ic12 DM part 1 + IC11 DM Pharmacology Flashcards
What is the diagnosis of Pre-diabetes?
When HBA1C 6.1 - 6.9%, proceed to do FPG or 2hOGTT
then FPG 6.1 - 6.9mmol/L
or
2hOGTT 7.8 - 11.0mmol/L
When should metformin be recommended for people with pre-DM? (2 points)
When glycemic status does not improve despite lifestyle intervention or unable to adopt lifestyle intervention
+
BMI>23, younger than 60, woman with gestational diabetes
What is the contribution of basal VS postprandial hyperglycemia as hba1c increases?
Low Hba1c (< 7.3%) –> Postprandial hyperglycemia contributes more
High Hba1c (> 10.2%) –> Basal hyperglycemia contributes more
How to diagnose no dm, pre-dm, and dm?
No DM
hba1c lower than 6%
if hba1c 6.1-6.9%, fbg < 6 or 2hOGT < 7.8
DM
if Hba1c 6.1-6.9%, fbg > 7 or 2hOGT > 11.1
if Hba1c >7%, confirm diabetes, no tests needed
pre-DM
if hba1c 6.1-6.9%, fbg 6.1 - 6.9 or 2hOGT 7.8 - 11
What are tests for kidney function in DM patients (3 points)
Serum creatinine and eGFR
Urine Albumin / Creatinine ratio (uACR)
Protein-Creatinine Ratio (uPCR)
Goals for non-DM patients (Hba1c, FBG, PPG)
Hba1c < 5.7%
FBG < 5.6
PPG < 7.8
Goals for DM patients
Hba1c < 7%
FBG: 5 - 7
PPG < 10
What are macrovascular and microvascular outcomes of DM?
Macrovascular: Cardiovascular disease eg. stroke, heart attack
Microvascular: Neuropathy (foot), Nephropathy (kidney), retinopathy (eyes)
When should we adopt a more stringent hba1c control for DM patients? (3 points)
More stringent (6 - 6.5%)
Short disease duration
Long life expectancy
No significant cardiovascular diseases
When should we adopt a less strict hba1c control for DM patients? (4 points)
Less stringent (7.5 - 8%)
History of severe hypoglycemia
Limited life expectancy
Advanced complications
Difficulty in achieving target despite intensive Self Monitoring Blood Glucose (SMBG), counselling, effective pharmacotherapy
Primary and Secondary MOA of Metformin
Primary: Inhibit hepatic glucose production
Secondary: Increase tissue sensitivity to insulin
Clinical efficacy of Metformin
What is the additional benefit of Meformin?
Reduce hba1c by 1.5-2%
Does not cause hyperinsulinemia or hypoglycemia
What is the max dose of IR Meformin per day?
Starting dose of IR Metformin
2550mg per day
500-850mg OD, increase frequency to 3 times a day
Starting dose of Metformin XR
Max dose of Metformin XR
500mg OD
Max dose: 2000mg OD or split up to BD
Side effects of Metformin
GI nausea, vomiting, loss of appetite, metallic taste
Long term: Vitamin B12 deficiency -> cause numbness
Rare: Lactic acidosis
Which special population can take metformin?
Which patient should not take Metformin XR
Pregnant can take
Children cannot take
Contraindicated populations for Metformin (2 points)
1) Severe renal impairment: GFR < 30ml/min
2) Patient at risk for hypoxia, lactic acidosis eg. heart failure, sepsis
Drug interactions with Metformin (3 points)
1) Alcohol
Increase risk of lactic acidosis
2) Iodinated contrast material
Cause unstable renal function
Withhold metformin for at least 48hrs
Inhibitors or Inducers of Organic
3) Cationic transporters (OCT)
Eg. Cimetidine, Dolutegravir, Ranolazine
MOA of TZD
Example of TZD
PPAR agonist, increase insulin sensitivity
increase uptake of glucose into skeletal muscle and adipose tissue
Pioglitazone
Starting dose and Max dose of Pioglitazone
Start with 15-30mg OD
Max: 45mg OD
When to discontinue TZD?
When ALT > 3x ULN
Adverse effects of TZD (3 points)
Fluid retention, Weight gain from fluid retention
Fracture
Risk of bladder cancer
Contraindicated populations for TZD (3 points)
1) Active liver disease
2) Symptomatic or history of heart failure
3) Active or history of bladder cancer
Efficacy of TZD in Hba1c
Other benefit?
0.5% - 1.4%
Beneficial for patients with Fatty liver disease (even though its hepatotoxic)
Similarity and Difference between Metformin and TZD
Similarity:
Similar MOA, both increase tissue sensitivity to insulin
Difference
Metformin is renally cleared, cannot use when CrCl <30ml/min
TZD is hepatotoxic
What are some examples of Sulfonyureas?
MOA of SU? (Primary, Secondary)
Glipizide, Gliclazide MR
Primary: Stimulate secretion by blocking K+ channels of beta cells
Secondary: Decrease hepatic glucose output and Increase insulin sensitivity
What happens to SU in beta cell, and how does it cause insulin release?
SU inhibit receptor protein SUR1, inhibit K+ from releasing from beta cells
Accumulation of K+ cause depolarisation, which causes voltage sensitive Ca2+ to open and allow Ca2+ to enter
Ca2+ causes release of insulin
How are most SU eliminated?
Which SU should be used for renal impairment?
Renally
Glipizide
Counselling point of SU
Take 15-30 mins before meal so to allow release of insulin before eating
Adverse effects of SU (2 points)
1) Hypoglycemia, esp in elderly that eat little
2) Weight gain (2-5kg)
Drug drug interactions with Glipizide (3 points)
1) Beta blockers: can mask symptoms of hypoglycemia
2) Alcohol: disulfiram like reaction, use 2nd or 3rd gen instead
3) CYP2C9 inhibitors
Clinical efficacy of SU
Lower hba1c by 1.5%
MOA of DPP4i
Examples of DPP4i and their doses (3 points)
Inhibit the breakdown of incretins eg. GLP1, which triggers insulin production, decrease glucagon secretion, slow gastric emptying and feel full
Sitagliptin 100mg OD
Vildagliptin
50mg OD with SU
50mg BD with Metformin or TZD
(how to rmb: higher dose with agents that dont increase insulin)
Linagliptin 5mg OD
Adverse effects of DPP4i
Severe joint pain
Acute pancreatitis
Clinical efficacy of DPP4i if used as monotherapy
0.5-0.8% reduction in hba1c
MOA of SGLT2i
Inhibit transporters in proximal tubule
→ blocking reabsorption of glucose
→ increase renal glucose excretion
Examples of SGLT2i and doses
Dapagliflozin 5, 10mg OD
Empagliflozin 10, 25mg OD
Adverse effects of SGLT2i (4 points)
Increased urination
Urinary tract infection
Diabetic Ketoacidosis
Hypotension
What is diabetic ketoacidosis?
Who does it frequently occur in?
When high sugar and low insulin, body cannot use sugar to produce insulin
Hence will convert fats to energy instead, and ketones are produced also
usually occurs in type 1 DM
Renal considerations for SGLT2i
If want glycemic control, must be more strict
(dont initiate, discontinue) eGFR <45
If want big 3 cardiorenal benefit , can be more lenient
(dont initiate) eGFR < 25 for Dapa, eGFR < 20 for Empa
(discontinue) patient start dialysis
When SGLT2i is used for glycemic control on patients with no cardio conditions, what is the cut off for initiation? (egfr < __)
When eGFR < 45
When patient has comorbidities eg. HF, MI, CKD, what is the cut off for SGLT2i initiation?
Do not initiate if EGFR < 25 for dapa and < 20 for empa
Stop when patient starts dialysis
Hba1c reduction of SGLT2i
0.8 - 1%
Out of the SGLT2i, use which one for ASCVD, Heart failure, CKD?
ASCVD: Empa
HF, CKD: Dapa
what are the big 3 outcomes for SGLT2i?
ASCVD, HF, CKD
What class of drugs is Arcabose?
MOA of Arcabose
a-glucosidase inhibitors
Delay glucose absorption by blocking breakdown and absorption of carbs in GI
Only works for Post Prandial glucose, not Fasting glucose
Starting dose of Acarbose
25mg 2-3x a day with each meal
Max dose: 150mg a day (60kg or less), 300mg a day (>60kg)
Adverse effects of Acarbose
GI flatulence, abdominal pain, diarrhoea
What is the class that acts as Incretins?
Example and dose?
GLP1 receptor agonist
Liraglutide
0.6mg, 1.2mg (1 week), 1.8mg
Semaglutide
(SC injection) 0.25mg, 0.5mg (1 month), 1mg
(PO) 3mg, 7mg (1 month), 14mg
Dulaglutide
0.75mg, 1.5mg (1 month), 3mg, 4,5mg
Which GLP 1 agonist needs to be taken on empty stomach?
Semaglutide oral, 30 mins before eating
the other SC injections can be taken anytime
Adverse effects of GLP-1
Headache
Nausea, vomiting
acute pancreatitis
Absolute contraindication with GLP-1 agonist
Thyroid cancer
MOA of GLP-1
Bind to GLP-1 receptor found in beta cells, Increase insulin secretion and Decrease glucagon release, decrease gastric emptying, make you feel full
Which drug works on fasting BG the most? Why?
Metformin, cos it targets the hepatic glucose output
Drugs good for weight loss
Metformin (ic11)
GLP-1 agonist
SGLT2i (slight weight loss)
Drugs with risk of hypoglycemia
Insulin
SU
Drugs that can cause weight gain
TZD (from fluid retention)
SU (2-5kg)
Insulin
Drugs that can increase insulin sensitivity
Metformin (secondary)
TZD
SU (secondary)
Drugs contraindicated with Alcohol
Metformin (increase risk of lactic acidosis)
SU (disulfiram like reaction, worse with Tolbutamide)
Drugs taken with relation to food
15 mins before food:
Sulfonylurea
With food:
Acarbose
On empty stomach:
PO Semaglutide
Drugs that have big 3 benefits
SGLT2i
GLP-1 Agonists
