Diabetes Drugs

Biguanides MoA

Metformin decreases hepatic glucose production and intestinal glucose absorption while increasing the sensitivity of cells to insulin.

Available formats include immediate-release (IR) and extended-release (ER) tablets.

What is the Onset, Peak and Duration of Metformin (IR)

Onset: unknown

Peak: unknown

Duration: 12 hours

What is the Onset, Peak and Duration of Metformin (ER)

Onset: unknown

Peak: unknown

Duration: 12 hours

What are some Contraindications to administering Metformin

Hypersensitivity

Metabolic acidosis

Severe renal impairment

Use with iodine-based dyes

Hepatic impairment

Lactation

Side effects of Metformin

Abdominal bloating

Diarrhea

Nausea

Vomiting

Metallic taste

Note: Gastrointestinal side effects are common at the start of therapy and decrease over time.

Adverse effects of metformin

Lactic acidosis

Concurrent use of Metformin with Alcohol or iodated contract media may lead to

increases the risk of lactic acidosis

Concurrent use of Metformin with amiloride, digoxin, morphine, procainamide, quinidine, triamterene, trimethoprim, calcium channel blockers and vancomycin

may decrease the excretion of metformin

Concurrent use of Metformin with nifedipine

increases the absorption and effects of metformin, increasing the risk of lactic acidosis.

Concurrent use of Metformin with glucosamine

will decrease glycemic control, leading to hyperglycemia.

Concurrent use of Metformin with amiloride, cimetidine, furosemide, and chromium or coenzyme Q-10 supplements

may lead to increased hypoglycemic effects.

Sulfonylureas (Glipizide) MoA

Sulfonylureas stimulate the release of insulin from the pancreas while increasing the sensitivity of insulin receptor sites on the cells. Glipizide may also decrease hepatic glucose production.

Onset, Peak, Duration of Glipizide

Onset: 15-30 minutes

Peak: 1-2 hours

Duration: up to 24 hours

Contraindications for Glipizide

Hypersensitivity to sulfonylureas or sulfonamides

Insulin-dependent diabetics

Diabetic coma or ketoacidosis

Side Effects of Glipizide

Photosensitivity

Hypoglycemia

Adverse Reactions of Glipizide

Aplastic anemia

What does taking Glipizide with diuretics, corticosteroids, oral contraceptives, estrogens, progestins, thyroid preparations, and phenytoin.

May decrease the effectiveness of certain medications

What happens when Glipizide is taken with Warfarin, alcohol, ACE inhibitors, angiotensin II receptor blockers, fluoxetine, MAO inhibitors, NSAIDs, and other medications?

increases the risk of hypoglycemia

How does concurrent use of Glipizide and warfarin affect drug response?

It may alter the response to both drugs, initially increasing effects and changing to decreased effects over time.

What should be noted about Glipizide and beta-adrenergic blockers?

They may mask a hypoglycemic reaction; use with caution.

Glinides (Repaglinide) MoA

Like sulfonylureas, glinides increase insulin secretion from the pancreas. Unlike sulfonylureas, glinides have a quicker onset, a shorter duration of action, and must be administered with each meal. Due to the rapid onset of action, the drug should be taken at the start of a meal.

Onset, Peak, Duratoin of Repaglinide (PO)

Onset: 15-60 minutes

Peak: 1 hour

Duration: 4-6 hours

Contraindications of Repaglinide

Hypersensitivity to repaglinide, sulfonylureas, or sulfonamides

Diabetes mellitus type 1

Diabetic coma or ketoacidosis

Side effects of Repaglinide

Hypoglycemia

Headache

Upper respiratory infection

Adverse reactions to Repaglinide

Chest pain

Irregular heartbeat

When are dosage adjustments recommended?

In clients taking concomitant strong CYP3A4 or CYP2C8 inhibitors or inducers.

What should be avoided when taking Repaglinide?

Coadministration with Clopidogrel; if unavoidable, initiate repaglinide at 0.5 mg before each meal, not exceeding 4 mg/day.

What is the maximum daily dose of Cyclosporine when taken alongside Repaglinide?

Do not exceed a total daily dose of 6 mg.

What is contraindicated with the use of Repaglinide?

The use of alcohol.

What reaction may occur when using Repaglinide with sulfonylureas?

A disulfiram-like reaction.

Thiazolidinediones (Pioglitazone)

Thiazolidinediones, or glitazones, target the genes involved with insulin resistance by increasing the sensitivity of insulin receptors on cell membranes. This causes increased peripheral glucose uptake and decreased glucose and triglyceride production in the liver.

Onset,Peak, Duration of Pioglitazone (Oral)

Onset: delayed

Peak: 2 hours

Duration: unknown

Contraindications of Pioglitazone

Symptomatic heart failure (black box warning)

Liver disease

Kidney disease

side effects of pioglitazone

Peripheral edema

Weight gain

Reduced bone mineral density

Bone fractures

Adverse reactions to Pioglitazone

Exacerbation of heart failure

if Pioglitazone is taken with a CYP3A4 inhibitor...

Serum levels of pioglitazone may increase as it is partly metabolized by CYP3A4

Dipeptidyl Peptidase-IV Inhibitors - Sitagliptin MoA

DDP-4 inhibitors block the dipeptidyl peptidase-IV enzyme from destroying incretin, a hormone released by the gastrointestinal (GI) tract, to increase insulin synthesis after eating. By blocking the DPP-4 enzyme, DPP-4 inhibitors reduce postprandial (after meal) serum glucose levels.

Onset, Peak, Duration of Sitagliptin oral tablets

Onset: rapid

Peak: 1-4 hours

Duration: 24 hours

Contraindications of Sitagliptin

Diabetes mellitus type 1

Hypersensitivity

Safety not established during pregnancy, lactation, or in children

side effects of sitagliptin

Headache

Hypoglycemia (if taken with other antidiabetic medications)

adverse effects of sitagliptin

Heart failure

Stevens-Johnson syndrome

Pancreatitis

Rhabdomyolysis

Anaphylaxis and angioedema

Using Sitagliptin with Digoxin may...

Increase digoxin levels

Using Sitagliptin with insulin, glyburide, glipizide or glimepiride poses...

and increased risk of hypoglycemia

Alpha-Glucosidase Inhibitors - Acarbose MoA

Alpha-glucosidase inhibitors mimic the action of several enzymes that break down complex carbohydrates within the gastrointestinal (GI) system, decreasing the amount of glucose available to enter the circulatory system.

Acarbose oral tablets

Onset: 1-1.5 hours

Peak: 2 hours

Duration: 2-3 hours

Contraindications of Acarbose

Known allergy

Diabetic ketoacidosis

Cirrhosis

Inflammatory bowel disease

Colonic ulceration

Partial intestinal obstruction

Chronic intestinal disease

Renal disease

Side effects of acarbose

Abdominal pain

Diarrhea

Flatulence

adverse effects of acarbose

Severe allergic reaction

Pneumatosiscystoidesintestinalis (rare)

Hypoglycemia

When Acarbose is taken with other antidiabetic medications there is...

An increased risk of hypoglycemia

Use Acarbose with caution if it is being used with Pancreatic enzymes because...

it may alter the absoprtion of alpha-glucosidase inhibitors

Sodium Glucose Cotransporter Inhibitors - Empagliflozin MoA

SGLT2 inhibitors block the sodium glucose cotransporter 2 SLGT2 enzyme to decrease glucose reabsorption in the proximal renal tubules, leading to decreased serum glucose levels. They work independently of insulin to prevent glucose reabsorption, which results in glycosuria. They may also increase insulin sensitivity and glucose uptake in the muscle cells and decrease gluconeogenesis.

Onset, Peak, and Duration Empagliflozin oral tablet

Onset: unknown

Peak: 1.5 hours

Duration: unknown

Contraindications of Empagliflozin

Severe renal impairment

Type 1 diabetes mellitus and diabetic ketoacidosis

Lactation

Side effects of Empagliflozin

Hypotension

Volume depletion

Increased urination

Urinary tract infections

Genital yeast infections

Adverse reactions of Empagliflozin

Ketoacidosis

Necrotizing fasciitis of perineum

Urosepsis

When Empagliflozin is taken along with Antihypertensives or Diuretics

it increases the risk of hypotension

When Empagliflozin is taken along with other antidiabetics

there is an increased risk of hypoglycemia

When Empagliflozin is taken along with diuretics, ACE inhibitors, angiotensin receptor blockers, or non-steroidal anti-inflammatory drugs it...

increased risk of kidney injuries

When Empagliflozin is taken concurrently it...

May decrease lithium levels and effectiveness

Amylin Agonists - Pramlintide MoA

An amylin agonist mimics the action of amylin produced by the body.

Amylin is an endogenous hormone secreted with insulin that decreases postprandial serum glucose levels by slowing gastric emptying, suppressing hepatic glucose production and release of glucagon, and increasing satiety (feeling of fullness).

Onset, Peak, Duration of Pramlintide subcutaneous injection

Onset: rapid

Peak: 20-30 minutes

Duration: 3 hours

Contraindications of Pramlintide

Gastroparesis

Concurrent use of drugs that alter gastric motility

Pregnancy category C

side effects of pramlintide

Nausea

Headache

Vomiting

Severe hypoglycemia

adverse effects of pramlintide

None known

When Pramlintide is used with other antidiabetic medications

Administer cautiously

When Pramlintide is used with oral medications it may

Delay absorption due to delayed gastric emptying

When Pramlintide is used with preprandial rapid- or short-acting insulin

can potentially cause hypoglycemia and the insulin dose usually needs to be reduced by 50%

Glucagon-Like Peptide-1 Agonists - Liraglutide MoA

Acts like GLP-1 to increase insulin release when glucose increases, supporting euglycemia

Decreases glucagon secretion

Delays gastric emptying and suppresses appetite

Glucagon-like peptide-1 (GLP-1) agonists, also referred to as incretin mimetics, act like incretin to enhance glucose-dependent insulin secretion, decrease postprandial glucose production, and decrease gastric emptying.

Onset, Peak, Duration Liraglutide subcutaneous injection

Onset: within 4 weeks

Peak: within 8 weeks

Duration: unknown

Note: Onset, peak, and duration refer to decrease in hemoglobin A1C levels, not drug levels.

Contraindications of Liraglutide

Hypersensitivity

Gastroparesis (Petri et al., 2021)

History of medullary thyroid cancer (personal or family)

Weight loss during pregnancy

Lactation

Safety and efficacy not established in children < 12 years

Side effects of Liraglutide

Hypoglycemia

Diarrhea

Nausea and vomiting

adverse effects of Liraglutide

Thyroid C-cell tumors

Pancreatitis

Suicidal behavior/ideation

When Liraglutide is used alongside Agents that increase insulin secreation like sulfonylureas and insulin it...

May increase the risk of serious hypoglycemia

When Liraglutide is used with any oral medication

It may alter the absorption rate of the oral medication do to delayed gastric emptying