What is the best approach for a patient with type 2 diabetes and overweight/obesity starting on Trulicity (dulaglutide) 1.5 mg?

Starting Trulicity 1.5 mg for Type 2 Diabetes with Overweight/Obesity

Begin with Trulicity 0.75 mg subcutaneously once weekly, then increase to 1.5 mg once weekly after 4 weeks for additional glycemic control. 1

Initial Dosing Protocol

• Start at 0.75 mg once weekly subcutaneously, not 1.5 mg directly, as this is the FDA-approved starting dose that minimizes gastrointestinal side effects while establishing tolerance 1
• Administer the injection at any time of day, with or without food, in the abdomen, thigh, or upper arm 1
• Escalate to 1.5 mg once weekly after at least 4 weeks on the starting dose if additional glycemic control is needed 1
• If further intensification is required after 4 weeks on 1.5 mg, increase in 1.5 mg increments (to 3 mg, then 4.5 mg maximum) 1

Foundation Therapy Requirements

• Continue metformin unless contraindicated, as it remains the cornerstone of type 2 diabetes therapy and provides complementary glucose-lowering effects when combined with GLP-1 receptor agonists 2
• Metformin should be optimized to at least 1000 mg twice daily (2000 mg total daily dose) for maximum effectiveness 2
• When choosing glucose-lowering medications for patients with type 2 diabetes and overweight or obesity, prioritize medications that promote weight loss or are weight-neutral 2

Expected Clinical Benefits

• Dulaglutide 1.5 mg consistently produces 3-5% weight loss from baseline, which is clinically meaningful for patients with overweight or obesity 2
• HbA1c reductions of approximately 1.0-1.5% can be expected when added to metformin or other oral agents 3, 4, 5
• The medication provides cardiovascular risk reduction in patients with established cardiovascular disease or multiple risk factors 1
• Dulaglutide has a low inherent risk of hypoglycemia when used without insulin or sulfonylureas 3, 6

Critical Safety Considerations and Contraindications

• Absolutely contraindicated in patients with personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) 1
• Contraindicated in patients with serious hypersensitivity reactions to dulaglutide 1
• Do not use in patients with a history of pancreatitis—consider alternative therapies instead 1, 7
• Not recommended in patients with severe gastrointestinal disease or severe gastroparesis 1
• Not appropriate for type 1 diabetes mellitus 1

Managing Gastrointestinal Side Effects

• Nausea (15-52%), diarrhea (6-10%), and vomiting (3-4%) are the most common adverse effects, typically occurring early in treatment and diminishing over time 3, 6, 5
• Starting at 0.75 mg rather than 1.5 mg significantly reduces the incidence of gastrointestinal symptoms (5% vs 15% nausea rate) 5
• Counsel patients that these symptoms usually improve within 2-4 weeks as tolerance develops 3, 6
• If gastrointestinal symptoms are intolerable, consider remaining at 0.75 mg rather than escalating to 1.5 mg 1

Combination Therapy Considerations

• Dulaglutide can be safely combined with SGLT2 inhibitors (such as empagliflozin) and metformin, as these agents work through complementary mechanisms 5
• When combined with SGLT2 inhibitors, dulaglutide produces additional HbA1c reductions of 0.66-0.79% beyond the SGLT2 inhibitor effect 5
• If using dulaglutide with insulin, administer as separate injections and never mix—injections can be in the same body region but not adjacent to each other 1
• The combination of basal insulin plus GLP-1 receptor agonist provides potent glucose-lowering with less weight gain and hypoglycemia than intensified insulin regimens 2

Patient Education Essentials

• Train on proper injection technique using the single-dose pen device before the first dose 1
• Rotate injection sites with each weekly dose to prevent lipohypertrophy 1
• Inspect the solution before use—it should be clear and colorless; do not use if particulate matter or discoloration is present 1
• If a dose is missed, administer as soon as possible only if at least 3 days (72 hours) remain until the next scheduled dose; otherwise skip and resume the regular schedule 1
• Counsel patients about symptoms of thyroid tumors (neck mass, dysphagia, dyspnea, persistent hoarseness) and instruct them to report these immediately 1

Monitoring Requirements

• Check HbA1c every 3 months during dose titration to assess glycemic response 2
• Monitor weight at each visit, as weight loss is a key therapeutic benefit 2
• Assess for gastrointestinal symptoms at follow-up visits, particularly in the first 4-8 weeks 3, 6
• Routine monitoring of serum calcitonin or thyroid ultrasound is of uncertain value and not recommended for early MTC detection 1

Common Pitfalls to Avoid

• Do not start directly at 1.5 mg—this increases gastrointestinal side effects and may lead to treatment discontinuation 1, 5
• Do not discontinue metformin when adding dulaglutide unless there is a specific contraindication 2
• Do not delay escalation beyond 4 weeks if glycemic control remains inadequate on 0.75 mg 1
• Do not use in patients with a history of pancreatitis, as this significantly increases the risk of acute pancreatitis 1, 7
• Do not prescribe for patients with personal or family history of MTC or MEN 2 syndrome 1