What is the recommended treatment approach for a patient with type 2 diabetes using Trulicity (dulaglutide)?

Trulicity (Dulaglutide) Treatment Approach for Type 2 Diabetes

Primary Indication and Positioning

Trulicity is a once-weekly GLP-1 receptor agonist indicated as an adjunct to diet and exercise for improving glycemic control in adults and pediatric patients ≥10 years with type 2 diabetes, and for reducing major adverse cardiovascular events in adults with established cardiovascular disease or multiple cardiovascular risk factors. 1

When to Initiate Trulicity

Add Trulicity as a preferred second-line agent after metformin when patients have not achieved individualized glycemic targets, particularly if they have established atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease. 2

• The ADA/KDIGO consensus specifically recommends adding a long-acting GLP-1 receptor agonist like dulaglutide for patients not achieving glycemic targets despite metformin and/or SGLT2 inhibitor therapy 2
• Dulaglutide has demonstrated cardiovascular benefit in large outcome trials, with evidence showing reduction in major adverse cardiovascular events (MACE) 2
• The cardiovascular benefit was similar between those with and without previous cardiovascular or kidney disease 2

Dosing and Administration

Starting Dose

• Initiate Trulicity at 0.75 mg subcutaneously once weekly 1
• The dose can be increased to 1.5 mg once weekly for additional glycemic control 1
• Administer at the same time each week, regardless of meals 1
• Can be injected in the abdomen, thigh, or upper arm with no difference in pharmacokinetics 3

Dose Titration

• If additional glycemic control is needed after starting at 0.75 mg, increase to 1.5 mg once weekly 1
• The 1.5 mg dose provides greater HbA1c reduction (approximately 1.1-1.3% reduction) compared to 0.75 mg (approximately 0.8-1.2% reduction) 1
• Steady state is achieved between the second and fourth doses 3

Renal Dosing Considerations

No dose adjustment is required for dulaglutide across all levels of renal function, including patients with chronic kidney disease. 2

• This is a significant advantage over other GLP-1 receptor agonists like exenatide and lixisenatide, which have renal restrictions 2
• Dulaglutide can be used safely in patients with eGFR <45 mL/min/1.73 m² 2
• In a glycemic efficacy and safety trial in patients with moderate-to-severe CKD (stages G3 and G4), dulaglutide produced similar glycemic control to insulin glargine but resulted in significantly slower GFR decline 2

Combination Therapy Strategies

With Metformin (Foundation Therapy)

• Continue metformin at maximum tolerated dose (up to 2000-2550 mg daily) when adding Trulicity 2, 4
• The combination provides superior glycemic control with complementary mechanisms of action 4

With SGLT2 Inhibitors

• Trulicity can be added to SGLT2 inhibitor therapy (with or without metformin) for patients with inadequate glycemic control 1, 5
• In the AWARD-10 trial, adding dulaglutide 1.5 mg to SGLT2 inhibitors resulted in HbA1c reduction of -1.34% vs -0.54% with placebo (difference -0.79%, p<0.0001) 5
• This combination addresses hyperglycemia through complementary mechanisms: SGLT2 inhibitors increase urinary glucose excretion while GLP-1 receptor agonists enhance insulin secretion and suppress glucagon 5

With Basal Insulin

• Trulicity can be added to basal insulin (with or without metformin) when basal insulin alone is insufficient 1
• In the AWARD-9 trial, adding dulaglutide 1.5 mg to titrated insulin glargine resulted in HbA1c reduction of -1.5% vs -0.6% with placebo 1
• This combination is preferred over advancing to basal-bolus insulin regimens, as it provides comparable or better HbA1c reduction with lower hypoglycemia risk and weight loss rather than weight gain 6

Discontinue DPP-4 Inhibitors

• Always discontinue any DPP-4 inhibitor before starting Trulicity 2
• Both agents work through the incretin pathway, and combining them provides no additional benefit 2

Sulfonylurea Management

• If HbA1c is well-controlled at baseline or there is a history of frequent hypoglycemic events, wean or stop sulfonylurea when starting Trulicity 2
• Consider reducing total daily insulin dose by approximately 20% when starting Trulicity if the patient is on insulin 2

Expected Efficacy

Glycemic Control

• Trulicity 1.5 mg once weekly reduces HbA1c by approximately 0.8-1.5% depending on baseline values and combination therapy 1, 7
• The 0.75 mg dose reduces HbA1c by approximately 0.7-1.2% 1
• Fasting serum glucose reductions range from 16-30 mg/dL 1

Weight Effects

• Trulicity 1.5 mg consistently produces weight loss of approximately 2-3 kg 1, 7
• The 0.75 mg dose produces more modest weight loss of approximately 1-2.5 kg 1
• Weight loss is maintained during long-term treatment up to 2 years 7

Cardiovascular Benefits

• Dulaglutide reduces risk of major adverse cardiovascular events in patients with type 2 diabetes 2
• The MACE risk reduction with GLP-1 receptor agonists was significantly greater for those with eGFR <60 mL/min/1.73 m² than for those with eGFR ≥60 mL/min/1.73 m² 2

Renal Benefits

• Dulaglutide reduces albuminuria and slows eGFR decline 2
• In a meta-analysis of 8 cardiovascular outcomes trials, GLP-1 receptor agonists significantly reduced risk for a composite kidney disease outcome (macroalbuminuria, eGFR decline, progression to kidney failure, or death from kidney disease) 2

Monitoring and Patient Education

Initial Monitoring

• Instruct patients to more closely monitor glucose at home for the first 4 weeks of therapy 2
• Check HbA1c every 3 months until target achieved, then every 6 months if stable 4

Mitigating Gastrointestinal Side Effects

• To minimize nausea, recommend small portion sizes for meals, start at the lowest dose (0.75 mg), and up-titrate as tolerated toward the goal dose of 1.5 mg 2
• The most frequently reported adverse events are gastrointestinal-related (nausea, vomiting, diarrhea), which are typically transient 7, 8
• Nausea occurs in approximately 15% of patients on the 1.5 mg dose 5

Ophthalmologic Monitoring

• Advise patients to undergo appropriate, guideline-recommended eye examinations before starting therapy if not done within the last 12 months 2
• Discuss potential risk of diabetic retinopathy complications with dulaglutide 2

Hypoglycemia Risk

• Trulicity has a low inherent risk of hypoglycemia when used alone or with metformin 7
• Hypoglycemia risk increases when combined with sulfonylureas or insulin 2

Critical Contraindications and Precautions

Absolute Contraindications

• Do not use Trulicity in patients with type 1 diabetes mellitus 1
• Avoid in patients with severe gastrointestinal disease, including severe gastroparesis 1
• Avoid in patients with active gallbladder disease 2

Relative Contraindications

• Trulicity has not been studied in patients with a history of pancreatitis; consider other antidiabetic therapies in these patients 1
• Avoid in patients with diabetic gastroparesis 2

Common Pitfalls to Avoid

Delaying GLP-1 Receptor Agonist Therapy

• Do not delay adding Trulicity in patients with cardiovascular disease, heart failure, or CKD who are not achieving glycemic targets on metformin alone 2
• SGLT2 inhibitors and GLP-1 receptor agonists provide mortality benefit beyond glucose lowering in these populations 4

Inappropriate Insulin Intensification

• Do not continue escalating basal insulin beyond 0.5-1.0 units/kg/day without considering adding Trulicity instead of prandial insulin 6
• The combination of basal insulin plus GLP-1 receptor agonist provides potent glucose-lowering with superior outcomes compared to basal-bolus insulin regimens 6

Inadequate Metformin Optimization

• Do not add Trulicity before optimizing metformin to at least 1500-2000 mg daily, unless contraindicated 4
• Metformin remains the foundation of type 2 diabetes therapy and should be continued at maximum tolerated dose 2

Ignoring Cardiovascular and Renal Comorbidities

• Never ignore cardiovascular and renal comorbidities when selecting therapy; SGLT2 inhibitors and GLP-1 receptor agonists like Trulicity provide mortality benefit beyond glucose lowering 4
• For patients with established ASCVD, heart failure, or CKD, prioritize agents with proven cardiovascular and renal benefits 2