Type 2 Diabetes Management Flashcards
Core management of T2DM consists of…
Self-management
Lifestyle modifications
Pharmacotherapy
When choosing therapy for T2DM, assess the following…
BG? other factors? lifestyle?
Glycemic control, CV + renal status, dietary patterns and weight changes.
Individualized A1C targets can be chosen using…
The Canadian Diabetes A1C calculator
There are three options when beginning therapy for T2DM:
Lifestyle changes; no pharmacotherapy
Starting metformin (+ second agent if A1C is 1.5% above target)
Starting insulin + metformin for symptomatic hyperglycemia
If A1C is not at target at 3 months, next steps include…
Starting metformin if not on pharmacotherapy
Adjust or advance therapy
The MOA of metformin involves the following…
3 components
Decreasing hepatic glucose production
Enhancing sensitivity to insulin + increase glucose utilization
Some anti-inflammatory, effect on gut microbiome
Dosing of metformin should be initiated slowly, at…
250-500mg once daily
Metformin can be titrated by ____ weekly, if there are no GI side effects.
500mg weekly
Desired dosing for metformin is…
850-1000mg BID
Max dose: 850mg TID
The XR formulation of metformin can be dosed…
Once or twice daily
Metformin’s efficacy on A1C is…
What about TG, LDL, HDL? Clinical outcomes?
1-1.5% (up to 2% in certain patients)
Shown to lower TG, LDL, and slightly increase HDL
Lowered MI + mortality in T2 patients with obesity
Metformin has a negative interaction with alcohol as it can…
Potentiate metformin’s effect on lactate metabolism (lactic acidosis)
Enhance hypoglycemic effect
Common adverse effects with metformin include:
GI - diarrhea, nausea, abdominal discomfort
If GI side effects are bothersome from metformin, we can try…
Taking it with food, or try the XR formulation (Glumetza)
Less common adverse effects that may result from metformin include:
Metallic taste (lasting for a few weeks)
Vitamin B12 deficiency with long-term use (>5 years)
Signs of B12 deficiency involve…
Anemia, peripheral neuropathy
Risk of hypoglycemia with metformin is…
Very low when used as monotherapy, perhaps with concomitant factors (alcohol, not eating, usage with sulfonylurea)
Metformin effect on weight is…
Weight neutral to modest weight loss
Metformin max effect is reached in…
~2 weeks
Lactic acidosis is a condition where…
Arterial pH is lowered, and accumulation of serum lactate is present
S/Sx’s of lactic acidosis include…
Weakness, malaise, myalgias, and heavy laboured breathing
Metformin is potentially correlated with lactic acidosis, due to…
Inhibiting the conversion of lactate into glucose in the liver
Those who are primarily at risk of lactic acidosis with metformin are those who have…
Kidney
Reduced eGFR - lactate is eliminated unchanged by the kidneys, so there will be reduced elimination
THEREFORE dose is reduced with impaired renal function
May be withheld or d/c depending on certain precautions
Renal impairment doses start when Clcr is below…
<60 mL/min
eGFR between 45-59 warrants metformin dosing of…
1500 mg/day in divided doses
eGFR between 30-44 warrants metformin dosing of…
1000mg/day in divided doses
Check eGFR every 3 months
Metformin is CI when eGFR is ____. However, new studies have shown that with eGFR of ____, metformin could be continued at 500mg od but not started.
CI when eGFR is <30 mL/min. eGFR of 15-30 mL/min, do not start but can continue at metformin 500mg od
Risk factors for lactic acidosis involve the kidney or liver, such as…
Severe liver disease or alcohol abuse, acute illness, or severe dehydration
Also consider history of lactic acidosis
The MOA of sulfonylureas involve…
AKA insulin secratagogues
Enhancing secretion of insulin via binding to SU receptors on the beta cells of the pancreas
Stimulate both basal + meal-stimulated insulin release
2nd generation sulfonylureas include these three drugs…
Glyburide
Gliclazide
Glimepiride
These two sulfonylureas ARE on the formulary:
Glyburide and gliclazide MR
Usual dosing for glyburide is…
5mg BID, up to 10mg BID
Usual dosing for gliclazide MR is…
30-120mg OD
Are sulfonylureas CI in renal failure?
Discussing formulary ones
Glyburide is CI in eGFR <60 mL/min.
Gliclazide is cautioned in 30-60 mL/min, CI in eGFR <30 mL/min
Sulfonylurea effect on A1C is…
1-1.5%, (up to 2% in drug naive and elevated A1C)
Sulfonylureas work quickly, and doses can be titrated…
After 2 weeks based on fasting BG, then titrate every 1-2 weeks
The max effective dose is reached at about ____ of the maximum dosage
60-75%
Long-term durability/efficacy of sulfonylureas is poor because…
Overtime, the pancreas will produce less insulin
Therefore, better response may be achieved if initiated early
How do sulfonylureas compare with CV outcomes?
Microvascular benefit, but neutral for macrovascular benefit
Hypoglycemia risk with sulfonylureas is…
High incidence, 2-30%
Do sulfonylureas affect weight?
Yes, weight gain ~2kg
Which sulfonylureas are more likely to cause hypoglycemia?
Glyburide > glimepiride > gliclazide
If sulfonylureas are used in the elderly, what needs to be done with the dose to help prevent hypoglycemia?
Initiate at half normal dose, and titrate up
Less freqent adverse effects that occur with sulfonylureas include…
Nausea
Rash, photosensitivity
Cross-sensitivity with those with a sulfa allergy is very rare
Sulfonylureas are contraindicated in…
Pregnancy/breast-feeding
Severe hepatic/renal impairment
Sulfonylureas should be held in acute illness due to…
Higher risk of hypoglycemia
Drug interactions with sulfonylureas that may increase risk of hypoglycemia include…
Other sulfonamides, alcohol Salicylates, warfarin, NSAID’s, beta-blockers, MAOI’s
Bold = important ones
Some drugs used with sulfonylureas may lead to lessened effects, and increased BG, such as…
Phenytoin
Rifampin
Colesevelam
Repaglinide is in a group of drugs known as …
Short-acting, or non-SU insulin secretagogues
Meglitinides
Repaglinide’s MOA is to…
Bind to site adjacent to SU receptor, resulting in stimulation of secretion of insulin from the pancreas
Repaglinide differs from other sulfonylureas because…
PK? When is it supposed to be taken?
It has a faster onset and shorter duration of action; works primarily to decrease PPG
Peak levels within 1 hour, and half-life is 1 hour
Repaglinide’s effect on A1C is…
Differs in how it affects BG !
1 to 1.5%; primarily decreases PPG - intended to be taken before meals to improve bolus insulin release
Repaglinide dosing should be initiated based on…
Does it differ based on patient condition?
A1C: If below 8%, start at 0.5mg doses and titrate up. If above 8%, start at 1-2mg doses and titrate up.
LOW doses
Repaglinide should be titrated every…
1-2 weeks until target BG is achieved
Max dose of repaglinide should be:
4mg, before each meal: max dose of 16mg/day
Due to its short duration of action, repaglinide needs to be administered…
Right before a meal, within 30 minutes
Repaglinide is unique as it provides some flexibility, where a patient can…
Skip a meal, skip a dose; add a meal, add a dose
Repaglinides relationship to hypoglycemia is…
Higher risk, especially when combined with other agents
Lesser extent compared to SU’s, and flexibility with meal dosing
Do repaglinides affect weight?
Yes, weight gain ~0.3 to 1kg
Similar to SU’s but to a lesser extent
Another common adverse effect with repaglinide are…
Headaches
Repaglinide needs to be used with caution in…
Impairment
CrCl < 30mL/min
Caution in moderate hepatic impairment and CI in severe liver disease
Clearance significantly reduced in hepatic impairment: CYP450
Repaglinide concentrations increase when used with:
Which CYP enzymes??
3A4 and 2C8 inhibitors
…Repaglinide conc. decreased with 3A4 inducers
