Diabetes Meds Cheat Sheet: FNP Pharmacology Breakdown

Pharmacology · 12 min read · July 15, 2026

Diabetes Medications Cheat Sheet: The Complete FNP Pharmacology Breakdown

Diabetes pharmacology is one of the most important—and most frequently misunderstood—areas of FNP board preparation. It is no longer enough to memorize that “metformin is first-line” or that “sulfonylureas cause hypoglycemia.” Modern diabetes treatment is individualized according to the patient’s cardiovascular risk, kidney function, heart-failure status, weight goals, risk of hypoglycemia, medication cost, and personal preferences.

For the AANP and ANCC exams, you should be able to answer five questions about every major diabetes medication:

How does it work?
How much does it lower glucose?
Does it cause hypoglycemia?
Does it cause weight gain or weight loss?
When should it be avoided—or specifically selected?

This guide breaks down the major medication classes, their mechanisms, adverse effects, contraindications, and the clinical clues that frequently appear in board-style questions.

The most important principle: There is no single “best” diabetes medication for every patient. The best choice is the medication that addresses the individual patient’s glycemic needs, comorbidities, risks, preferences, and access.

The Big Picture: Choosing a Diabetes Medication

Before choosing a medication, assess the whole patient—not merely the A1C.

Important factors include:

Current A1C and individualized A1C goal
Symptoms of hyperglycemia
Evidence of insulin deficiency or catabolism
Established atherosclerotic cardiovascular disease
Heart failure
Chronic kidney disease
Body weight and weight-management goals
Risk of hypoglycemia
Kidney and liver function
Medication cost and insurance coverage
Pregnancy or plans for pregnancy
Ability to administer injectable therapy
Patient preferences and treatment burden

When should insulin be considered early?

Insulin should be considered when a patient has:

Severe symptomatic hyperglycemia
Polyuria, polydipsia, dehydration, or blurred vision
Unintentional weight loss or other evidence of catabolism
Ketosis or suspected insulin deficiency
A very high A1C or blood glucose level
Type 1 diabetes
Diabetic ketoacidosis or hyperosmolar hyperglycemic state
Acute illness in which non-insulin medications are unsafe or insufficient

A common board-exam clue is a patient with an A1C above approximately 10%, blood glucose at or above approximately 300 mg/dL, significant symptoms, or weight loss. These findings should make you consider insulin rather than simply adding another oral medication.

Diabetes Medication Comparison at a Glance

Medication class	Hypoglycemia alone	Weight effect	Major clinical advantage	Major concern
Metformin	Low	Neutral or modest loss	Effective, inexpensive, familiar	GI effects; renal restrictions
Sulfonylureas	High	Gain	Inexpensive and effective	Hypoglycemia
Meglitinides	Moderate	Gain	Targets postprandial glucose	Frequent dosing; hypoglycemia
Thiazolidinediones	Low	Gain	Improves insulin sensitivity	Edema and heart failure
DPP-4 inhibitors	Low	Neutral	Well tolerated and oral	Modest efficacy
GLP-1 receptor agonists	Low	Loss	Strong glucose and weight effects	GI effects; class warnings
Dual GIP/GLP-1 agonist	Low	Significant loss	Very strong glucose and weight effects	GI effects; class warnings
SGLT2 inhibitors	Low	Modest loss	Heart and kidney benefits	Genital infections; ketoacidosis
Alpha-glucosidase inhibitors	Low	Neutral	Reduces post-meal glucose	GI effects
Insulin	High	Gain	Greatest glucose-lowering ability	Hypoglycemia

Hypoglycemia risk increases when agents that ordinarily have a low risk are combined with insulin, sulfonylureas, or meglitinides.

1. Metformin: The Biguanide

Metformin remains a foundational medication for many patients with type 2 diabetes because it is effective, inexpensive, familiar, generally weight-neutral, and unlikely to cause hypoglycemia when used alone.

However, metformin is no longer automatically the only appropriate initial medication for every patient. A person with significant cardiovascular disease, heart failure, chronic kidney disease, or a major weight-management goal may need an SGLT2 inhibitor, a GLP-1 receptor agonist, or another individualized treatment—with or without metformin.

Mechanism of action

Metformin primarily:

Decreases hepatic glucose production
Improves peripheral insulin sensitivity
Modestly decreases intestinal glucose absorption

The easiest way to remember it is:

Metformin tells the liver to make less glucose and helps the body respond better to insulin.

Advantages

Low risk of hypoglycemia when used alone
Weight-neutral or associated with modest weight loss
Inexpensive
Available in immediate-release and extended-release formulations
Extensive clinical experience

Common adverse effects

Gastrointestinal symptoms are the most common:

Diarrhea
Nausea
Abdominal discomfort
Bloating
Decreased appetite
Metallic taste

These effects can often be reduced by:

Starting at a low dose
Titrating gradually
Taking the medication with food
Switching to an extended-release formulation

Vitamin B12 deficiency

Long-term metformin use can reduce vitamin B12 absorption. Consider periodic B12 assessment, particularly when a patient develops:

Anemia
Peripheral neuropathy
Paresthesias
Cognitive changes
Long-term or high-dose exposure
Other risk factors for B12 deficiency

Do not automatically assume that neuropathy in a patient with diabetes is caused by diabetes. Medication-associated B12 deficiency is an important alternative diagnosis.

Lactic acidosis

Metformin-associated lactic acidosis is rare but serious. Risk increases when metformin accumulates or when another condition causes significant tissue hypoxia or impaired lactate clearance.

Concerning situations include:

Severe kidney dysfunction
Sepsis
Shock
Acute hypoxemia
Acute decompensated heart failure
Severe liver dysfunction
Excessive alcohol intake
Dehydration or severe acute illness

Stable heart failure is not an automatic contraindication, but metformin may need to be temporarily held during acute decompensation, hypoperfusion, hypoxemia, or another serious illness.

Kidney-function rules

eGFR below 30 mL/min/1.73 m²

Metformin is contraindicated.

eGFR 30–44 mL/min/1.73 m²

Do not generally initiate metformin in a new patient within this range. For a patient already taking it, reassess the benefits and risks, consider dose reduction, and monitor kidney function more closely.

eGFR 45 mL/min/1.73 m² or higher

Metformin can generally be used when otherwise appropriate, with routine renal monitoring.

Iodinated contrast

Metformin does not directly interact with contrast dye. The concern is that contrast-associated acute kidney injury could lead to metformin accumulation.

Depending on eGFR, route of contrast administration, liver disease, heart failure, alcoholism, and the specific procedure, metformin may need to be held at or before contrast administration and restarted after renal function is confirmed to be stable.

Follow the product labeling and the imaging facility’s protocol rather than applying one rule to every patient.

Board pearl: Metformin alone does not usually cause hypoglycemia. The renal threshold to know is an eGFR below 30 mL/min/1.73 m².

2. Sulfonylureas

Common sulfonylureas include:

Glipizide
Glimepiride
Glyburide

These medications are inexpensive and effective, but their use is limited by hypoglycemia and weight gain.

Mechanism of action

Sulfonylureas stimulate pancreatic beta cells to release insulin by closing ATP-sensitive potassium channels.

Their effect is not tightly dependent on the current blood glucose level. That is why they can continue increasing insulin secretion even when glucose is already low.

Memory aid: Sulfonylureas squeeze insulin out of the pancreas.

Advantages

Oral administration
Relatively rapid glucose-lowering effect
Inexpensive
Widely available

Major adverse effects

Hypoglycemia
Weight gain
Declining effectiveness as beta-cell function deteriorates

Hypoglycemia risk is greater in:

Older adults
Patients with kidney or liver impairment
Patients who skip meals
Patients with inconsistent food intake
Patients taking multiple glucose-lowering medications
Patients with impaired awareness of hypoglycemia

Which sulfonylurea is generally preferred?

Glipizide is often preferred when a sulfonylurea must be used in a patient with chronic kidney disease because it has less risk of prolonged hypoglycemia than glyburide.

Glyburide should generally be avoided in older adults and patients with impaired kidney function because active metabolites can accumulate and cause prolonged hypoglycemia.

Patient education

Teach patients to:

Eat meals consistently
Recognize sweating, shakiness, hunger, confusion, palpitations, and dizziness as possible hypoglycemia
Carry a rapid source of glucose
Monitor glucose as directed
Avoid doubling a missed dose
Understand that alcohol may increase hypoglycemia risk

Board pearl: If an older patient with kidney disease has recurrent or prolonged hypoglycemia while taking glyburide, the medication is a likely cause.

3. Meglitinides

Examples include:

Repaglinide
Nateglinide

Meglitinides stimulate insulin secretion but have a faster onset and shorter duration of action than sulfonylureas.

Mechanism of action

These drugs stimulate pancreatic insulin release around mealtimes, primarily targeting postprandial glucose elevations.

Administration rule

They are taken shortly before meals.

No meal, no dose.

If the patient skips a meal, the corresponding dose should generally be skipped.

Advantages

Flexible mealtime dosing
Useful for postprandial hyperglycemia
Shorter duration than sulfonylureas

Adverse effects

Hypoglycemia
Weight gain
Frequent dosing burden

Repaglinide has an important interaction with gemfibrozil that can substantially increase repaglinide exposure and hypoglycemia risk; the combination should be avoided.

Board pearl: A medication taken before meals and skipped when the meal is skipped is most likely a meglitinide.

4. Thiazolidinediones

Common thiazolidinediones, or TZDs, include:

Pioglitazone
Rosiglitazone

Mechanism of action

TZDs activate the peroxisome proliferator-activated receptor gamma, or PPAR-γ, which improves insulin sensitivity in adipose tissue, skeletal muscle, and the liver.

They do not force the pancreas to secrete insulin, so they have a low risk of hypoglycemia when used alone.

Clinical characteristics

Oral medications
Low hypoglycemia risk alone
Delayed onset of maximal effect
Can cause weight gain
Can cause fluid retention

Major adverse effects

Edema
Weight gain
New or worsening heart failure
Increased fracture risk
Possible macular edema
Ovulation and unintended pregnancy in some anovulatory premenopausal patients

Heart-failure warning

TZDs can cause dose-related fluid retention and exacerbate heart failure. They should not be initiated in patients with New York Heart Association class III or IV heart failure and should be used very cautiously—or avoided—in patients with symptomatic heart failure.

This class does not merely cause “weight gain.” Rapid weight gain accompanied by edema or dyspnea may represent fluid retention and worsening heart failure.

Pioglitazone and bladder cancer

Avoid pioglitazone in patients with active bladder cancer. In patients with a history of bladder cancer or unexplained hematuria, carefully weigh potential benefits and risks.

Board pearl: Diabetes plus heart failure plus lower-extremity edema is a strong reason to avoid a thiazolidinedione.

5. DPP-4 Inhibitors

Common dipeptidyl peptidase-4 inhibitors include:

Sitagliptin
Linagliptin
Saxagliptin
Alogliptin

Mechanism of action

DPP-4 inhibitors prevent the breakdown of endogenous incretin hormones. This results in:

Increased glucose-dependent insulin secretion
Decreased glucagon secretion

Because the effect is glucose-dependent, these medications have a low risk of hypoglycemia when used alone.

Advantages

Oral administration
Weight-neutral
Low hypoglycemia risk
Generally well tolerated

Limitations

Modest A1C reduction
Less weight benefit than GLP-1–based medications
No reason to combine with a GLP-1 receptor agonist
Cost may be significant

Kidney considerations

Most DPP-4 inhibitors require renal dose adjustment.

Linagliptin is the major exception and generally does not require dose adjustment for kidney impairment.

Important adverse effects and warnings

Severe joint pain
Hypersensitivity reactions
Possible pancreatitis
Bullous pemphigoid
Heart-failure concern with saxagliptin and alogliptin

Saxagliptin and alogliptin should be used cautiously in patients with heart failure or at high risk for heart failure.

Board pearl: Linagliptin is the DPP-4 inhibitor most associated with “no renal dose adjustment.”

6. GLP-1 Receptor Agonists

Common GLP-1 receptor agonists include:

Semaglutide
Dulaglutide
Liraglutide
Exenatide
Lixisenatide

Most are injectable, although oral semaglutide is available.

Mechanism of action

GLP-1 receptor agonists:

Increase glucose-dependent insulin secretion
Decrease glucagon secretion
Slow gastric emptying
Increase satiety
Reduce food intake

Because insulin secretion is glucose-dependent, hypoglycemia risk is low when these medications are used alone. Risk rises when combined with insulin or an insulin secretagogue.

Major benefits

Depending on the specific agent, benefits may include:

Strong A1C reduction
Clinically meaningful weight loss
Cardiovascular risk reduction
Low hypoglycemia risk when used without insulin or a secretagogue
Possible kidney benefits

Cardiovascular outcome evidence is drug-specific. Do not assume every medication in the class has identical outcome data.

Common adverse effects

Nausea
Vomiting
Diarrhea
Constipation
Abdominal discomfort
Reduced appetite

GI effects are often most pronounced when starting therapy or increasing the dose. Slow dose escalation may improve tolerability.

Important warnings and precautions

Thyroid C-cell tumor warning

Certain long-acting GLP-1–based therapies carry a boxed warning related to thyroid C-cell tumors observed in rodents.

They are contraindicated in patients with:

A personal history of medullary thyroid carcinoma
A family history of medullary thyroid carcinoma
Multiple endocrine neoplasia syndrome type 2

This warning does not mean that every thyroid disorder is a contraindication. Hashimoto thyroiditis, routine hypothyroidism, benign thyroid nodules, and a history of nonmedullary thyroid cancer are not automatically equivalent to MTC or MEN2. Each patient still requires an individualized assessment.

Pancreatitis

Stop the medication and evaluate promptly if pancreatitis is suspected. Persistent, severe abdominal pain—particularly when radiating to the back and accompanied by vomiting—is concerning.

A prior history of pancreatitis warrants careful consideration, but the exact precautions should be based on the medication’s labeling and the patient’s circumstances.

Gallbladder disease

These agents can be associated with:

Cholelithiasis
Cholecystitis
Biliary symptoms

Gastroparesis

Because GLP-1 receptor agonists slow gastric emptying, they are generally poor choices for patients with severe gastroparesis or other significant gastric-emptying disorders.

Diabetic retinopathy

Rapid improvement in glycemia may temporarily worsen diabetic retinopathy in susceptible patients. Patients with existing retinopathy may need closer ophthalmologic monitoring when therapy is intensified.

Important combination rule

Do not routinely combine a GLP-1 receptor agonist with a DPP-4 inhibitor. Both act through the incretin pathway, and combining them generally adds cost and treatment burden without meaningful additional benefit.

Board pearl: GLP-1 receptor agonists lower glucose, promote weight loss, and have a low hypoglycemia risk alone. Think GI effects, MTC/MEN2 contraindication, pancreatitis warning, gallbladder disease, and delayed gastric emptying.

7. Tirzepatide: Dual GIP and GLP-1 Receptor Agonist

Tirzepatide is not simply another traditional GLP-1 receptor agonist. It is a dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist.

Mechanism and effects

Tirzepatide:

Enhances glucose-dependent insulin secretion
Reduces glucagon
Slows gastric emptying
Increases satiety
Produces substantial A1C reduction
Produces significant weight loss in many patients

Adverse effects and precautions

Its major safety considerations overlap with GLP-1 receptor agonists:

Nausea
Vomiting
Diarrhea
Constipation
Abdominal discomfort
Pancreatitis warning
Gallbladder disease
Delayed gastric emptying
MTC/MEN2 contraindication

Oral contraceptive consideration

Because tirzepatide can delay gastric emptying and potentially affect oral medication absorption, its prescribing information includes special guidance for patients using oral hormonal contraceptives during initiation and dose escalation. Review the current labeling and counsel patients about an appropriate alternative or backup method during the specified periods.

Board pearl: Tirzepatide activates both GIP and GLP-1 receptors. It is associated with powerful glucose lowering and weight loss but shares many of the GI and endocrine warnings of GLP-1–based therapy.

8. SGLT2 Inhibitors

Common sodium-glucose cotransporter-2 inhibitors include:

Empagliflozin
Dapagliflozin
Canagliflozin
Ertugliflozin

Mechanism of action

SGLT2 inhibitors block glucose and sodium reabsorption in the proximal renal tubule. This causes:

Glucose to be excreted in the urine
Mild osmotic diuresis
Modest weight loss
A modest reduction in blood pressure

Memory aid: SGLT2 inhibitors send glucose out through the urine.

Major benefits

Depending on the specific medication and indication, this class can:

Reduce heart-failure hospitalization
Slow progression of chronic kidney disease
Reduce cardiovascular events in selected patients
Provide benefits that extend beyond A1C reduction

Some SGLT2 inhibitors are used for heart failure or chronic kidney disease even in people without diabetes.

Common adverse effects

Genital mycotic infections
Increased urination
Volume depletion
Dizziness or hypotension
Dehydration
Urinary symptoms

Genital fungal infections are more characteristic than routine bacterial urinary tract infections.

Euglycemic diabetic ketoacidosis

SGLT2 inhibitors can cause diabetic ketoacidosis even when the glucose is not dramatically elevated.

Risk increases with:

Acute illness
Surgery
Prolonged fasting
Severe carbohydrate restriction
Dehydration
Insulin dose reduction or omission
Heavy alcohol use
States of relative insulin deficiency

Symptoms may include:

Nausea
Vomiting
Abdominal pain
Malaise
Dyspnea
Confusion

A near-normal glucose level does not exclude DKA in a patient taking an SGLT2 inhibitor.

Surgery and fasting

SGLT2 inhibitors should be withheld before scheduled surgery to reduce the risk of perioperative ketoacidosis. The timing varies by medication:

Most should be stopped at least three days before surgery.
Ertugliflozin should generally be stopped at least four days before surgery.

The FDA specifically warns about this perioperative risk. FDA Drug Safety Communication

Fournier gangrene

A rare but serious necrotizing infection of the perineum has been reported. Severe genital or perineal pain, swelling, erythema, fever, or systemic illness requires urgent evaluation.

Kidney function

SGLT2 inhibitors become less effective for glucose lowering as kidney function declines, but their heart and kidney protective benefits may remain clinically important at lower eGFR levels.

The eGFR threshold differs by:

Specific medication
Indication
Whether the goal is glucose lowering, heart-failure treatment, or kidney protection

Do not memorize one renal cutoff for the entire class. Check the current indication-specific prescribing information.

Board pearl: Heart failure or chronic kidney disease should make you think about an SGLT2 inhibitor. Recurrent genital infections, dehydration, prolonged fasting, and risk of ketoacidosis require caution.

9. Alpha-Glucosidase Inhibitors

Examples include:

Acarbose
Miglitol

Mechanism of action

These drugs delay the digestion and absorption of carbohydrates in the small intestine, reducing postprandial glucose elevation.

Administration

They must be taken with the first bite of each main meal.

Common adverse effects

Flatulence
Abdominal discomfort
Diarrhea

GI effects are common because unabsorbed carbohydrates are fermented in the intestine.

Critical hypoglycemia rule

Alpha-glucosidase inhibitors do not usually cause hypoglycemia when used alone. However, if hypoglycemia occurs because the patient is also taking insulin or a sulfonylurea, it must be treated with:

Glucose
Dextrose
Glucagon when appropriate

Sucrose, or ordinary table sugar, may not work quickly enough because its breakdown is being delayed.

Board pearl: Acarbose is taken with the first bite of a meal. Treat associated hypoglycemia with glucose—not table sugar.

10. Insulin Therapy

Insulin is required for type 1 diabetes and may be needed at any stage of type 2 diabetes.

It has the greatest glucose-lowering capacity of all diabetes medications, but it also carries a significant risk of hypoglycemia.

Basal insulin

Basal insulin controls glucose between meals and overnight.

Examples include:

Insulin glargine
Insulin detemir
Insulin degludec
NPH insulin

Long-acting analogs generally have a flatter action profile than NPH. NPH has a pronounced peak and therefore a greater potential for hypoglycemia at predictable times.

Prandial insulin

Prandial insulin controls the glucose increase associated with meals.

Examples include rapid-acting formulations of:

Insulin lispro
Insulin aspart
Insulin glulisine

Regular insulin is short-acting but has a slower onset than rapid-acting analogs.

Correction insulin

Correction insulin treats glucose that is above the target range. It is different from prandial insulin, although a dose may include both mealtime coverage and correction.

Using correction insulin alone without basal or scheduled therapy—often called sliding-scale insulin—is generally reactive and does not address the patient’s underlying insulin requirements.

Major adverse effects

Hypoglycemia
Weight gain
Injection-site reactions
Lipohypertrophy
Hypokalemia, especially with higher doses or intravenous administration

Lipohypertrophy

Repeatedly injecting insulin into the same area can cause thickened fatty tissue. Insulin absorption from these areas becomes unpredictable.

Teach patients to:

Rotate injection sites
Avoid injecting into abnormal tissue
Use appropriate needle technique
Inspect injection sites regularly

Mixing insulin

Classic board-exam rules include:

NPH can be mixed with regular insulin.
Draw up clear insulin before cloudy insulin.
“Clear before cloudy.”
Long-acting insulins such as glargine and degludec should not be mixed with other insulins in the same syringe.

Insulin and potassium

Insulin drives both glucose and potassium into cells. This principle explains why insulin with dextrose may be used in emergency hyperkalemia treatment.

Board pearl: Insulin lowers potassium. Always think about hypokalemia when insulin is administered aggressively, especially intravenously.

Recognizing and Treating Hypoglycemia

Hypoglycemia is most strongly associated with:

Insulin
Sulfonylureas
Meglitinides

Symptoms may include:

Tremor
Sweating
Palpitations
Hunger
Anxiety
Dizziness
Confusion
Weakness
Behavioral changes
Seizures
Loss of consciousness

The 15-15 rule

For an alert patient who can safely swallow:

Give approximately 15 grams of fast-acting carbohydrate.
Recheck glucose after 15 minutes.
Repeat if glucose remains low.
Once corrected, provide a meal or snack when appropriate to prevent recurrence.

Examples of approximately 15 grams of carbohydrate include glucose tablets, glucose gel, or a measured amount of juice or regular soda.

Severe hypoglycemia

If the patient cannot safely swallow, treatment may include:

Glucagon outside the hospital
Intravenous dextrose when IV access is available
Emergency medical assistance

Teach family members and caregivers how and when to use prescribed glucagon.

High-Yield Medication Selection by Comorbidity

Patient with atherosclerotic cardiovascular disease

Consider an agent with demonstrated cardiovascular benefit, particularly an appropriate:

GLP-1 receptor agonist
SGLT2 inhibitor

The choice depends on the patient’s specific disease, kidney function, weight goals, tolerability, and the evidence for the individual medication.

Patient with heart failure

Think first about an SGLT2 inhibitor when appropriate.

Avoid or use significant caution with:

Thiazolidinediones
Saxagliptin
Alogliptin

Patient with chronic kidney disease

Consider an SGLT2 inhibitor with demonstrated kidney benefit when the patient meets indication-specific criteria.

A GLP-1 receptor agonist with appropriate evidence may also be considered, particularly when additional glycemic control, weight loss, or cardiovascular risk reduction is needed.

Remember:

Metformin is contraindicated at eGFR below 30 mL/min/1.73 m².
Many DPP-4 inhibitors require renal dose adjustment.
Linagliptin generally does not.
Glyburide should be avoided because of prolonged hypoglycemia risk.
SGLT2 initiation and continuation thresholds vary by medication and indication.

Patient with obesity or a major weight-loss goal

Consider:

A GLP-1 receptor agonist
A dual GIP/GLP-1 receptor agonist
An SGLT2 inhibitor when otherwise appropriate

Avoid or reconsider medications associated with weight gain when alternatives are available:

Sulfonylureas
Thiazolidinediones
Insulin

This does not mean insulin should be withheld when clinically necessary.

Patient at high risk of hypoglycemia

Favor medications with a low risk of hypoglycemia when used alone:

Metformin
SGLT2 inhibitors
GLP-1 receptor agonists
Tirzepatide
DPP-4 inhibitors
Thiazolidinediones
Alpha-glucosidase inhibitors

Use extra caution with:

Insulin
Sulfonylureas
Meglitinides

Patient with limited medication coverage

Lower-cost options may include:

Metformin
Sulfonylureas
Pioglitazone
Human insulins such as NPH and regular insulin

However, a lower purchase price does not automatically make a medication the safest or least expensive overall. Hypoglycemia, weight gain, monitoring requirements, and treatment of complications also matter.

Pregnancy and Diabetes Medications

Insulin is the traditional preferred medication for managing preexisting diabetes during pregnancy because it does not cross the placenta in clinically meaningful amounts and can be titrated precisely.

Some patients with gestational diabetes may be managed with other approaches depending on the clinical situation and specialist guidance, but several newer agents lack adequate pregnancy safety data.

Patients who are pregnant or planning pregnancy should have their complete medication regimen reviewed promptly.

Board pearl: When a question asks for the most established pharmacologic treatment for diabetes during pregnancy, think insulin.

Sick-Day Medication Safety

Acute illness can change the safety of diabetes medications.

During vomiting, diarrhea, dehydration, reduced oral intake, severe infection, or another acute illness, reassess medications that may increase the risk of:

Hypoglycemia
Dehydration
Acute kidney injury
Lactic acidosis
Ketoacidosis

Medications that may require temporary interruption in selected circumstances include:

Metformin during significant dehydration, hypoxia, or acute kidney injury
SGLT2 inhibitors during acute illness, fasting, dehydration, or ketosis risk
Sulfonylureas or meglitinides when the patient cannot eat
Insulin doses when intake changes—although basal insulin should not be casually stopped, particularly in type 1 diabetes

Patients with type 1 diabetes must continue receiving insulin during illness. They may need dose adjustments, additional monitoring, ketone testing, hydration, and urgent medical evaluation.

Board-Style Medication Clues

Clinical clue	Most likely medication or class
Decreases hepatic glucose production	Metformin
Recurrent prolonged hypoglycemia in an older adult with CKD	Glyburide
Taken before meals and skipped when the meal is skipped	Meglitinide
Edema and worsening heart failure	Thiazolidinedione
Oral, weight-neutral, low hypoglycemia risk	DPP-4 inhibitor
No routine renal dose adjustment	Linagliptin
Weight loss and delayed gastric emptying	GLP-1 receptor agonist
Activates GIP and GLP-1 receptors	Tirzepatide
Genital fungal infections and euglycemic DKA	SGLT2 inhibitor
Taken with the first bite of a meal	Acarbose
Greatest glucose-lowering capacity	Insulin
“Clear before cloudy”	Regular insulin before NPH
Must be stopped several days before surgery	SGLT2 inhibitor

Common FNP Board Traps

Trap 1: “Metformin is always first-line”

Metformin is appropriate for many patients, but treatment must be individualized. Comorbid heart failure, CKD, cardiovascular disease, severe hyperglycemia, weight goals, and cost may change the initial plan.

Trap 2: “All diabetes medications cause hypoglycemia”

The greatest risk comes from insulin, sulfonylureas, and meglitinides. Most other classes have a low risk when used alone.

Trap 3: “All GLP-1 medications are contraindicated with any thyroid disease”

The specific contraindication concerns a personal or family history of medullary thyroid carcinoma or MEN2—not routine hypothyroidism or Hashimoto thyroiditis.

Trap 4: “A normal glucose level rules out DKA”

SGLT2 inhibitors can cause euglycemic DKA. Evaluate the symptoms, anion gap, bicarbonate, pH, and ketones rather than relying on glucose alone.

Trap 5: “Every low eGFR means the same thing for every medication”

Renal dosing is drug-specific. Metformin, SGLT2 inhibitors, sulfonylureas, and DPP-4 inhibitors have different considerations.

Trap 6: “Injectable therapy always means insulin”

Most GLP-1 receptor agonists and tirzepatide are injectable but are not insulin.

Trap 7: “Insulin should be avoided because it causes weight gain”

Insulin should never be withheld when it is clinically necessary. Safety and metabolic stabilization come first.

Final Diabetes Pharmacology Checklist

Before taking your FNP boards, make sure you can answer the following:

Which medications are most likely to cause hypoglycemia?
Which medications promote weight loss?
Which class is particularly useful in heart failure?
Which classes may provide cardiovascular or kidney benefits?
At what eGFR is metformin contraindicated?
Which sulfonylurea should generally be avoided in CKD and older adults?
Which DPP-4 inhibitor generally does not require renal dose adjustment?
Which medication classes slow gastric emptying?
Which medications are associated with euglycemic DKA?
Which class can worsen heart failure through fluid retention?
Which medications should be held before surgery?
When should insulin be considered immediately?
How should conscious and unconscious hypoglycemia be treated?

The key to mastering diabetes medications is not memorizing a long list of drug names. It is learning to connect each medication with the patient who would benefit from it—and the patient who could be harmed by it.

When you see a diabetes pharmacology question, ask yourself:

What does this patient need beyond a lower A1C?

That one question will help you identify the safest and most clinically appropriate answer.

Ready to turn diabetes pharmacology into board-exam confidence? The FNP Review combines high-yield teaching, board-style practice questions, detailed rationales, readiness tracking, and a personalized study system to help you prepare for the AANP and ANCC certification exams.

This article is intended for education and board review. Medication selection, dosing, contraindications, and perioperative instructions should be confirmed using current prescribing information, clinical guidelines, patient-specific factors, and institutional protocols.