Diabetes Flashcards

1
Q

> 65 years old have diabetes

A

~25% of people

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2
Q

> 65 years old have prediabetes

A

~50% of people

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3
Q

Diabetes Increased risk of geriatric syndromes

A
Polypharmacy
• Cognitive impairment
• Depression
• Urinary Incontinence
• Falls and Pain
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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

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5
Q

A1C correlation

A

5= 97 mg/dL
6= 126
7= 154
8=183

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6
Q

Glycemic Goals Healthy Older Adult

A

A1C <7-7.5% (7-7.5%)

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7
Q

Complex/intermediate (multiple chronic illness, ADL impairment or mild-moderate cognitive impairment)

A

A1C <8% (90-150)

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8
Q

Poor Health (end stage chronic illness)

A

avoid hypoglycemia

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9
Q

End of life

A

comfort, avoid hypoglycemia or symptomatic hyperglycemia

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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

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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

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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

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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
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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
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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

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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
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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
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18
Q

Entry A1C <9%

A

start monotherapy Metformin

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19
Q

Entry A1C >9% <10%

A

Dual or Triple Therapy

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20
Q

Entry A1C >10%

A

Combination injectable

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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)

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22
Q

Metformin+Lifestyle+HF (LVEF <45%)

A
Metformin+SGLT2i with
proven benefit (canagliflozin, empagliflozin, dapagliflozin)
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23
Q

Metformin+Lifestyle+CKD

A

Preferred: Metformin+ SGLT2i
(canagliflozin, empagliflozin, apagliflozin)
or
Metformin+GLP-1 RA (dulaglutide, liraglutide, semaglutide (inj only);

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24
Q

Metformin+Lifestyle+ minimize hypoglycemia

A

DPP-4i
GLP-1 RA
SGLT2i
TZD

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25
Q

Metformin+Lifestyle+ minimize weight gain or increase weight loss

A

GLP-1 RA
or
SGLT2i

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26
Q

Metformin+Lifestyle+ low cost

A

TZD pioglitazone
or
SU (Glyburide, Glipizide, Glimepiride)

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27
Q

Diabetic medication combinations to avoid

A
  • GLP-1 RAs with DPP4-I

* SUs with insulin

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28
Q

Oral diabetic med with BBW for HF

A

pioglitazone

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29
Q

Vitamin deficiency caused by Metformin

A

B12

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30
Q

SU 2nd gen adverse affects

A
Hypoglycemia increased in
older adults
• Weight gain
• Glyburide contraindicated in
older adults
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31
Q

Preferred SU in older adults

A

Glipizide is preferred SU

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32
Q

Pioglitazone: favorable CVD profile

A

• 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

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33
Q

Which GLP-1 RA have benefit in ASCVD

A

Neutral: lixisenatide
Benefit: liraglutide, semaglutideᶧ
(Inj), dulaglutide

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34
Q

Which DPP-4i is NOT recommended with CHF

A

Potential Risk: saxagliptin

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35
Q

Which GLP-1 RA is beneficial in CKD

A

Benefit: liraglutide

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36
Q

Renal dosing for GLP-1RA

A

• Exenatide: NR eGFR < 30
• Lixisenatide: caution when eGFR < 30
• Increased risk of SE in patients with renal
impairment

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37
Q

Which DPP-4i does NOT require renal dosing

A

No renal dose adjustment for linagliptin

38
Q

which GLP-1RA increase risk of Thyroid tumors

A

• Box Warning: Risk of thyroid C-cell tumors (liraglutide, albiglutide, dulaglutide,
exenatide ER)

39
Q

What is the mechanism of action for DPP-IV

A
  • Inhibit DPP-4 enzyme
  • Inhibit the degradation of endogenous incretins

Increase insulin secretion
Decrease glucagon secretion
Decrease glucose production
Decreased appetite

40
Q

Renal dosing for DPP-IV

A

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
Q

Hepatic dosing for DPP-IV

A

Saxagliptin (Onglyza®) Moderate to
severe impairment: not recommended

No dose adjustment for others

42
Q

DPP-IV Inhibitors: CV Outcomes

A

No difference in primary outcome; ↑ hospitalizations for HF in saxagliptin arm vs. placebo

43
Q

Mechanism of action for GLP-1 Agonist

A
Activates GLP-1 receptors
•Reduce hepatic gluconeogenesis
•Slows gastric emptying 
•Promotes glucose uptake 
•Increase insulin Secretion
•Decrease glucagon secretion
44
Q
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
A

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
Q

GLP-1 Agonists: CV Benefit

A

SUSTAIN-6 Semaglutide (Inj)
LEADER Liraglutide
REWIND Dulaglutide

46
Q

SGLT-2 Inhibitors ASCVD, CHF, and CKD

A

Benefit:
canagliflozin
depagliflozin
empagliflozin

47
Q

SGLT-2 Risks Canagliflozin

A

• Box Warning: risk of
amputation (canagliflozin)
• Risk of bone fractures
(canagliflozin)

48
Q

SGLT-2 Risks General

A
• DKA risk (rare in T2DM)
• GU infections
• Risk of volume depletion,
hypotension
• Increased LDL cholesterol
• Risk of Fournier’s gangrene
49
Q

SGLT-2i Mechanism of Action

A

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
Q

SGLT-2i Canagliflozin renal dosing

A

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
Q

SGLT-2i renal dosing

A

eGFR <30 mL/min: contraindicated
• Dapagliflozin (Farxiga®),
• Empagliflozin (Jardiance®)
• Ertugliflozin (Steglatro®)

52
Q

How do SGLT-2i cause acidosis

A
↑Glycosuria
↑Volume depletion
↑Glucagon
↑Gluconeogenesis
↑Free-fatty-acid release
↑Ketones
Results in Acidosis
53
Q

EMPA-REG Trial

SGLT-2i Empagliflozin: CVD, HF, and CKD Outcomes

A

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
Q

DECLARE-TIMI 58 Trial

SGLT-2i Dapagliflozin: CVD, HF, and CKD Outcomes

A

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
Q

DAPA-HF Trial

SGLT-2i Dapagliflozin : CVD, HF, and CKD Outcomes

A

Primary Outcome: composite of worsening heart failure or CV death

56
Q

CANVAS CANVAS-R Trial

SGLT-2i Canagliflozin: CVD, HF, and CKD Outcomes

A

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
Q

Credence Trial

SGLT-2i Canagliflozin: CVD, HF, and CKD Outcomes

A

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
Q

Insulin/GLP1 RA

A

Soliqua® (Glargine/Lixisenatide) 100/33 pen

Xultophy® (Degludec/Liraglutide) 100/3.6 pen

59
Q

At what dose are the Pharmacokinetics of U-500 regular insulin become similar to
NPH

A
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
Q

U-500 U/mL Insulin Pearls

A
  • U-500 insulin is five (5) times as concentrated as U-100 insulin
  • Indicated for patients taking greater than 200 units per day
61
Q

Calculate mL of U-500 to give a dose of 100 units

A
• 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
Q

Inhaled Insulin (Afrezza®)

A
  • FDA approved for type 1 and 2 diabetes
  • Ultra rapid-acting
  • Storage constraints
  • Dose conversion constraints
  • Significant upper respiratory ADR
63
Q

When To Use Injectable DM Therapy

A
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
Q

Initiating Insulin Therapy

A
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
Q

Hypoglycemia • Adults 75+

A

• 2x ↑ emergency department (ED)
visits
• 2x ↑ hospitalizations

  • Implicated medications
  • Warfarin (33%)
  • Oral antiplatelet (13%)
  • Insulin (14%)
  • Oral hypoglycemics (11%)
66
Q

Hypoglycemia • Adults 85+

A
  • 2.5x ↑ ED visits

* 5x ↑ hospitalizations

67
Q

Hospitalization in older adults

A
Implicated medications
• Warfarin (33%)
• Oral antiplatelet (13%)
• Insulin (14%)
• Oral hypoglycemics (11%)
68
Q

Unique Considerations of Hypoglycemia in the elderly

A
• ↓ 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
Q

% of diabetes in older adults

A

25% >65 yr have Diabetes

50% >65 yr have prediabetes

70
Q
  • Cognitive decline = increased risk of hypoglycemia
  • Severe hypoglycemia = increased risk of dementia
  • Avoid medications with increased risk of hypoglycemia
A
  • Long-acting sulfonylureas
  • Glimepiride, glyburide
  • Short- or rapid-acting insulins and premixed insulins
71
Q

Criteria for Diagnosis of Diabetes

A
  • Fasting blood glucose (FBG) ≥ 126 mg/dL
  • A1C ≥ 6.5%
  • 2-h blood glucose (BG) ≥ 200 mg/dL during OGTT
72
Q

Who should be tested for diabetes?

A

• > 65 years of age should be tested every 2 years

73
Q

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

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
Q

GLP-1 analogue

A

[tide] Liraglutide (Victoza/Saxenda), Albiglutide (Tanzeum), Dulaglutide (Trulicity), Lixisenatide (Lyxumia), Exenatide (Byetta)

75
Q

DPP-4 Inhibitors

A

[gliptins] Saxagliptin (onglyza), Valdagliptin (Galvus), Alogliptin (Neina/Vipadia) and Sitagliptin (Januvia). All renally dosed except Linagliptin (Tradjenta)

76
Q

LEADER

A

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
Q

EXSCEL

A

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
Q

ELIXA

A

Lixisenatide not demonstrate superiority

79
Q

SUSTAIN-6

A

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
Q

SGLT-2i

A
Canagliflozin (Invokana) : NR
with eGFR < 45
• Dapagliflozin (Forxiga): NR
with eGFR < 60
• Empagliflozin (Jardiance): CI
with eGFR < 30
• Ertugliflozin (Steglatro®): NR GFR<60
81
Q

EMPA-REG

A

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
Q

CANVAS

A

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
Q

CREDENCE

A
Canagliflozin (Invokana)
Composite outcome: ESKD, doubling of serum creatinine,
and renal or CV death
Stopped early due to positive results
Publication pending
84
Q

Best triplicate therapy in older adults

A

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
Q

Combinations to avoid

A
  • GLP-1 RAs with DPP4-I

* SUs with insulin

86
Q

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

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
Q

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

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
Q

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

A. glipizide—least expensive agent
B. exenatide
C. alogliptin
D. canagliflozin

89
Q

Monitoring A1C

A
  • A1C
  • Every 6 months if meeting treatment goals
  • Every 3 months if not meeting treatment goals or if therapy has changed
90
Q

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?

A

B. 3 months—recommended if not meeting treatment goals or if
therapy is changed
C. 6 months
D. 12 months

91
Q

ASCVD

A

atherosclerotic cardiovascular disease

92
Q

antihyperglycemic therapies with positive effects on the kidney

A

SGLT2i or GLP-1 RA