specific characteristics of different anti hyperglycemic agents Flashcards
Which medications enhances the clearance of repaglinide and which ones reduce its clearance?
Repaglinide clearance enhanced by CYP 3A4 inducers (CBZ and rifampin
repaglinide clearance is reduced by CYP3A4 inhibitors (Azole antifungals, macrolide and protease inhibitors)
CYP2C8 inhibitors (Atazanavir, ritonavir, Gemfibrozil)
What is the frequency of semaglutide, liraglutide, eventide, dulaglutide and lixisenatide administration?
Dulaglutide and semaglutide once weekly
Liraglutide and lixisenatide once daily
Exenatide solution SC twice daily B4 meals
Exe native suspension once weekly
Who are the candidates for basal insulin only and what is the standard starting dose?
In people with T2DM
To start with 5-10 Units at bedtime
What are the sign/symptoms of mild, moderate, severe hypoglycemia?
mild-to-moderate: sweating; tremor; tachycardia; hunger; nausea; general sensation of weakness
severe: confusion; altered behavior; difficulty speaking and disorientation, can progress to seizure and coma
What are common strategies used to manage mild, moderate and severe hypoglycemia?
mild-mod: give 15 g of glucose [3/4 cup of juice will raise blood glucose by 2mmol/L within 20 minutes
severe: if conscious, administer 20 g of glucose orally
unconscious: 1 mg of glucagon IM/Sc
If IV access available: 20-50 ml of 50% dextrose IV over 1-3 minutes
What are metformin’s prescribing considerations?
first choice in newly diagnosed w/uncomplicated T2DM
lowers HbA1c by 1-1.5%
improves CV risks
considerably safe to use in STABLE heart failure and liver disease
can be used upto CrCl of >30 ml/min
should be held pre-operatively and when using imaging contrast agents to avoid renal failure and lactic acidosis
What are Alpha-glucosidase inhibitors (ACARBOSE) prescribing considerations?
not available in Canada
significant GI side effects
requires TID dosing
lowers HbA1c% by <1%
What are DPP-4 inhibitors prescribing considerations?
not in patients with HEART FAILURE
lowers HbA1c% by <1%
low risk of hypoglycemia
added as 2nd or 3rd line agent when BG still uncontrolled with metformin
What are GLP-1 agonists prescribing considerations?
when administered SubQ, increase GLP-1 action by 5X
increase insulin secretion
suppress glucagon secretion during post prandial period
slow gastric emptying
increase satiety
lowers HbA1c to a greater extent
Semaglutide associated with 3% increase in diabetic retinopathy
NOT for patients with heart rhythm disturbance; not for pregnant ladies; not for patients with thyroid carcinoma or multiple endocrine neoplasms
What are the prescribing considerations for insulin secretagogues (sulfonylureas and meglitinides)?
SUs: lower HbA1c% by 1-1.5%
Glyburide has great risk of hypoglycemia, and not recommended in elderly and those with renal impairment
Meglitinides: repaglinide and nateglinide
taken just prior to meals, lower HbA1c to a similar extent as SU
can be skipped if meal won’t be taken
lower risk of hypoglycemia compared to SU
What are the prescribing considerations for sodium-glucose co-transporter 2 inhibitors?
cause weight loss
small decrease in BP
low risk of hypoglycemia
NOT in those with reduced GFR
cause mycotic genital infections, volume depletion, urinary tract infection, diabetic ketoacidosis
CANA: increased risk of lower extremity amputation and risk of fracture
EMPA: CV good effect
What are the prescribing considerations for TZDs (rosiglitazone and pioglitazone)?
enhanced insulin sensitivity increased peripheral glucose uptake enhanced fat cell sensitivity to insulin decrease hepatic glucose output risk of hypoglycemia is very low mean decrease in HbA1c is 1-1.5% cause heart failure due to increased SubQ fat deposition, fluid retention and edema worsen macular edema increase risk of wrist and hip fracture ROSIGLITAZONE: increased risk of MI PIOGLITAZONE: increase risk of bladder cancer With both, ovulation resumes with previously un-ovulating women
What factors are taken into consideration when initiating therapy in people with T2DM?
if HbA1c < 1.5% above their personalized target, initiate non-pharmacologic therapy only, if target not met within 3 months, start METFORMIN
if HbA1c > 1.5% above their personalized target, start medications immediately:
1- combo of MF with another agent
2- bedtime insulin may be considered, if so, either start with 5-10 U or 0.1-0.2 U/kg
3- Once meal time insulin is added, need to discontinue oral anti-hyperglycemic meds with the exception of metformin
4- if glycemic values are extremely high on initial presentation, then start immediately with insulin, 0.5 U/kg/day, of which 40% will be given as basal and 60% as short acting divided on 3 meals, if NPH insulin to be started, then 2/3 of daily insulin to be started before breakfast and 1/3 before dinner. ADJUST dose to reach FPG of <7 mmol and 2-hr post prandial glucose <10 mmol
HbA1c target needs to be reached within 3-6 months
Which anti-hyperglycemic agents considered to be safe during pregnancy and breastfeeding?
pregnancy: glyburide; insulin; metformin
to prevent pre-eclampsia, women with pre-existing diabetes should start ASA 81 mg daily at 12-16 weeks’ gestation
Breastfeeding: glyburide; insulin; metformin
Which anti-hyperglycemic agents with evidence of reducing incidence of T2DM?
rosiglitazone
metformin
acarbose
orlistat
