Type 2 Pharmacotherapy Flashcards
How long can you take to get to A1C target with timely adjustment of meds?
3-6 months
At what A1C level should you immediately start meds with lifestyle?
> or = 1.5 ABOVE target A1C. Consider starting 2 agents, .
***if symptomatic hyperglyc with metabolic decompensation start insulin +|- metformin!! Ie:the poly’s weight loss or volume depletion.
How long should you try lifestyle before starting pharmacotherapy? Under what A1C?
3 months can try lifestyle. Unless A1C is 1.5 over goal!
Due to delayed diagnosis, what percentage of type 2 diabetics will already have micro or macrovascular disease present upon diagnosis?
20-50%
When will drugs have the greatest ability to lower A1C? When A1C is high or low?
Higher the A1C the greater the degree a drug will lower it. Maximal
Effect of oral therapy is seen at 3-6 months.
The closer you get to target A1C the more post prandial BG levels contribute to the A1C. HOWEVER, targeting post prandial in type 2 had not been shown to reduce macrovascular complication.
Do not select two oral agents with similar modes of action. This would include which classes?
DPP4 not with GLP1
Meglitinides not with sulfonylurea
Is it better to Max dose of one agent before adding a second oral
Agent?
No. You could get suboptimal response of the second agent.
Using submaximum doses of two agents provided much better glycemic control with less side effects.
What oral drug should be stopped when starting basal insulin?
Pio
What drugs should be stopped when adding bolus INsulin?
Secretagogues
Metformin should be continued even with intensive basal bolus.
When should insulin be automatically started in a newly diagnosed type 2?
symptomatic hyperglycemia And OR metabolic decompensation.
What are the 4 major problems with using PIO?
Heart failure.
Increased fractures.
Bladder cancer risk.
Edema.
Which 4 classes would it be rare to cause hypo?
GLP1
DPP4
Alpha glucosidase inhibitor
Thiazolidinediones
What percentage A 1 C reduction on metformin mono therapy?
What CrCl is it contraindicated?
1-1.5% CrCl less than 30
What percent reduction for adding alpha glucosidase inhibitor?
What ADR limits its use?
0.6%
GI distress
What % reduction A1C when adding DPP4?
What rare side effect?
List the 3 agents.
0.7% Improved post prandial control
Pancreatitis
Sitagliptin
Saxagliptin
Linagliptin
What % reduction in A1C when adding GLP1 to metformin?
Rare ADR?
Avoid with what type of cancer?
Most common ADR?
1%
Pancreatitis
Medullary thyroid cancer
Nausea vomitting
What % reduction A1C will you get when adding insulin to metformin?
0.9-1.1%
What % A 1C lowering can you get with: Sulfonylureas Meglitinides Pioitazone Orlistat
- 8%
- 7%
- 8%
- 5%
Which type 2 antihyperglycemics can be used at ANY eGFR? Ie. <15
Repaglinide But watch hypo
Pioglitazine but watch edema
Sitagliptin and Linagliptan (DPP4)
Insulin
*think of Kristeena. Was on repag and lower januvia
What is the mechanism of action of metformin?
Enhances insulin sensitivity in the liver and peripheral tissues by activation of AMP activated protein kinase.
How common is lactic acidosis?
3/100,000 patient years
How often should you increase metformin dosing to aid in tolerance?
Every 1 to 2 weeks
When is metformin contraindicated? 2
1-CrCl less than 30
2- hepatic failure
What is the max dosing for repaglinide?
4mg qid
Allergy to sulfa drugs cross reacts with what class of oral meds?
Sulfonylureas
What is the mechanism of action of TZDs?
Decrease insulin resistance in muscle and liver.
Enhances glucose use
Decreased hepatic glucose output
Why can’t PIO be used with insulin?
Higher risk of CHF and edema.
What is the MOA of acarbose?
Slows the breakdown of complex CHO in the brush border of the intestine. This leads to slower rise in PP BG.
What is the dosing for acarbose?
Do you decrease for renal function?
50mg qd increasing every 1-2 weeks to 50mg tid as tolerated. Can go to 100mg tid
If eGFR less than 30 must stop. No dose adjustments.
Do not use if inflammatory gi conditions.
If a patient is on acarbose, how do you treat hypoglycemia?
Cannot treat with sucrose as cannot break it down. Must be glucose or honey or milk which is a monosaccharide
What are the daily doses used for the four DPP4 inhibitors? And which one needs no dose adjustment until eGFR less than 15? Sita Saxa Lina Alo
Sita 100mg
saxa 5mg
Lina 5mg
Alogl 25mg
Linagliptin
What is the dosing for canagliflozin?
100mg qd. Increase to 300mg qd if needed.
With or without food.
When eGFR < 60 it’s 100mg.
Stop at eGFR <30 as cardiorenal benefits not established beyond this.
What is the dosing of dapagliflozin? Ie: Forxiga
5mg qd. Can increase to 10mg qd if needed/tolerated.
With or without food.
The only SHLT2 that has no glycemic lowering at eGFR <60 so do not use for glycemic.
Though it does offer cardio renal protection
What is the dosing of empagliflozin?
10mg. May increase to 25mg if needed.
With or without food.
At what CrCl would SGLT2s not be effevtive for glycemic lowering (though still used for ckd)
Canagliflozin <45 Empagliflozin <45 Dapagliflozin <60 *strongest evidence for cana for CKD protection Use if >30 for CKD!!
When is it useful to add fenofibrate to statin?
To slow progression of established retinopathy.
Which DPP4 should you be cautious about in heart failure?
Saxagliptin.
Which SGLT2 should not be used if bladder cancer?
Dapagliflozin
Which oral med class can take 6-12 weeks for maximal effect??
Thiazolidinediones
Which class of drugs is contraindicated in medullary thyroid cancer or multiple endocrine neoplasma syndrome?
GLP1
What drugs could you add to Metformin with an eGFR of 64
Any of them
What drugs can you add to metformin if eGFR is in the 40s
Which ones can you add but use a reduced dose?
FIRST. Must reduce metformin to 500-1000mg/ day.
No dose reduction: Repaglinide Acarbose Thiazolidinediones Glic or glimepiride Incretins: Linagliptin ONLY All GLP1s SGLT2 for cardiorenal only
REDUCE DOSE
Lexenatide. Exenatidr.
DPP4s sita and saxa.
What drugs can you add to metformin if eGFR is less than 30??
None. Stop metformin first!!
What drugs can be used at eGFR less than 30?
Acarbose stop at 25!
DPP4s at reduced dose. Except Linagliptin you reduce at 15
GLP1s exc lixenatide and exenatide.
Glic and Glim reduce at 30. Stop at 15
Thiazolidinediones
Repaglinide.
Can any glycemic drugs be used if eGFR is less than 15??
Repaglinide
Glic and glimep at lower doses
DPP4s Sita and Alogliptan
Thiazolidinediones but watch for fluif
Why would you not use genfibrozil in a type two patient?
Interacts with statins, sulfonylureas, repagljnide, ezetrol, PIO, bile acids. Is there anything it doesn’t interact with?
Which 2 classes cause weight gain?
Thiazolidinediones and sulfonylurea
Maximal effect for oral therapy is seen in how long?
3 to 6 months
What three GLP1s have evidence for reduction on MACE in type 2s WITH established CVD
Liraglutide
Semaglutide
Dulaglutide
What GLP 1 has no evidence of CV benefit?
Lixiisenatide
Which GLP1 has the strongest evidence for CV benefit without established CVD.
AND what patient age etc is the recommendation for?
Dulaglutide Age over 60 + at least 2 risk factors Hyperlip BP Smoking Abd obeisity
Which SGLT2 had trial evidence of HF reduction where diabetes was not an inclusion criteria?
Dapagliflozin
Should an SGLT2 be used in eGFR 30-45??
Which had strongest trial evidence?
Yes. Even though <45 it wont contribute to glycemic lowering it will reduce progression of CKD
STRONGEST evidence for Cana. Then Dapa then Empa
Any evidence for DPP4 for reduction of CVD?
No.
Which DPP4 should NOT be used in HF or CVD or in those with risk factors
Saxaglipton
What three classes are associated with weight gain?
TZD
Insulin
Insulin secretagogues
What class is weight neutral?
DPP4
What are the signs of metabolic decompensation where you woukd start insulin right away 3
Unintentional weight loss
Marked or symptomatic hyperglycemia
Ketosis
If a patient is on metformin and basal insulin and not controlled what shoud you add?
GLP1
SGLT2
DPP4
RATHER than strating bolus!!!
Which SU has the least risk of hypo?
Gliclizide
Thiazolidinediones.
Hypo?
Weight gain?
No
Yes
Even if at A1C goal, should a GLP-1 or AGLT2 be started if person has ASCVD. HF. OR CKD?
Yes.
ASCVD. Or CV risk factors and over 60 -> GLP1. Reduces MACE
HF. SGLT2
CKD. SHLT2
What about primary prevention for SGLT2 and GLP-1
Yes but ONLY if risk factors. Ie: >age 60 and two CV risk factors. Smoking. Lipids. BP.
Glp1. For MACE
SGLT2 For HF AND NEPHROPATHY (NOT MACE)
Which SGLT2 does not have any glycemic lowering at <60
Dapagliflozin
