebo [HR 0.87 (CI 0.78-0.97),
p<0.001). Demonstrated superiority (p=0.01)
77
EXSCEL
Exenatide
Noninferiority design.
Pts: T2DM with high CV risk or CV disease (n=14,752)
Outcomes: Composite CV death, nonfatal MI & stroke
Results: Noninferior to placebo [HR 0.91 (CI 0.83-1.00)]. No
demonstrate superiority (p=0.02)
78
ELIXA
Lixisenatide not demonstrate superiority
79
SUSTAIN-6
Noninferiority design.
Pts: T2DM with high CV risk or CV disease (n=3,297)
Outcomes: Composite CV death, nonfatal MI & stroke
Results: Noninferior to placebo [HR 0.74 (CI 0.58-0.95),
p<0.001)]. Demonstrate superiority (p=0.02)
80
SGLT-2i
```
Canagliflozin (Invokana) : NR
with eGFR < 45
• Dapagliflozin (Forxiga): NR
with eGFR < 60
• Empagliflozin (Jardiance): CI
with eGFR < 30
• Ertugliflozin (Steglatro®): NR GFR<60
```
81
EMPA-REG
Empagliflozin (Jardiance)
Noninferiority design.
Pts: T2DM with high CV risk (n=7020)
Primary Outcome: Composite CV death, nonfatal MI &
stroke
Results: Noninferior to placebo [HR 0.86 (CI 0.74 – 0.99),
p<0.001]. Demonstrated superiority (p=0.04).
82
CANVAS
Canagliflozin (Invokana)
Noninferiority design.
Pts: T2DM with high CV risk (n=10142)
Outcomes: Composite CV death, nonfatal MI & stroke
Results: Noninferior to placebo [HR 0.86 (CI 0.75-0.97),
p<0.001). Demonstrated superiority (p=0.02)
83
CREDENCE
```
Canagliflozin (Invokana)
Composite outcome: ESKD, doubling of serum creatinine,
and renal or CV death
Stopped early due to positive results
Publication pending
```
84
Best triplicate therapy in older adults
GLP-1, DPP-4 OK in older, if renal function allows Metfromin+GLP-1 + Basal Insulin 10 units/day and titrating up, Insulin is more cost effective
85
Combinations to avoid
* GLP-1 RAs with DPP4-I
| * SUs with insulin
86
OW is a 73 year old female diagnosed with T2DM 6 months ago. Her
PMH includes T2DM, HTN, dyslipidemia, PVD, h/o TIAs, and HF. Her
current medications include metformin, losartan, metoprolol, HCTZ,
furosemide, atorvastatin, and aspirin. Based on OW’s PMH, which of
the following is the best antihyperglycemic agent in addition to
metformin?
A. Pioglitazone– possible ASCVD benefit, increased risk HF
B. Saxagliptin– neutral ASCVD, neutral HF
C. Glipizide—Neutral ASCVD, neutral HF
D. semaglutide– ASCVD benefit, neutral for HF
87
MS is an 82 year old male living independently. His PMH includes
T2DM, HTN, and OA? His current medications include metformin,
lisinopril, and acetaminophen. His most recent A1C was 8.2%. Based
on MS’ PMH and medications, what is the most appropriate treatment
goal?
A. < 7% -- not appropriate for older adults
B. < 7.5 % -- no diabetes comorbidities, 1-2 non-diabetic chronic illnesses, no
ADL impairments, ≤ 1 IADL, no cognitive impairment
C. < 8% – ≥ 3 non-diabetes chronic illnesses and/or any one of the following:
mild cognitive impairment/early dementia, ≥ 2IADL impairments
D. < 8.5% -- one of the following: end stage medical condition(s), moderatesevere
dementia, ≥ 2 ADL impairments, residence in LTCF/SNF
88
MS is an 82 year old male living independently. His PMH includes T2DM, HTN,
and OA. His current medications include metformin, Lisinopril, and Tylenol.
His most recent A1C was 8.2%. MS has resisted additional medications for
diabetes due to cost. He refuses to take any medication requiring injections.
He has Medicare and does not qualify for patient assistance. Based on MS’
PMH and concern with cost, which of the following is the best
antihyperglycemic agent in addition to metformin?
A. glipizide—least expensive agent
B. exenatide
C. alogliptin
D. canagliflozin
89
Monitoring A1C
* A1C
* Every 6 months if meeting treatment goals
* Every 3 months if not meeting treatment goals or if therapy has changed
90
MS is an 82 year old male living independently. His PMH includes
T2DM, HTN, and OA. His current medications include metformin,
lisinopril, and Tylenol. His most recent A1C was 8.2%. Based on MS’
A1C and medications, when is the most appropriate time for an A1C
recheck?
B. 3 months—recommended if not meeting treatment goals or if
therapy is changed
C. 6 months
D. 12 months
91
ASCVD
atherosclerotic cardiovascular disease
92
antihyperglycemic therapies with positive effects on the kidney
SGLT2i or GLP-1 RA
