Non-Sulfonylureas

Insulin Sensitizers

Direct Acting

Biguanides: Metformin

- Metformin acts by decreasing the hepatic production of glucose from glycogen, decreases the absorption of glucose by the small intestine, increases insulin sensitivity, and increases glucose uptake and use by fat and skeletal muscles

- Metformin is 51-60% bioavailable and primarily absorbed in the small intestine

- It does not undergo hepatic metabolism and is unchanged in the urine Metformin is the first choice medication with DM2

- When metformin is combined with Sulfonylureas, the drug is useful in cases that are resistant to oral antidiabetics

- It does not undergo hepatic metabolism and remains unchanged in urine

Complications

- GI issues

- Constipation/Diarrhea

- Nausea/Vomiting

- Heartburn

- B12 and folate deficiency

- Caused by altered absorption

- Provide supplementation

- Lactic acidosis

- Symptoms:

- Hyperventilation

- Myalgia/Sluggishness

- Excessive sleepiness

- Severe lactic acid can be treated with hemodialysis

- Patients with renal insufficiency should not take metformin because of the risk for toxic drug accumulation

Thiazolidinediones

Thiazolidinediones discussed bot end with the suffix "-***litazone***"

- Drugs decrease insulin resistance and improve blood glucose control

- Pioglitazone and rosiglitazone are both contraindicated in stage III and IV Heart Failure due to dose-related fluid retention

- Pioglitazone can be combined with [[Sulfonylureas]]

- Rosiglitazone can be combined with metformin

- TZDs do not cause hypoglycemia

- Use with insulin can lead to fluid retention

Complications

- Fluid retention

- Edema

- Weight gain

- Monitor indications of [[Heart Failure]]

- Elevation in LDL levels

- Hepatotoxicity

- Perform baseline and routinely liver function tests (LFTs)

- Monitor signs of hepatotoxicity

- Jaundice or dark urine

- Ovulation in premenopausal women

Nutritional Inhibitors

Absorption

Alfa-Glucosidase Inhibitors: Acarbose and Miglitol

Acarbose and Miglitol do not cause hypoglycemia on their own but can when paired with [[Sulfonylureas]] or [[Insulin]]

- Inhibits alfa-glucosidase in the small intestine which is responsible for releasing glucose from complex carbs

- Delays complex carb absorption

- Acarbose is the prototype drug

- Acarbose has no systemic effects and is not absorbed into the body in significant concentrations

- Used for patients who cannot control their blood glucose with diet alone

Complications

- GI problems

- Diarrhea/Flatulence

- Abdominal pain/Cramping

- Hyperactive bowel sounds

- Anemia

- Due to decreased iron absorption

- Monitor hemoglobin and iron levels

- Hepatotoxicity with long-term use

- Have baseline and routine LFT

- Function returns to normal after medication discontinuation

- Decreased sucrose metabolism

- Increased risk for hypoglycemia

- Use glucose to treat hypoglycemia

- 15g/15 minute reassessment for mild hypoglycemia

- Glucagon for severe

Pramlintide

- Suppresses glucagon secretions, slows gastric emptying, and modulates satiety and appetite

- Can be used for type 1 or type 2 patients

Complications

- GI distress

- Nausea/Vomiting

- Anorexia

- Abdominal pain

- Dizziness

- Fatigue

- Hypoglycemia

Excretion Enhancers

Sodium-Glucose Co-Transporter Inhibitors

Medications have the suffix "-flozin"

- Non-insulin antidiabetics

- Prototype drug is canagliflozin

- Examples of SGLT-2 Inhibitor drugs are Farxiga and Jardiance

- Prevents the reabsorption of glucose from urine

Complications

- UTIs/Vaginal infections

- Renal failure/[[Hyperkalemia]]

- Hypotension/Hypoglycemia

Insulin Stimulators

Direct Acting

Meglitinides

Meglitinides end with suffix "-***glinide***"

- Meglitinides simulate beta cells to release insulin and are short-acting drugs

- Repaglinide is the prototype drug

- The action of meglitinides is similar to [[Sulfonylureas]]

- Meglitinides can be combined with metformin

- Repaglinide and Nateglinide should not be given to patients with liver dysfunction because decreased metabolism rate can lead to hypoglycemic reactions

Complications

- Hypoglycemia

- GI issues

- Nausea

- Diarrhea

- Weight gain

- Respiratory issues

- Infection

- Runny nose

- Arthralgia

Indirect Acting (Incretin Pathway)

Incretin Modifiers

These drugs end with the suffix "-gliptin"

- Also known as dipeptidyl peptidase (DPP-4) inhibitors and gliptins

- Sitagliptin is the prototype drug

- These drugs increases incretin (hormones that stimulate decreases in blood glucose) levels, increases insulin secretions, and decreases glucagon secretions

- It is used as a supplementary treatment to exercise and diet

- Reduces fasting and after-meal blood glucose levels

- Taking sitagliptin with [[Insulin]], glyburide, glipizide, glimepiride can increaser the risk of hypoglycemia

Complications

Generally tolerated well

- GI problems

- Nausea

- Diarrhea

- Stomach pain

- Flu-like symptoms

- Headache

- Runny nose

- Sore throat

- Skin reactions

- Rashes

- Dizziness

- Fever

GLP1-Receptor Agonists

- The prototype drug is semaglutide

- Concurrent use with drugs that increase insulin secretions ([[Sulfonylureas]], meglitinides) can increase the risk of hypoglycemia

- Dosage of insulin-secreting drug may need to be decreased

Complications

- Nausea

- Loss of appetite

- Pancreatitis