What tests and evaluations are required for a patient with type 2 diabetes before starting retatrutide (a glucagon-like peptide-1 (GLP-1) receptor agonist) treatment?

Pre-Treatment Testing for Retatrutide

Before starting retatrutide in patients with type 2 diabetes, obtain baseline HbA1c, comprehensive metabolic panel including renal function, and ensure an ophthalmology examination has been completed within the past 12 months, particularly given the GLP-1 receptor agonist class association with diabetic retinopathy complications.

Essential Laboratory Testing

Baseline Glycemic Assessment

• Measure HbA1c to establish baseline glycemic control and guide treatment targets 1
• Monitor glucose levels at baseline, as retatrutide trials enrolled patients with HbA1c of 7.0-10.5% 1
• Plan for glucose monitoring with each treatment cycle during the first 4 weeks, especially if the patient is on insulin, sulfonylureas, or glinides 2

Renal Function Evaluation

• Obtain baseline estimated glomerular filtration rate (eGFR) and serum creatinine 3
• This is critical because retatrutide, like other GLP-1 receptor agonists, requires assessment of kidney function for appropriate patient selection 3
• Consider baseline natriuretic peptide (BNP or NT-proBNP) testing in patients at risk for heart failure to facilitate cardiovascular risk stratification 3

Cardiovascular Risk Assessment

• Assess for established atherosclerotic cardiovascular disease (ASCVD) through history and physical examination, as this influences treatment selection and monitoring 3
• Consider baseline lipid panel if not recently obtained, as cardiovascular risk reduction is a key treatment goal 3

Required Clinical Evaluations

Ophthalmologic Examination

• Ensure guideline-recommended eye examination within the past 12 months before initiating retatrutide 2
• This is particularly important because GLP-1 receptor agonists, specifically semaglutide, have been associated with increased risk of diabetic retinopathy complications, predominantly in patients with prior proliferative retinopathy 2
• Patients with any degree of macular edema, severe nonproliferative diabetic retinopathy, or proliferative diabetic retinopathy should be referred to an experienced ophthalmologist 3

Contraindication Screening

• Screen for history of medullary thyroid cancer or multiple endocrine neoplasia type 2 (MEN2), which are contraindications to GLP-1 receptor agonist therapy 3
• Assess for active gallbladder disease, as GLP-1 receptor agonists may increase risk of acute cholecystitis 2
• Evaluate for diabetic gastroparesis, which is a relative contraindication to GLP-1 receptor agonist use 2
• Screen for history of pancreatitis, as this may influence risk-benefit assessment 2

Medication Reconciliation and Adjustment

Discontinue Incompatible Medications

• Stop DPP-4 inhibitors immediately before starting retatrutide, as both work through the incretin pathway and their combination is pharmacologically redundant 4, 2
• No washout period or gradual taper is needed for DPP-4 inhibitor discontinuation 4

Adjust Hypoglycemia-Risk Medications

• For patients with well-controlled HbA1c or history of frequent hypoglycemia: wean or stop sulfonylureas and consider reducing total daily insulin dose by approximately 20% 3, 2
• For patients on glinides: consider discontinuing these agents or reducing doses by 50% to prevent hypoglycemia 4
• This is critical because retatrutide demonstrated robust glucose-lowering efficacy in phase 2 trials, with HbA1c reductions up to 2.02% at the 12 mg dose 1

Patient Education and Monitoring Plan

Initial Monitoring Strategy

• Instruct patients to monitor glucose more frequently during the first 4 weeks of therapy, especially if on insulin, sulfonylureas, or glinides 2
• Plan for HbA1c reassessment at 3 months to evaluate treatment response 3
• Monitor for gastrointestinal adverse events, as these were the most frequently reported side effects in retatrutide trials (occurring in 35% of participants) 1

Safety Education

• Educate patients regarding symptoms of diabetic ketoacidosis (nausea, vomiting, abdominal pain, weakness), noting that it can occur even with blood glucose readings in the 150-250 mg/dL range 3
• Counsel on symptoms of dehydration (lightheadedness, orthostasis, weakness) and instruct patients to hold medication if experiencing low oral intake 3
• Provide education on genital hygiene to reduce risk of mycotic infections 3

Common Pitfalls to Avoid

• Do not continue DPP-4 inhibitors when starting retatrutide—this is explicitly contraindicated and provides no additional benefit 4
• Do not skip ophthalmology evaluation in patients who have not had recent eye examinations, particularly those with known retinopathy 2
• Do not fail to reduce insulin or sulfonylurea doses in patients with well-controlled glucose, as this significantly increases hypoglycemia risk given retatrutide's potent glucose-lowering effects 2, 1
• Do not initiate retatrutide in patients with active gallbladder disease or gastroparesis without careful risk-benefit assessment 2