Type 2 Pharmacotherapy Flashcards by Carlene Oleksyn

How long can you take to get to A1C target with timely adjustment of meds?

3-6 months

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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.

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How long should you try lifestyle before starting pharmacotherapy? Under what A1C?

3 months can try lifestyle. Unless A1C is 1.5 over goal!

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Due to delayed diagnosis, what percentage of type 2 diabetics will already have micro or macrovascular disease present upon diagnosis?

20-50%

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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.

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Do not select two oral agents with similar modes of action. This would include which classes?

DPP4 not with GLP1

Meglitinides not with sulfonylurea

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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.

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What oral drug should be stopped when starting basal insulin?

Pio

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What drugs should be stopped when adding bolus INsulin?

Secretagogues

Metformin should be continued even with intensive basal bolus.

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When should insulin be automatically started in a newly diagnosed type 2?

symptomatic hyperglycemia And OR metabolic decompensation.

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What are the 4 major problems with using PIO?

Heart failure.
Increased fractures.
Bladder cancer risk.
Edema.

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Which 4 classes would it be rare to cause hypo?

GLP1
DPP4
Alpha glucosidase inhibitor
Thiazolidinediones

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What percentage A 1 C reduction on metformin mono therapy?

What CrCl is it contraindicated?

1-1.5% CrCl less than 30

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What percent reduction for adding alpha glucosidase inhibitor?

What ADR limits its use?

0.6%

GI distress

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What % reduction A1C when adding DPP4?

What rare side effect?

List the 3 agents.

0.7% Improved post prandial control

Pancreatitis

Sitagliptin
Saxagliptin
Linagliptin

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What % reduction in A1C when adding GLP1 to metformin?

Rare ADR?
Avoid with what type of cancer?
Most common ADR?

Pancreatitis
Medullary thyroid cancer
Nausea vomitting

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What % reduction A1C will you get when adding insulin to metformin?

0.9-1.1%

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What % A 1C lowering can you get with: 
Sulfonylureas
Meglitinides 
Pioitazone
Orlistat

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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

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What is the mechanism of action of metformin?

Enhances insulin sensitivity in the liver and peripheral tissues by activation of AMP activated protein kinase.

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How common is lactic acidosis?

3/100,000 patient years

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How often should you increase metformin dosing to aid in tolerance?

Every 1 to 2 weeks

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When is metformin contraindicated? 2

1-CrCl less than 30

2- hepatic failure

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What is the max dosing for repaglinide?

4mg qid

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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