Pharmacotherapy for Diabetes Mellitus

The goal of insulin therapy is to ___ natural blood glucose regulation. Nurses should ensure ____ is available when glucose is present in the blood

Mimic, insulin

____ insulin maintains glucose during fasting

Basal

____ insulin is released after meals

Prandial

Insulin dosing should be ____ to control blood sugar, monitor peak times to prevent _____

Individualized, hypoglycemia

You should consider insulin in ____ ____ DM, ____ ____ DM, and ____ patients.

Type 1, Type 2, pregnant

Nurses should consider insulin when Hemoglobin A1c is >____%, fasting glucose > ____ mg/dL, after exhausting oral medications and if patient has symptoms of _____

10, 300, hyperglycemia

Conventional Insulins (synthetic human insulins): _____ is rapid-acting, short duration (only one that can be administered IV)

Regular

Conventional Insulins (synthetic human insulins): _____ and ____ are intermediate-acting and have a longer duration

NPH, Lente

Conventional Insulins (synthetic human insulins): _____ is long-acting + has long duration

Ultralente

Analogue Insulins (modified insulins for faster or longer action): ____ and ___ are RAPID acting

Lispro (Humalog), Aspart (NovoLog)

Analogue Insulins (modified insulins for faster or longer action): ____ and ___ are LONG acting

Detemir (Levemir), Glargine (Lantus, Basaglar)

Analogue Insulins (modified insulins for faster or longer action): ____ is ULTRA LONG acting

Degludec (Tresiba)

There are 3 main insulin types: ____ acting, _____ acting, and ____ acting

Short, intermediate, long

Insulins can be _____ to mimic fasting (basal) & meal (prandial) insulin

Combined

Nurses should ____ rapid/short-acting insulins if blood glucose < 70 mg/dL

Hold

The primary adverse effect of insulin therapy is ______. Other reactions include ____ phenomenon, swollen lymph glands, urticaria, and injection-site reactions

Hypoglycemia (augmented reaction), Somogyi

The treatment goals of people with GDM is to replace normal physiological insulin amounts. The target Hgb A1c < ___%.

6

The treatment goals of people with T1DM is to replace normal physiological insulin amounts. The Target Hgb A1c < ____%

6.5

The treatment goals of people with T2DM is insulin that may be used alone or with antidiabetic agent. The target Hgb A1c < ____% and may vary based on patient characteristics

7

Adjunct Insulin Therapy includes ______ (Symlin) is a synthetic amylin analog + works with insulin to control glucose. It should be administer at ____ sites from insulin (can't be mixed with insulin)

Pramlintide, different

The common treatment for optimal glycemic control is ____ _____ insulin which is a once-daily long-acting insulin for fasting glucose control and ____ ____ which boluses of rapid-acting insulin for post-meal glucose control. *Some patients may need twice-daily basal insulin dosing

Basal insulin, prandial insulin

___ ____ insulin includes examples such as Lispro (Humalog) and Aspart (NovoLog). The onset is 10–15 min. The peak is 1–2 hrs and the duration is 3–5 hrs. This type of insulin is primarily used for post-meal glucose control; can be given IV in critical care

Rapid acting

___ ____ insulin includes examples such as regular insulin. The onset is 30–60 min. The peak is 2–4 hrs and the duration is 5–8 hrs. It is used for post-meal glucose; only insulin safe for IV use

Short acting

____ ____ insulin includes examples such as NPH (Humulin N). The onset is 1–2 hrs. The peak is 4–12 hrs and the duration is 12–18 hrs. It is used for basal coverage; often twice daily

Intermediate acting

____ ____ insulin includes examples such as Glargine (Lantus) and Detemir (Levemir). The onset is around ~1–2 hrs. There is NO peak and the duration is ~24 hrs. It is used for basal control and to have a steady insulin level

Long acting

Peak is where ____ risk highest!

Hypogylcemia

PROTOTYPE: ____ ____ ___ is an antidiabetic + pancreatic hormone, short-acting hypoglycemic

MOA: increases glucose uptake, stimulates glycogen storage and inhibits glucagon release

ADR: lipodystrophy, weight gain, hypoglycemia

Overdose Treatment: IV D50, glucagon, oral glucose

Similar Drugs: Humulin R and Novolin R

Nursing Considerations: should be stored at room temperature, rotate injection sites, monitor blood glucose, recognize hypoglycemia, ensure patient carries glucose supply, carry glucose, monitors for signs of lipodystrophy, wears medical alert

Human regular insulin

____ ___ are introduced when lifestyle changes are insufficient. ____ Treatment follows a stepwise approach, starting with lifestyle modifications to improve glycemic control. If monotherapy with oral agents fails to control glucose, ____ therapy often provides better results

Antidiabetic agents, T2DM, combination

The ____ ____ used anti-diabetic drug classes are Biguanides, Incretin Mimetics such as GLP-1 Receptor Agonists and Dual GLP-1/GIP Agonists, and SGLT2 Inhibitors

Most frequently

The ____ ____ anti-diabetic drug classes are Sulfonylureas, Thiazolidinediones (TZD), and DPP-4 Inhibitors

Moderate use

The ____ ____ used anti-diabetic drug classes are Alpha-Glucosidase Inhibitors, Amylin Mimetics, and Meglitinides

Less frequently

The anti-diabetic drug class is based on the ____ + ____ risk + weight effect + CV/renal benefit

Mechanism, hypoglycemia

_____ increases insulin sensitivity and DECREASE liver glucose production. They decrease triglycerides, LDL, total cholesterol, body weight and increase HDL. Dosing should be once or twice daily. Benefits include DECREASED CV events & mortality. The risk is a very low risk hypoglycemia, may cause B12 deficiency, caution with lactic acidosis

Biguanides (Example: Metformin Glucophage

PROTOTYPE: ____ is an anti-diabetic and a biguanide

MOA: Decreases glucose by inhibiting gluconeogenesis, hepatic glucose production, and intestinal reabsorption; ↑ glucose uptake & ↑ insulin sensitivity

ADR: Anorexia, N/V, severe diarrhea, weight loss, abdominal pain, metallic taste, dizziness, fatigue

Black Box: Lactic acidosis (rare, fatal)

Contraindications: IV contrast (stop 2 days before/after), HF, CKD, hyperthyroid

Nursing Considerations: Give with meals, monitor GI symptoms, monitor renal function, educate to take with meals, monitor for lactic acidosis, and stop 2 days before/after IV contrast

Metformin

____ ____ ____ activates glucagon-like peptide-1 (GLP-1) receptors to increase insulin secretion (glucose-dependent), ↓ glucagon, ↓ gastric emptying, ↑ satiety. The dosing is subcutaneous, some oral (semaglutide). They DECREASE A1C, weight, postprandial glucose. They benefit by decreasing blood glucose, gastric emptying and increasing satiety thus decreasing weight, inflammation & atherosclerosis which ↓ ASCVD (MI, stroke, CV death), ↓ albuminuria & ↓ CKD progression and ↓ liver fat (MASH) and possible ↓ cognitive decline/addictive behaviors → which decreases mortality and LOW hypoglycemia risk when used alone. ADRs include N/V/D, pancreatitis, GB disease; avoid in medullary thyroid cancer/MEN2

GLP-1 Receptor Agonists (Examples are Exenatide, Semaglutide, Liraglutide, Dulaglutide)

PROTOTYPE: _____ is a GLP-1 Receptor Agonist

MOA: Mimics endogenous GLP-1 leading ↑ glucosedependent insulin secretion, ↓ glucagon, slows gastric emptying, ↑ satiety → lowers blood glucose in T2DM

ADRs: Nausea (most common), vomiting, diarrhea, headache; hypoglycemia (with insulin/sulfonylureas); pancreatitis

Contraindications: Personal/family history of medullary thyroid carcinoma (MTC), MEN 2. Use caution with history of pancreatitis or severe GI disease (gastroparesis)

Nursing Considerations: Administer exenatide SQ before meals (usually BID), monitor blood glucose and signs of pancreatitis (severe abdominal pain), monitor renal function (risk with dehydration from GI effects), take before meals; expect nausea initially; report severe abdominal pain; recognize hypoglycemia if used with insulin/sulfonylureas

Exenatide

Dual Incretin: ___ ____ activates GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors which INCREASES insulin (glucose-dependent), ↓ glucagon, ↓ gastric emptying, ↑ satiety. Dosing is subcutaneous and once weekly. Effects include ↓ A1C, greater ↓ weight, ↓ postprandial glucose. Benefits are the same as GLP-1 RA + enhanced weight loss effect. Major ADRs include N/V/D, pancreatitis, gallbladder disease ▪ Avoid in medullary thyroid cancer/MEN2

GLP-1/GIP Agonist (Example: Tirzepatide)

____ ____ blocks sodium-glucose co-transporter 2 (SGLT2) in renal tubules leads to an increase in urinary glucose excretion. Effects include ↓ A1C, weight, systolic BP; ↑ urinary glucose. Dosing should be oral, once daily (before first meal of the day). Benefits include a ↓ CV events, HF hospitalization, CKD progression; weight loss; low hypoglycemia risk. These are the first-line for those with CVD & CKD. Risks include genital infections, UTIs, volume depletion, hypotension, ↑ risk of amputation (canagliflozin)

SGLT2 Inhibitors (Example: Canagliflozin (Invokana), Empagliflozin (Jardiance), Dapagliflozin (Farxiga)

PROTOTYPE: _____ is a SGLT2 Inhibitor

MOA: Inhibits SGLT2 in the kidneys, reducing glucose reabsorption, increasing glucose excretion in urine, and lowering blood glucose levels

ADRs: Dehydration, hypotension, UTI, genital infections, hyperkalemia, DKA (if used with insulin/sulfonylurea)

Contraindications: T1DM, DKA, CKD (eGFR <30), ESRD, pregnancy, lactation

Nursing Considerations: Monitor blood glucose, renal function (eGFR), electrolytes (K+), hydration status, asses for signs of UTI, genital infections, dehydration, and DKA, teach patients hydration is key; watch for symptoms of dehydration or infection, regular renal function testing is necessary

Canagliflozin

_____ stimulate pancreatic beta cells to secrete insulin, ↑ insulin receptor sensitivity. These cause A1c ↓: 0.6-1.2%. The type includes insulin secretagogues (1st & 2nd gen; 2nd gen more potent). Risk includes caution with hypoglycemia and dosing should be 30 minutes before meal

Sulfonylureas (Example Glyburide (Diabeta), Glipizide (Glucotrol)

PROTOTYPE: _____ is a sulfonylurea

MOA: Stimulates insulin secretion from pancreatic beta cells independent of glucose level, increasing circulating insulin and lowering blood glucose in T2DM

ADRs: Hypoglycemia (priority), weight gain, nausea, rash, dizziness; rare hematologic effects (leukopenia, thrombocytopenia)

Contraindications: Hypersensitivity, T1DM, DKA, severe renal impairment (↑ prolonged hypoglycemia risk), severe hepatic impairment

Nursing Considerations: Give 30 min before breakfast; ensure meal follows, hold if NPO or poor intake, monitor blood glucose & hypoglycemia (priority), use caution in older adults and renal impairment (avoid if possible), monitor for weight gain, take before meals and do not skip eating; recognize/treat hypoglycemia (carry fast glucose); avoid alcohol

Glyburide

________ increase insulin sensitivity in muscle/adipose tissue and ↓ hepatic glucose production. Effects include ↑ HDL, may ↑ LDL and weight; minimal effect on triglycerides. Dosing includes once daily with or without food. Benefits include that they improve insulin resistance; potential CV benefit with pioglitazone. Risks are fluid retention, HF exacerbation, fractures, hepatotoxicity, very low hypoglycemia risk

Thiazolidnediones (TZD) (Example: Pioglitazone (Actos), Rosiglitazone (Avandia)

PROTOTYPE: _____ is a thiazolidinedione

MOA: Improves insulin sensitivity in muscle and adipose tissue via PPAR-γ activation → ↑ glucose uptake, ↓ hepatic glucose production

ADR: Weight gain, edema (fluid retention), anemia, headache, fatigue, ↑ LDL/HDL; ↑ fracture risk (especially women)

Black Box: Causes or worsens heart failure due to fluid retention (not for NYHA III–IV HF; monitor for dyspnea, edema, rapid weight gain)

Contraindications: Heart failure, active liver disease, T1DM, DKA

Interactions: CYP2C8 inhibitors (gemfibrozil) increases levels CYP2C8 inducers (rifampin) which DECREASES effectiveness

Nursing Considerations: Monitor for heart failure, monitor liver function tests, monitor weight and lipids, avoid in HF, use caution in hepatic impairment, patients should report swelling/SOB or rapid weight gain; expect delayed effect (weeks); reinforce diet/exercise

Rosiglitazone

____ ____ inhibit dipeptidyl peptidase-4 (DPP-4) enzyme which increases endogenous GLP-1 & GIP leading to ↑ insulin secretion and ↓ glucagon. These ↓ A1C (modest), especially postprandial glucose; weight-neutral. Dosing is oral and once daily (dose adjust in renal impairment except linagliptin). Benefits include that they are well-tolerated, low risk of hypoglycemia, weight neutral. Risks include headache, nasopharyngitis, pancreatitis (rare), joint pain

DPP-4 Inhibitors (Gliptins) (Examples: Sitagliptin (Januvia), Linagliptin (Tradjenta), Saxagliptin (Onglyza), Alogliptin (Nesina)

PROTOTYPE: _____ is a DPP-4 Inhibitor

MOA: Inhibits DPP-4 enzyme, which breaks down incretin hormones. This inhibition increases incretin levels, leading to enhanced insulin secretion and reduced glucagon release in response to meals, lowering blood glucose levels in T2DM

ADRs: Upper respiratory infections, headache, nasopharyngitis, hypoglycemia (with insulin/sulfonylurea), pancreatitis (rare)

Contraindications: Hypersensitivity to sitagliptin, history of pancreatitis, renal impairment (dose adjustment needed)

Nursing Considerations: Administer oral and once daily with or without food, monitor renal function (eGFR), blood glucose levels, advice patients to report symptoms of pancreatitis, monitor for hypoglycemia when used with insulin or sulfonylureas

Sitagliptin

DM Meds: Insulin and sulfonylureas a higher risk/effect and metformin, GLP-1 receptor agonists, SGLT2 inhibitors, DPP-4 inhibitors have a lower risk and are favorable for _____

Hypoglycemia

DM Meds: GLP-1 receptor agonists and GLT2 inhibitors have a lower risk/favorable for ___ ___

Weight loss

DM Meds: Insulin, Sulfonylureas, Thiazolidinediones (TZDs) have a higher risk/effect for ___ ___

Weight gain

DM Meds: GLP-1 receptor agonists have a higher risk/effect for ____ ____

ASCVD benefit

DM Meds: SGLT2 inhibitors have a lower risk and are favorable for ___ ____

Heart Failure (CKD Benefit)

_____ stimulate rapid insulin release from pancreatic beta cells leading to ↑ insulin and ↓ postprandial glucose. Dosing should be oral and before meals (up to 3x/day). Effects include ↓ postprandial glucose. Benefits include that there is flexible dosing with meals. Risks include ↑ hypoglycemia (less than sulfonylureas), increased weight. ADRs: Hypoglycemia, N/V/D

Meglitinides (Rapid Secretagogues) (Example = Repaglinide)

_____ _____ _____ inhibit intestinal enzymes leading to ↓ carbohydrate breakdown which ↓ glucose absorption and ↓ postprandial glucose. Dosing is oral, with first bite of meal. Effects include ↓ postprandial glucose (modest). Benefits include no weight gain, low hypoglycemia risk. Risks are GI intolerance limits use. ADRs include flatulence, diarrhea, abdominal pain

Alpha Glucosidase Inhibitors (GI Acting)(Example = Acarbose)

____ ____ mimics amylin leading to ↓ gastric emptying + ↓ glucagon + ↑ satiety which ↓ postprandial glucose. Dosing is subcutaneous before meals. Effects include ↓ postprandial glucose. Benefits include that they help control post-meal spikes. Risks include that they ↑ hypoglycemia when combined with insulin. ADRs are nausea, anorexia, hypoglycemia

Amylin Mimetic (Adjunct to Insulin) (Example = Pramlintide)

____ Treatment Goals/Stepwise Management: Targets (non-pregnant adults) A1C <7% (individualize), Fasting 80–130 mg/dL, Postprandial <180 mg/dL, avoid hypoglycemia <70 mg/dL

T2DM

T2DM Treatment Approach: Start ____ + ____ (if no contraindication), if not at target in ~3 months you should add second agent, consider early combination if A1C ≥ 9% and insulin if A1C ≥10%, glucose ≥300, or symptomatic

Lifestyle, metformin

T2DM Drug Selection: Some require ____ function (sulfonylureas); others do not (metformin, SGLT2, insulin), NOT effective in T1DM (except insulin); many can be combined with ____, ASCVD/high risk (GLP-1 RA or SGLT2 inhibitor) and HF or CKD → (SGLT2 inhibitor)

Pancreatic, insulin