Endo 1 Diabetes Agents Table

What medication is a biguanide?

Metformin

What is the MOA of biguanides?

Decrease hepatic glucose production (gluconeogenesis)

Increase peripheral insulin sensitivity

What route are biguanides administered by?

Oral

Pros of biguanides

High efficacy

No hypoglycemia

Weight loss

Inexpensive

What effect do biguanides have on weight?

Weight loss

Side effects of biguanides

GI side effects

B12 deficiency

Lactic acidosis (rare)

Monitoring for biguanides

eGFR

GI side effects (diarrhea, cramping, nausea)

CBC or B12

Lactic acidosis

How can GI side effects associated with biguanides be managed?

Usually self limiting

Take with food, ER formulations, gradual dose titrations, persistence

B12 deficiency associated with biguanides can lead to _____

Macrocytic anemia

Dosing of metformin IR

Initial: 500 mg QD or BID; Increase by 500 mg qwk as tolerated to max effective dose of 1000 mg BID; Max dose: 2550 mg/day

Dosing of metformin ER

Initial: 500 mg QPM; Increase by 500 mg/day qwk; Max dose: 2000 mg/day

Metformin should be discontinued at an eGFR of _____

<30 mL/min

Metformin should not be initiated at an eGFR of _____

<45 mL/min

Why must metformin be stopped if the eGFR is too low?

To prevent lactic acidosis

If a patient is undergoing a procedure using iodinated contrast dye, their metformin should be _____ and their _____ should be rechecked

Held for 48 hours prior; Renal function

Why is it important to hold metformin before procedures involving iodinated contrast dye?

Iodinated contrast dye is hard on the kidneys and causes a temporary decrease in kidney function, which can lead to lactic acidosis with this drug

In addition to diabetes, metformin is also used in which two conditions?

PCOS and prediabetes

While it does not cause kidney problems, metformin causes _____ in patients with renal impairment

Lactic acidosis

What is the MOA of sulfonylureas?

Stimulates insulin secretion from the pancreas

What medications are sulfonylureas?

Glimepiride

Glipizide

Glyburide

What route are sulfonylureas administered by?

Oral

Pros of sulfonylureas

High efficacy

Inexpensive

Cons of sulfonylureas

Hypoglycemia

Weight gain

What effect do sulfonylureas have on weight?

Weight gain

What is an important counseling point for patients to avoid hypoglycemia while taking sulfonylureas?

Patient should not skip meals

Monitoring for sulfonylureas

Renal function

Rash

Decreased renal function caused by sulfonylureas increases the patient’s risk for _____

Hypoglycemia

Which sulfonylurea is not recommended due to having a higher hypoglycemia risk than other agents in its class?

Glyburide

When should sulfonylureas be administered?

With breakfast (or 30 minutes before breakfast for glipizide IR)

Unlike the other sulfonylureas, glyburide should not be used if the eGFR is _____

<60 mL/min

Sulfonylureas display _____ over time (~5 years) due to loss of ß cells

Loss of efficacy

What drug is a thiazolidinedione?

Pioglitazone

What is the MOA of thiazolidinediones?

Increase peripheral insulin sensitivity

Decrease hepatic glucose

What route are thiazolidinediones administered by?

Oral

Pros of thiazolidinediones

High efficacy

No hypoglycemia

Inexpensive

Cons of thiazolidinediones

Weight gain

Edema

Worsens heart failure

Side effects of thiazolidinediones

Bone fractures

Bladder cancer

Monitoring for thiazolidinediones

AST/ALT

Weight/fluid retention (especially with decreased renal function)

What type of bone fractures are caused by thiazolidinediones?

Atypical bone fractures due to precursor cells becoming adipocytes instead of bone cells

• Fatty deposits in bone

When should pioglitazone be used with caution?

Hepatic dysfunction, ALT > 2.5x

Pioglitazone has a black box warning for _____

NYHA Class 3/4 CHF

Pioglitazone, Ozempic, and Mounjaro all have proven benefit in _____

MASH

What medications are DPP4 inhibitors?

Sitagliptin

Linagliptin

Alogliptin

Saxagliptin

What is the MOA of DPP4 inhibitors?

Prevent incretin breakdown, which increases glucose-dependent insulin release

What route are DPP4 inihibitors administered by?

Oral

Pros of DPP4 inhibitors

No hypoglycemia

Well tolerated

Cons of DPP4 inhibitors

Not very effective

Expensive

Why do DPP4 inhibitors and GLP-1RAs not cause hypoglycemia?

They only increase the release of insulin when glucose is present

Side effects of DPP4 inhibitors

Joint pain, pancreatitis, urticaria, angioedema

• All are rare

Monitoring for DPP4 inhibitors

eGFR

Pancreatitis

What is a typical presentation of pancreatitis?

Pain in the abdomen that radiates into the back

All of the DPP4 inhibitors require renal dose adjustments except for _____

Linagliptin

Which two DPP4 inhibitors worsen HF unlike the other agents in this class?

Alogliptin and Saxagliptin

Dosing of Sitagliptin

100 mg QD

eGFR 30-45 - 50 mg QD

eGFR < 30 - 25 mg QD

Dosing of Linagliptin

5 mg QD

When should DPP4 inhibitors be used with caution?

Pancreatitis

DPP4 inhibitors cannot be used with which other drug class?

GLP1RAs

Which DPP4 inhibitor has an interaction with inducers of CYP3A4 and PGp?

Linagliptin

What is an important counseling point on the administration of DPP4 inhibitors?

Do not crush, swallow whole

What medications are SGLT2 inhibitors?

Canagliflozin

Dapagliflozin

Empagliflozin

Ertugliflozin

Bexagliflozin

What is the MOA of SGLT2 inhibitors?

Reduces glucose reabsorption

Increases urinary excretion

What route are SGLT2 inhibitors administered by?

Oral

Pros of SGLT2 inhibitors

No hypoglycemia

Weight loss

Cons of SGLT2 inhibitors

Not very effective

Expensive

Side effects of SGLT2 inhibitors

Genitourinary infections, fractures, AKI, dehydration, hypotension, DKA, increased LDL

While they are beneficial in CKD, SGLT2 inhibitors can cause AKI due to _____

Dehydration

SGLT2 inhibitors can cause a unique type of DKA known as _____

Euglycemic DKA

• DKA without elevated blood sugar

SGLT2 inhibitors can cause hypotension due to _____

Hypovolemia

Monitoring for SGLT2 inhibitors

eGFR

BP

Which SGLT2 inhibitor requires renal dose adjustment?

Canagliflozin

Dosing of canagliflozin

100 mg QAM, titrate to 300 mg QAM

eGFR < 60 - 100 mg QAM

Dosing of dapagliflozin

5 mg QAM, titrate to 10 mg if needed

Dosing of empagliflozin

10 mg QAM, titrate to 25 mg if needed

When should SGLT2 inhibitors be used with caution?

Hypotension (higher risk in elderly, renal impairment, hypovolemia, ACEI/ARB/diuretics)

Urosepsis/pyelonephritis

Fournier’s Gangrene

SGLT2 inhibitors should be held for _____ before surgery due to risk of DKA

3 days

Which two SGLT2 inhibitors should be avoided in patient’s with any history of amputation?

Canagliflozin and Bexagliflozin

When should SGLT2 inhibitors be taken?

In the morning before first meal

While SGLT2 inhibitors are less effective at lowering A1C when eGFR < 45, they are still used for their CKD benefits as long as the eGFR is above _____

20 mL/min

What medications are GLP1RAs?

Semaglutide

Dulaglutide

Liraglutide

Exenatide

Lixisenatide

What is the MOA of GLP1RAs?