What are the necessary considerations and steps when initiating a Glucagon-like peptide-1 (GLP-1) analogue in a typical adult patient with type 2 diabetes?

Essential Steps When Initiating GLP-1 Receptor Agonist Therapy

When starting a GLP-1 receptor agonist, you must discontinue any DPP-4 inhibitor, adjust doses of insulin or sulfonylureas to prevent hypoglycemia, start at the lowest dose with gradual titration to minimize gastrointestinal side effects, and ensure patients have had appropriate eye examinations within the past 12 months. 1, 2

Pre-Initiation Screening and Contraindications

Before prescribing a GLP-1 RA, you must screen for absolute contraindications:

• Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2) - these are absolute contraindications per FDA labeling 3, 4
• Active gallbladder disease - avoid initiation in these patients 1
• History of gastroparesis - GLP-1 RAs delay gastric emptying and will worsen this condition 1, 2
• History of pancreatitis - while not an absolute contraindication per all guidelines, exercise extreme caution and consider alternative therapy 3, 4
• Proliferative diabetic retinopathy - use caution particularly with semaglutide or dulaglutide 1

Medication Adjustments Before Starting

Discontinue DPP-4 Inhibitors

You must stop any DPP-4 inhibitor (sitagliptin, saxagliptin, linagliptin, alogliptin) before starting a GLP-1 RA - there is no additional glucose-lowering benefit from combining these agents, and both work through the incretin pathway 1, 2

Adjust Hypoglycemia-Risk Medications

If the patient's HbA1c is well-controlled at baseline or they have a history of frequent hypoglycemic events 1, 2:

• Sulfonylureas: Reduce dose by 50% or discontinue entirely 2
• Basal insulin: Consider reducing total daily dose by approximately 20% 1, 2
• Glinides (meglitinides): Consider discontinuing 1

Continue These Medications

• Metformin: Continue at current dose - provides complementary glucose-lowering mechanisms 1
• SGLT2 inhibitors: Continue if already prescribed - these provide additive cardiovascular and renal benefits 1

Dosing and Titration Strategy

Starting Dose

Always start at the lowest available dose to minimize gastrointestinal side effects 1, 2:

• Liraglutide (Victoza): Start at 0.6 mg subcutaneously once daily for one week 3
• Semaglutide (Ozempic): Start at 0.25 mg subcutaneously once weekly for 4 weeks 4
• Dulaglutide: Start at 0.75 mg subcutaneously once weekly 2

Titration Schedule

Increase doses gradually toward the goal doses used in cardiovascular outcome trials 1:

• Liraglutide: After 1 week at 0.6 mg, increase to 1.2 mg daily. If additional glycemic control is needed after at least 1 week, increase to 1.8 mg daily 3
• Semaglutide: After 4 weeks at 0.25 mg, increase to 0.5 mg weekly. If additional glycemic control is needed after at least 4 weeks, increase to 1 mg weekly 4

Patient Education Requirements

Gastrointestinal Side Effects Management

Educate patients that nausea, vomiting, and diarrhea are common but typically improve over time 1:

• Recommend small portion sizes at meals to mitigate nausea 1
• Take daily GLP-1 RAs (liraglutide, lixisenatide) before meals 1
• Once-weekly GLP-1 RAs can be taken at any time regardless of meals 1
• If side effects persist beyond a few weeks, follow up with healthcare provider 1

Injection Technique

• Inject subcutaneously in the abdomen, thigh, or upper arm 3, 4, 3
• Administer at any time of day, independently of meals (for liraglutide) 3
• When using with insulin, administer as separate injections - never mix 3
• Never share pens between patients, even if the needle is changed 3, 4

Hypoglycemia Recognition

Instruct patients to monitor glucose more closely during the first 4 weeks of therapy, especially if taking insulin, sulfonylureas, or glinides 1, 2:

• Carry a source of quick-acting carbohydrates (glucose tablets, juice) at all times 1
• If hypoglycemia occurs while on α-glucosidase inhibitors, use glucose tablets specifically - these drugs prevent digestion of complex carbohydrates 1

Monitoring Requirements

Initial Monitoring Period

• Instruct patients to monitor blood glucose more closely at home for the first 4 weeks of therapy 1, 2
• Check HbA1c every 3 months to assess treatment effectiveness 5

Ophthalmologic Monitoring

Ensure patients undergo appropriate guideline-recommended eye examinations before starting therapy if not done within the last 12 months 1, 2. This is particularly important because:

• Rapid improvement in glucose control can temporarily worsen diabetic retinopathy 1, 2
• Semaglutide and dulaglutide have been associated with diabetic retinopathy complications in clinical trials 1, 4

Renal Function Monitoring

Use caution when initiating or escalating doses in patients with renal impairment, as acute kidney injury has been reported postmarketing, usually associated with nausea, vomiting, diarrhea, or dehydration 3, 4

Perioperative Management

Instruct patients to inform healthcare providers of any planned surgeries or procedures 3. GLP-1 RAs delay gastric emptying, which increases the risk of pulmonary aspiration during general anesthesia or deep sedation 2, 3:

• Consider appropriate aspiration risk reduction strategies, including point-of-care gastric ultrasound assessment before induction of anesthesia 2
• For elective procedures, weigh the benefits of continuing glycemic control against aspiration risks 2

Special Considerations for Specific Patient Populations

Patients with Established Cardiovascular Disease

If the patient has established atherosclerotic cardiovascular disease, choose a GLP-1 RA with proven cardiovascular benefit: liraglutide, semaglutide, or dulaglutide 1, 2

Patients with Chronic Kidney Disease

GLP-1 RAs are effective regardless of kidney function and have beneficial effects on cardiovascular, mortality, and kidney outcomes 1. Semaglutide specifically has demonstrated benefits in dedicated CKD trials 1

Pregnancy Planning

Discontinue GLP-1 RAs in women at least 2 months before a planned pregnancy due to the long washout period for semaglutide 4

Common Pitfalls to Avoid

• Do not combine GLP-1 RAs with DPP-4 inhibitors - no added benefit and unnecessary cost 1, 2
• Do not start at high doses - this dramatically increases gastrointestinal side effects and leads to discontinuation 1, 2
• Do not forget to reduce sulfonylurea or insulin doses - this leads to hypoglycemia 1, 2
• Do not prescribe in patients with personal/family history of MTC or MEN2 - absolute contraindication 3, 4
• Do not ignore persistent gastrointestinal symptoms beyond a few weeks - may indicate need for dose reduction or alternative therapy 1