SemaglutidePA study guide

Why they happen and how to manage them

Nausea, vomiting, early satiety

GLP-1 receptor activation slows gastric emptying and acts on central satiety pathways. Management: Titrate slowly as labeled, eat smaller meals, and stop eating when full.

Acute kidney injury

Vomiting and diarrhea cause dehydration and prerenal injury. Management: Encourage fluids and check renal function when GI losses are significant.

Hypoglycemia

Insulin release is glucose-dependent, so risk is low alone but rises when insulin or a sulfonylurea adds glucose-independent insulin effect. Management: Lower the insulin or sulfonylurea dose when starting.

Gallbladder disease

Rapid weight loss and reduced gallbladder motility favor gallstone formation. Management: Evaluate right upper quadrant pain with gallbladder studies.

Worsening retinopathy

Rapid improvement in glucose control can transiently worsen existing diabetic retinopathy. Management: Monitor patients with known retinopathy and ask about vision changes.

Aspiration with anesthesia

Delayed gastric emptying leaves residual stomach contents despite fasting. Management: Make sure the anesthesia team knows the patient takes a GLP-1 receptor agonist.

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Common and serious

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Narrow therapeutic index

The label does not describe a narrow therapeutic index or direct dosing by measured blood levels of the drug.

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Blood glucose

Why

Hypoglycemia with insulin or a sulfonylurea

When

When starting and with dose changes

Act on

Consider lowering the insulin or sulfonylurea dose

Normal

Fasting 70 to 99 mg/dL.

Sources: [1][2][3]

Hemoglobin A1c

Why

Glycemic response

When

After dose changes; escalate after at least 4 weeks on a dose

Act on

If more glycemic control is needed, step up the dose

Normal

Below 5.7% is normal and 6.5% or higher indicates diabetes. Many people with diabetes aim for below 7%.

Sources: [1][2]

Serum creatinine

Why

Acute kidney injury from volume depletion

When

When GI effects could cause dehydration, especially during initiation and escalation

Normal

0.7 to 1.3 mg/dL in men and 0.5 to 0.95 mg/dL in women.

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Adult dose

Start (all indications)

0.25 mg subcutaneously once weekly for 4 weeks to limit GI effects, then 0.5 mg once weekly.

Glycemic control

Maintenance 0.5 mg, 1 mg, or 2 mg once weekly. If more control is needed, increase to 1 mg after at least 4 weeks on 0.5 mg, then to 2 mg after at least 4 weeks on 1 mg. Maximum 2 mg once weekly.

Type 2 diabetes with chronic kidney disease

Increase to the 1 mg once-weekly maintenance dose after at least 4 weeks on 0.5 mg.

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Renal adjustment

None, including kidney failure. Monitor renal function when GI effects could cause volume depletion, especially during initiation and escalation.

Sources: [1][2]

Hepatic adjustment

None. Hepatic impairment did not change exposure in a clinically relevant way.

Sources: [1]

Boxed warning

Risk of thyroid C-cell tumors. Semaglutide causes these tumors in rodents; whether it causes medullary thyroid carcinoma in humans is unknown. Contraindicated with a personal or family history of MTC or with MEN 2. Teach patients to report a neck mass, trouble swallowing, shortness of breath, or lasting hoarseness.

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Contraindications

• Personal or family history of medullary thyroid carcinoma (MTC)
• Multiple endocrine neoplasia syndrome type 2 (MEN 2)
• Prior serious hypersensitivity to semaglutide or any excipient

Sources: [1]

Key interactions

Insulin or insulin secretagogues such as sulfonylureas

Higher risk of hypoglycemia, including severe episodes. Consider lowering the insulin or sulfonylurea dose when starting.

Oral medications

Delayed gastric emptying may change their absorption. Use with caution, especially for drugs with a narrow therapeutic range.

Sources: [1][2]

Antidote or reversal

No specific antidote. Give supportive care based on symptoms, such as nausea, vomiting, and hypoglycemia. Observation may need to be prolonged because the half-life is about 1 week.

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Pregnancy

Human data are limited; animal studies suggest possible fetal risk. Use only if the benefit justifies the risk. Poorly controlled diabetes also harms mother and fetus. Stop at least 2 months before a planned pregnancy because of the long washout.

Sources: [1][2]

Lactation

No human data on semaglutide in breast milk. It appears in rat milk. Weigh the benefits of breastfeeding against the mother's need for the drug.

Sources: [1]

Pediatric

Safety and efficacy have not been established in children.

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Geriatric

No overall differences in safety or efficacy in patients 65 and older, but some older adults may be more sensitive.

Sources: [1]