Pancreatic Hormones & Antidiabetic Drugs/Diabetes Management

Diabetes goals of treatment

• Near-normalization of blood glucose (helps prevent microvascular complications)

• Prevention of acute complications such as hypoglycemia

• Prevention of disease progression to target organ damage

• Appropriate patient-oriented self-management

Treatment targets include glucose/HgbA1c, BP, and lipids.

Prevent complications: ACEI, statin, aspirin

Insulin

Essential for utilization of glucose by all body cells

Insulin mechanism of action:

Binds to receptors on the cell membrane and facilitates transport of glucose into the cell for energy

• Increases storage of glucose as glycogen (glycogenesis) in muscle and liver cells

• Inhibits glucose production in liver and muscle cells (glycogenolysis)

• Promotes protein synthesis by increasing amino acid transport into cells

• Enhances fat storage (lipogenesis) and prevents mobilization of fat for energy (lipolysis and ketogenesis)

• Inhibits glucose formation from noncarbohydrate sources, such as amino acids (gluconeogenesis)

Rapid-acting insulin

• humalog (Lispro)

• novolog (Aspart)

• apidra (Glulisine)

Onset: 15-30 min/Duration: about 5 hrs

Short-acting insulin

regular (Humulin R, Novolin R)

Onset: 15-30 min/Duration: 4-12 hrs

Intermediate-acting insulin

• isophane (NPH) Onset: 1-2 hrs/Duration: 14-24 hrs

• humulin N, Novolin N Onset: 15-30 min/Duration: 14-24 hrs

Long-acting insulin

• lantus (Glargine)

• levimir (Detemir)

Onset: 3-4 hrs/Duration: 20-24 hrs

Fixed combination insulin

• 70/30 NPH/regular ratio Onset: 30-60 min

• 50/50 NPH/regular ratio Onset: 30-60 min

• 75/25 NPH/lispro Onset: 5-15 min

• 70/30 NPH/aspart Onset: 5-15 min

Duration: 10-16 hrs

Insulin clinical uses:

Type 1 and 2 DM in children and adults, DOC for GDM, hyperkalemia (helps to push K+ into the cells and lowers K+)

Mixing insulin

Common practice in diabetic regimens, but not all insulins is compatible

• Long-acting insulin cannot be mixed with other insulins

• Clear insulin should be drawn into syringe first when mixing 2 types of insulin (clear to cloudy)

• Do not mix with U-500 insulin with other insulins due to the type of syringe used (TB)

Insulin adverse effects;

Hypoglycemia, weight gain, lipodystrophy

Insulin monitoring:

HgbA1c every 3-6 months, daily finger sticks

Biguanide

metformin (Glucophage)

metformin (Glucophage) mechanism of action:

• Increase peripheral glucose uptake and utilization

• Decrease hepatic glucose production

• Decrease intestinal absorption of glucose

metformin (Glucophage) clinical use:

First-line drug for type 2 DM in children and adults

metformin (Glucophage) precautions/contraindications:

Advanced renal disease, acute or chronic metabolic acidosis, advanced age → risk of lactic acidosis

• Safe to continue if eGFR > 60mL/min

• Assess benefits/risks if eGFR < 45mL/min

• Not recommended if eGFR between 30-45mL/min

• Contraindicated if eGFR < 30mL/min

Hold 48hrs before and 48hrs after radiological studies using contrast

metformin (Glucophage) adverse effects:

• GI disturbances (bloating, N/V/D), lactic acidosis

• Positive effects → weight loss, decreased lipids

metformin (Glucophage) monitoring:

Assess renal function before initiating and then annually; HgbA1c every 3-6 months, intermittent finger sticks

Sulfonylureas

• glipizide (Glucatrol)

• glyburide (Diabeta)

Sulfonylureas (glipizide, glyburide) mechanism of action:

Stimulate insulin release from pancreatic beta cells

Sulfonylureas (glipizide, glyburide) clinical use:

Second-line therapy for type 2 DM in adults

Sulfonylureas (glipizide, glyburide) precautions/contraindications:

• Pregnancy

• Lactation

• Type 1 DM (must have functioning beta cells)

• Hepatic/renal impairment

• Older adults (on BEERs list)

• Sulfa allergy

Sulfonylureas adverse effects:

Severe hypoglycemia, weight gain, GI upset, rash, photosensivity

Sulfonylureas (glipizide, glyburide) monitoring:

HgbA1c every 3-6 months, daily fingersticks

Sulfonylureas patient education:

• Hold if unable to eat

• Interacts with alcohol → severe hypoglycemia

Thiazolidinediones (TZD)

• pioglitazone (Actos)

• rosiglitazone (Avandia)

Thiazolidinediones (TZD) (pioglitazone, rosiglitazone) mechanism of action:

Improve target-cell response to insulin; depend on presence of insulin

Thiazolidinediones (TZD) (pioglitazone, rosiglitazone) clinical use:

Type 2 DM in adults

Thiazolidinediones (TZD) precautions/contraindications:

Class III and IV heart failure

Thiazolidinediones (TZD) (pioglitazone, rosiglitazone) adverse effects:

Weight gain, edema

Alpha-glucosidase Inhibitors

• acarbose (Precose)

• miglitol (Glyset)

Alpha-glucosidase Inhibitors (acarbose, miglitol) mechanism of action:

Delay digestion and absorption of carbohydrates in the small intestine

Alpha-glucosidase Inhibitors clinical use:

Type 2 DM in adults

Alpha-glucosidase Inhibitors (acarbose, miglitol) precautions/contraindications:

Bowel disease, severe renal impairment

Alpha-glucosidase Inhibitors (acarbose, miglitol) adverse effects:

GI upset (gas, bloating)

Alpha-glucosidase Inhibitors patient education:

Take with first bite of a meal → low incidence of hypoglycemia

Meglitinides

• repaglinide (Prandin)

• nateglinide (Starlix)

Meglitinides mechanism of action:

Block ATP potassium channels on beta islet cells which opens calcium channels → influx of calcium increases secretion of insulin

Meglitinides (repaglinide, nateglinide) clinical use:

Type 2 DM in adults

Meglitinides (nateglinide, repaglinide) precautions/contraindications:

Hepatic/renal impairment

Meglitinides adverse effects:

Hypoglycemia

Meglitinides (repaglinide, nateglinide) patient education:

Take 30 minutes before meal, hold if unable to eat

Selective Sodium Glucose Cotransporter 2 (SGLT-2) Inhibitors

• dapagliflozin (Farxiga)

• empagliflozin (Jardiance)

SGLT-2 mechanism of action:

Block reabsorption of glucose in kidneys and promote excretion of excess glucose in the urine

SGLT-2 clinical use:

Type 2 DM in adults, recommended for patients with HF

SGLT-2 precautions/contraindications:

Severe renal impairment

SGLT-2 adverse effects:

Genital fungal infections, UTI, increased urination, volume depletion

SGLT-2 monitoring:

Urine dip will be + for glucose

SGLT-2 patient education:

Report s/sxs of dehydration, yeast infection

Dipeptidyl peptidase-4 (DPP-4) Inhibitors

• sitagliptin (Januvia)

• saxagliptin (Onglyza)

DPP-4 Inhibitors (sitagliptin, saxagliptin) mechanism of action:

Increase and prolong incretin hormone (GLP-1) activity which increases insulin synthesis and release from pancreatic beta cells

DPP-4 Inhibitors clinical use:

Type 2 DM in adults

DPP-4 Inhibitors (slitagliptin, saxagliptin) precautions/contraindications:

Renal impairment and heart failure

DPP-4 Inhibitors (sitagliptin, saxagliptin) adverse effects:

• Hypoglycemia, arthralgias, UTIs, URIs

• Positive effect → weight loss

DPP-4 Inhibitors (sitagliptin, saxagliptin) monitoring:

Renal function before initiating and then annually

Glucagon-like Peptide- (GLP-1) Agonists

• liraglutide (Victoza)

• semaglutide (Ozempic, Wegovy, Rybelsus)

GLP-1 Agonists (liraglutide, semaglutide) mechanism of action:

Stimulate insulin secretion from pancreatic beta cells, decrease glucagon release from alpha cells, slow gastric emptying

GLP-1 Agonists clinical use:

Type 2 DM in adults, recommended for patients with CVD; weight management (Wegovy)

GLP-1 Agonists (liraglutide, semaglutide) precautions/contraindications:

Severe GI disease, family hx of thyroid cancer, renal impairment

GLP-1 Agonists adverse effects:

GI upset (N/V), thyroid tumors

GLP-1 Agonists (liraglutide, semaglutide) patient education:

Do not mix with insulin, rotate injection sites