Diabetes Non-Insulin Treatments

Two drug classes that can be started if T2DM patient has ASCVD, heart failure, or CKD

GLP-1 agonist or SGLT2 inhibitor

A1C level that requires two drugs to be started at initiation

8.5-10%

When to start insulin initially in T2DM

A1C > 10% or BG >=300

which are preferred for T2DM GLP-1s or insulin

GLp-1s

what cannot be used with a GLP-1 agonist

DPP-4 inhibitor

what cannot be used with insulin

Sulfonylurea

T2DM with ASCVD tx for cardiorenal risk reduction

GLP-1a or SGLT2-I

T2DM with HF tx for cardiorenal risk reduction

SGLT2-I

T2DM with CKD tx for cardiorenal risk reduction

SGLT2-I or GLP-1a

T2DM BG reduction agents

GLP-1a

Tirzepatide

Insulin

Metformin

SGLT2-I

SU

TZD

Intermediate: DPP-4I

T2DM Weight loss agents

Tirzepatide

semaglutide

dulaglutide

liraglutide

Intermediate: GLP-1a SGLT2-I

Neutral: DPP-4I, metformin

Drugs with cardiorenal benefits

GLP-1a: Dulaglutide, Liraglutide, SC Semaglutide

SGLT2-I: Canagliflozin, dapagliflozin, empagliflozin, ertugliflozin

GLP-1 (Glucagon like peptide) agonists MOA

Analogs of hormone GLP-1 which increases glucose dependent insulin secretion, decreases glucagon secretion, slows gastric emptying

Liraglutide brand

Victoza

Saxenda (Weight loss)

Liraglutide dosing

0.6 mg SC daily x 1 week, then increase to 1.2 mg SC daily

Max: 1.8 mg SC daily

Dulaglutide brand

Trulicity

Dulaglutide dosing

0.75 mg SC once weekly

Max: 4.5 mg SC weekly

Semaglutide brand

Ozempic

Rybelsus (Oral)

Wegovy (Weight loss)

Semaglutide SC dosing

0.25 mg once weekly x 4 weeks, then increase to 0.5 mg weekly

Max: 2 mg weekly

Semaglutide PO dosing

3 mg daily

Exenatide brand name

Byetta

Exenatide dosing

5 mcg SC BID

CrCl < 30: Not recommended

Exenatide ER brand

Bydureon

Exenatide ER dosing

2 mg SC once weekly

eGFR < 45: Not recommended

Drug class of tirzepatide

Dual GLP-1 and GIP agonist

Tirzepatide brand

mounjaro

Zepbound (weight loss)

Tirzepatide dosing

2.5 mg SC weekly x 4 wks then increase to 5 mg SC weekly

Max: 15 mg SC weekly

GLP-1a boxed warnings

All (except byetta) risk of thyroid C-cell carcinoma do not use if personal or family hx

GLP-1a warnings

Pancreatitis

Caution with severe GI diseases

Bydureon BCise: Serious injection site reactions

GLP-1a side effects

Weight loss

N/V

Hypoglycemia

Tirzepatide: Increase HR

GLP-1a notes

Byetta and Victoza: Pen needles not provided

Byetta: Give within 60 minutes before meals

Exenatide: NIOSH drug

GLP-1 injections counseling

Inject subcutaneously into abdomen (alternative sites: back of upper arm, outer thigh, upper buttock)

Attach new pen needle for each injection

Press injection button and count 5-10 seconds before removing needle

Rotate injection sites

Dispose of needles in sharps container

Do not store pens with needles attached

SGLT2-I (Sodium-glucose cotransporter 2 inhibitors) MOA

Reduce glucose reabsorption, increase urinary glucose excretion all in proximal renal tubules

Overall decreased BG concentrations

eGFR level that is recommended to use SGLT2-I

=> 20

Canagliflozin brand

Invokana

Dapagliflozin brand

farxiga

Empagliflozin brand

Jardiance

Bexagliflozin brand

Brenzavvy

SGLT2-I warnings

Ketoacidosis (Occurs if BG < 250 mg/dL)

Genital mycotic infections, UTI (urosepsis, pyelonephritis), necrotizing fasciitis (perineum)

Hypotension

AKI

Canagliflozin and bexagliflozin: Increased risk of leg and foot amputations and foot fractures

SGLT2-I side effects

Increase urination and thirst

Canagliflozin: Hyperkalemia risk

what drugs used with SGLT2-I can cause increased risk of intravascular volume depletion (causing hypotension and AKI)

Diuretics

RAAS inhibitors

NSAIDs

what drug class is metformin

Biguanide

metformin MOA

Decreases hepatic glucose production, increases insulin sensitivity, decreased intestinal absorption of glucose

What is the use of metformin dependent on

eGFR

Metformin brand

Fortamet

Glumetza

Glucophage

metformin IR dosing

500 mg daily

Metformin ER dosing

500-1,000 mg daily

Titrate weekly, usual maintenance dose: 1,000 mg BID

Max dose: 2,000-2,500 mg.day

Give with meal to avoid upset stomach

Metformin boxed warning

Lactic acidosis: risk increased with renal impairment, contrast dye, excessive alcohol

Metformin contraindications

eGFR < 30

metabolic acidosis (includes DKA)

Metformin warnings

Not recommended to start if eGFR 30-45

Vitamin B12 deficiency: (monitor q 1-2 yrs)

Metformin side effects

GI: diarrhea, nausea

Metformin benefits

Decreases A1C 1-2%

Weight neutral

No hypglycemia

What can using metformin with iodinated contrast cause

renal dysfunction

Increased risk of lactic acidosis

Metformin protocol when using iodinated contrast

Discontinue metformin prior to imaging

Restart metformin 48 hrs after procedure

2 drug classes known as insulin secretagogues due to stimulating insulin secretion to decrease post-prandial BG

Sulfonylureas

Meglitinides

MOA of sulfonylureas and meglitinied

Stimulate insulin secretion from pancreatic beta cells to decrease postprandial BG

Do sulfonylureas or meglitinides have a faster onset and shorter duration of action

meglitinides

Sulfonylureas

Glipizide

Glyburide

Glimepiride

Glipizide brand

glucotrol XL

Glimepiride brand

Amaryl

Micronized glyburide brand

glynase

Sulfonylureas contraindications

sulfa allergy

Sulfonylureas warnings

Hypoglycemia

Sulfonylureas A1C effect

Decrease by 1-2%

Glipizide IR administration

take 30 min before a meal, all other sulfonylureas taken with breakfast, hold if NPO

What can Glucotrol XL leave in the stool

ghost tablet

why are sulfonylureas on the beers criteria

hypoglycemia risk

2 meglitinides

repaglinide

Nateglinide

When to take Repaglinide

Take within 30 min before meal

When to take Nateglinide

Take 1-30 min before meals

Meglitinides warnings

Hypoglycemia

Caution with sever liver/renal impairment

Meglitinides side effects

Weight gain

Meglitinides dosing when meals skipped

skip dose

Why should insulin combined with either SU or meglitinides be avoided

hypoglycemia risk

DPP-4 (Dipeptidyl peptidase 4) inhibitors MOA

Prevent the enzyme DPP-4 from breaking down incretin hormones

Regulate BG levels by increasing glucose dependent insulin secretion and decreasing glucagon secretion

Overall increases insulin secretion and decreased glucose production

DPP-4 inhibitors

Sitagliptin

Linagliptin

Saxagliptin

Alogliptin

Sitagliptin brand

Januvia

Linagliptin brand

tradjenta

Linagliptin renal deficiency dosing

No renal dose adjustments

DPP-4 inhibitors warnings

Pancreatitis

Severe arthralgia

Acute renal failure

Saxagliptin and alogliptin: Risk of HF

Thiazolidinediones (TZDs)

Pioglitazone

Thiazolidinediones (TZDs) MOA

Peroxisome proliferator-activated receptor gamma agonist that increases peripheral insulin sensitivity

Pioglitazone brand

Actos

TZDs boxed warning

Can cause HF

Do not use with NYHA Class III/IV HF

TZDs warnings

Edema

Risk of fracture

Hepatic failure

Can stimulate ovulation

TZDs side effects

Peripheral edema

Weight gain

Alpha-Glucosidase inhibitors

Acarbose

Miglitol

Alpha-glucosidase inhibitors administration

Take with the first bite of meal

How to treat hypoglycemia if patient is on a alpha-glucosidase inhibitors

Cannot be treated with sucrose, need glucose tablets or gel

Bile acid binding resins

Colesevelam (Welchol)

Colesevelam SE

constipation

Dopamine agonist

Bromocriptine

Amylin analog

Pramlinitde (symlin)

Pramlintide for T1 or T2DM?

Both

How to solve significant hypoglycemia risk created by Pramlintide if also on insulin

decrease insulin dose by 50% when starting

What is the metformin + TZD combo

metformin/pioglitazone (Actoplus Met)

What is the metformin + DPP-4 inhibitor combo

metformin/sitagliptin (Janumet)

What is the metformin + SGLT2-I combo

metformin/canagliflozin (Invokamet)