Oral and Non-Insulin Injectable Medications

non-pharmological interventions for diabetes

1. Exercise

- Burn sugar through exercise

2. Diet

- Decrease the amount of carbohydrates consumed

Motivational Interviewing

Meeting patient where they are at & coach them on where to improve

- Open Questions

- Exchange of Information

- Affirmation

- Attending to the language of change

- Reflections

- Summarizing

Medical Nutrition Therapy

Healthy meal plan that is moderate in calories and carbohydrates recommended

+ Carbohydrate counting

- Decrease added sugars

- Increase Non starchy vegetables

Medical Nutrition Therapy: The Plate Method

9 Inch Plate

1/2 filled with non-starchy vegetable

1/3 filled with carbohydrate source

1/3 filled with lean protein source

Physical Activity recommended for diabetic patients

150 minutes/week of physical activity

- 50-70% of maximal heart rate

- Resistance/strength training at least 2 times/week

Biguanides Drugs

Metformin and Metformin XR

Metformin Brand Name

Glucophage

Starting a patient on Metformin

Start with XR & take at nighttime with food to DEC GI AEs

Metformin (Biuganides) AEs

- Gastrointestinal side effects common (diarrhea, nausea)

- Potential for B12 deficiency (after long term use)

Metformin is _______________ dosed

renally

Metformin consideration with renal impairment

Contraindicated in patients with GFR < 30

- Initiation not recommended in GFR 30-45 and should be at 50% reduced dose

- Risk for lactic acidosis

The ____________ formulation of Metformin tends to have less GI side effects

XR

metformin effect on weight

weight neutral or weight loss

Does metformin have benefit in ASCVD

potential

Does metformin have benefit in HF

no

Does metformin cause hypoglycemia

No

Metformin decreases hepatic glucose production, insulin sensitivity enhanced at peripheral muscle

Sulfonylureas Drugs

- glimepiride

- glipizide

- glipizide XR

- glyburide

glimepiride brand

amaryl

glipizide brand

Glucotrol

glyburide brand

Glynase

All _____________ have poor long term durability

Sulfonylureas (SU)

________________ should be avoided in older adults

Sulfonylureas (SU)

Do Sulfonylureas (SU) cause hypoglycemia

yes

Glyburide is the worst of SU

Sulfonylureas (SU) effect on weight

weight gain --> due to insulin secretion

Which drugs show benefit in HF

SGLT-2 Inhibitors

- canagliflozin (Invokana)

- dapagliflozin (Farxiga)

- empagliflozin (Jardiance)

- ertugliflozin (Steglatro)

Which drugs show increased risk in HF

Thiazolidinediones (TZDs)

- pioglitazone

- rosiglitazone

Potential risk in DDP-4 Inhibitors (saxagliptin)

Which drugs cause weight gain

Thiazolidinediones (TZDs)

- pioglitazone

- rosiglitazone

Sulfonylureas (SU)

- glimepiride

- glipizide

- glipizide XR

- glyburide

- Insulin

Which drugs cause weight loss

SGLT-2 Inhibitors

- canagliflozin (Invokana)

- dapagliflozin (Farxiga)

- empagliflozin (Jardiance)

- ertugliflozin (Steglatro)

GLP-1 RAs

- exenatide XR (Bydureon)

- liraglutide (Victoza)

- dulaglutide (Trulicity)

- semaglutide (Ozempic/Rybelsus)

GIP & GLP-1 RAs

- tirzepatide (Mounjaro)

Metformin (potential loss)

Which drugs have no effect on weight

DDP-4 Inhibitors

- alogliptin (Nesina)

- linagliptin (Tradjenta)

- saxagliptin (Onglyz)

- sitagliptin (Januvia)

Which drugs cause hypoglycemia

Sulfonylureas (SU)

- Glyburide is the worst of SU

All Insulin

- Rapid acting has more incidence of hypoglycemia

- Long acting has less incidence

Sulfonylureas (SU) MOA

work by enhancing insulin secretion in the !-cells

Sulfonylureas (SU) AEs

hypoglycemia

- glyburide has an active metabolite so much more hypoglycemia

Sulfonylureas (SU) directions for use

- Taken with meals

- Avoid in older adults

- Administer 30 minutes before a meal (preferably before breakfast if once-daily dosing)

Which drugs show benefit in ASCVD

- metformin (potential)

- empagliflozin

- canagliflozin

- dulaglutide

- liraglutide

- semaglutide (SQ)

Highest Efficacy Diabetes Medication

Insulin

High Efficacy Diabetes Medications

metformin

GLP-1 RA

- exenatide XR (Bydureon)

- liraglutide (Victoza)

- dulaglutide (Trulicity)

- semaglutide (Ozempic/Rybelsus)

Thiazolidinediones (TZDs)

- pioglitazone

- rosiglitazone

Sulfonylureas (SU)

- glimepiride

- glipizide

- glipizide XR

- glyburide

Intermediate Efficacy Diabetes Medications

SGLT-2 Inhibitors (SGLT2i)

- canagliflozin (Invokana)

- dapagliflozin (Farxiga)

- empagliflozin (Jardiance)

- ertugliflozin (Steglatro)

Dipeptidyl Peptidase-4 Inhibitors (DPP4i)

- alogliptin (Nesina)

- linagliptin (Tradjenta)

- saxagliptin (Onglyza)

- sitagliptin (Januvia)

Diabetes Medications with Renal Benefit

Diabetic Kidney Disease Progression

- empagliflozin

- canagliflozin

- dapagliflozin

Diabetes Medications that need more data on Renal Outcomes

- dulaglutide

- liraglutide

- semaglutide (SQ)

Thiazolidinediones Drugs

- pioglitazone

- rosiglitazone

pioglitazone brand

Actos

rosiglitazone brand

Avandia

Thiazolidinediones (TZDs) AEs

- Edema

- New onset or worsening HF (contraindicated in NYHA Class III or IV)

- Weight gain

- ⬆Bone fractures

- Bladder cancer (pioglitazone)

- ⬆LDL

What drug causes bladder cancer

pioglitazone

Thiazolidinediones (TZDs) MAO

TZDs enhance insulin sensitivity at muscle, liver and fat tissues

Thiazolidinediones (TZDs) Contraindications

new onset or worsening HF

Thiazolidinediones (TZDs) effect on weight

weight gain

Do Thiazolidinediones (TZDs) cause hypoglycemia

no

Dipeptidyl peptidase-4 Inhibitors (DPP-4i) Drugs

- alogliptin (Nesina)

- linagliptin (Tradjenta)

- saxagliptin (Onglyza)

- sitagliptin (Januvia)

alogliptin brand

Nesina

linagliptin brand

Tradjenta

saxagliptin brand

Onglyza

sitagliptin brand

Januvia

Dipeptidyl peptidase-4 Inhibitors (DPP-4i) MOA

Inhibits DDP-4 responsible for degradation of GLP-1 and GIP

- Increase in glucose-dependent insulin secretion, reduction in glucagon secretion

Dipeptidyl peptidase-4 Inhibitors (DPP-4i) Efficacy

Intermediate efficacy

Doesn't work very well because diabetic patients do not have much GLP-1 & GIP to begin with

Dipeptidyl peptidase-4 Inhibitors (DPP-4i) Contraindications

- Heart failure (saxagliptin and alogliptin)

- Pancreatitis

Dipeptidyl Peptidase-4 Inhibitors (DPP4i) Renal Dose Adjustments

Renal dose adjustments in sitagliptin, saxagliptin and alogliptin

*NOT in linagliptin

Dipeptidyl peptidase-4 Inhibitors (DPP-4i) AEs

Extremely well tolerated

- Joint pain

Don't combine Dipeptidyl peptidase-4 Inhibitors (DPP-4i) with _________

GLP-1

- exenatide XR (Bydureon)

- liraglutide (Victoza)

- dulaglutide (Trulicity)

- semaglutide (Ozempic/Rybelsus)

Dipeptidyl peptidase-4 Inhibitors (DPP-4i) cause hypoglycemia

no

Dipeptidyl peptidase-4 Inhibitors (DPP-4i) effect on weight

weight neutral

Sodium-glucose transporter-2 Inhibitor (SGLT-2i) Drugs

- canagliflozin (Invokana)

- dapagliflozin (Farxiga)

- empagliflozin (Jardiance)

- ertugliflozin (Steglatro)

canagliflozin brand

Invokana

dapagliflozin brand

Farxiga

empagliflozin brand

Jardiance

ertugliflozin brand

Steglatro

Sodium-glucose transporter-2 Inhibitor (SGLT-2i) MOA

cause glucose secretion in the kidneys

- causes us to excrete sugar in urine to reduce blood sugar

Sodium-glucose transporter-2 Inhibitor (SGLT-2i) Side Effects

- euglycemic ketoacidosis

- Risk of bone fracture (canagliflozin)

- Lower limb amputation (canagliflozin)?

- Genitourinary infections

- Risk of volume depletion - Hypotension

- LDL

- Risk of Fournier's gangrene

What drug class causes euglycemic ketoacidosis

Sodium-glucose transporter-2 Inhibitor (SGLT-2i)

Do Sodium-glucose transporter-2 Inhibitor (SGLT-2i) show benefit in HF

Yes

- canagliflozin (Invokana)

- dapagliflozin (Farxiga)

- empagliflozin (Jardiance)

NOT ertugliflozin (Steglatro)

Sodium-glucose transporter-2 Inhibitor (SGLT-2i) renal outcomes

canagliflozin and dapagliflozin are shown to prevent renal disease

Sodium-glucose transporter-2 Inhibitor (SGLT-2i) effect on weight

weight loss

Do Sodium-glucose transporter-2 Inhibitor (SGLT-2i) cause hypoglycemia

No

GLP-1

- Glucagon like peptide 1 - Secreted from the small intestine after a meal

- increases insulin secretion

- inhibits glucagon secretion

- signals satiety in the CNS

- delays gastric emptying

Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) Drugs

- exenatide XR (Bydureon)

- liraglutide (Victoza)

- dulaglutide (Trulicity)

- semaglutide (Ozempic/Rybelsus)

Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) MAO

stimulate insulin secretion in glucose dependent manner, reduces hepatic glucose output, slows gastric emptying, increase satiety

- Provides doses of GLP-1 6-10 times natural levels

Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) AEs

- GI (nausea, vomiting, diarrhea)

● GI side effects are dose related so we titrate up the dose

● Weekly formulations tend to have less of GI side effects

- Associated with pancreatitis

- Weight loss

- Suicidal thoughts or actions?

Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) Contraindications

- Avoid exenatide if GFR < 30

- Contraindicated in pts with history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2

Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) effect on weight

Weight loss

- liraglutide (Victoza) &semaglutide (Ozempic/Rybelsus) available at higher doses as weight loss medication

Do Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) cause hypoglycemia

No

Avoid exenatide if

GFR < 30

Do Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) show ASCVD benefit

- liraglutide (Victoza)

- dulaglutide (Trulicity)

- semaglutide (Ozempic)

Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) administration

subcutaneous

Oral Glucagon-Like Peptide-1 Receptor Agonists

semaglutide (Rybelsus)

semaglutide (Rybelsus) AEs

Same GI side effects as injection formulation

- Abdominal pain (~10%)

- Nausea (~10-20%)

Glucose-Dependent Insulinotropic Polypeptide (GIP)/Glucagon-Like Peptide (GLP-1) Receptor Agonist Drugs

tirzepatide (Mounjaro)

What medications are renally dosed

Metformin

Dipeptidyl Peptidase-4 Inhibitors (DPP4i)

Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2 i)