What is the difference between Trulicity (dulaglutide) and Actos (pioglitazone) for managing Diabetes Mellitus (DM)?

Differences Between Actos (Pioglitazone) and Trulicity (Dulaglutide) for Diabetes Mellitus

Trulicity (dulaglutide) is a once-weekly injectable GLP-1 receptor agonist that provides superior glycemic control compared to Actos (pioglitazone), which is an oral thiazolidinedione with insulin-sensitizing effects but carries risks of heart failure, weight gain, and fractures. 1

Mechanism of Action

• Trulicity (dulaglutide): Acts as a GLP-1 receptor agonist that stimulates insulin secretion in a glucose-dependent manner, reduces glucagon secretion, improves satiety, and slows gastric emptying 2, 3
• Actos (pioglitazone): Functions as a thiazolidinedione (TZD) that increases insulin sensitivity in peripheral tissues and has high glucose-lowering efficacy 1

Efficacy

• Trulicity has demonstrated superior glycemic control compared to many oral agents, reducing HbA1c by approximately 0.7-1.5%, with consistent reductions in body weight 2, 3
• Actos provides high glucose-lowering efficacy but is associated with weight gain rather than weight loss 1
• In comparative studies, GLP-1 receptor agonists like dulaglutide have shown better glycemic control than oral agents including thiazolidinediones 3

Cardiovascular Effects

• Trulicity has demonstrated cardiovascular benefits in patients with established atherosclerotic cardiovascular disease, reducing major adverse cardiovascular events (MACE) with a hazard ratio of 0.88 (95% CI 0.79,0.99) 1
• Actos has been associated with increased risk for heart failure and should not be used in patients with heart failure 1
• The 2019 ESC/EASD guidelines specifically state that thiazolidinediones (pioglitazone and rosiglitazone) are not recommended in heart failure 1

Weight Effects

• Trulicity promotes weight loss, which is beneficial for most patients with type 2 diabetes 2, 3
• Actos causes weight gain, which can be undesirable in patients with type 2 diabetes who are often already overweight or obese 1

Administration

• Trulicity is administered as a once-weekly subcutaneous injection, which may improve adherence for some patients 2, 4
• Actos is taken orally once daily, which some patients may prefer over injections 1

Safety Considerations

Trulicity (dulaglutide)

• Low risk of hypoglycemia when used as monotherapy 2, 4
• Most common side effects are gastrointestinal (nausea, vomiting, diarrhea) 2, 5
• Rare cases of pancreatitis have been reported 5
• No dose adjustment needed for mild to moderate renal impairment 3

Actos (pioglitazone)

• Associated with fluid retention, edema, and increased risk of heart failure 1
• Increased risk of fractures, particularly in women 1
• May be used with caution to improve glucose control and reduce total daily insulin dose, but not recommended in heart failure 1
• Contraindicated in patients with active bladder cancer or history of bladder cancer 1

Current Guideline Recommendations

• For patients with established atherosclerotic cardiovascular disease or high cardiovascular risk, GLP-1 receptor agonists like Trulicity are recommended to reduce cardiovascular events 1
• For patients with heart failure or chronic kidney disease, SGLT2 inhibitors are preferred, while both TZDs and GLP-1 receptor agonists have specific places in therapy 1
• The 2019 ADA/EASD consensus report recommends GLP-1 receptor agonists as preferred second-line therapy after metformin for patients with established ASCVD where MACE is the gravest threat 1
• Thiazolidinediones like Actos are generally considered later-line options due to their side effect profile 1

Common Pitfalls and Considerations

• Avoid Actos in patients with heart failure, history of bladder cancer, or high fracture risk 1
• Monitor for pancreatitis with Trulicity, especially in patients with a history of pancreatitis 5
• Consider patient preferences regarding injection versus oral administration, as this may impact adherence 2, 4
• Be aware of cost differences, as Trulicity is typically more expensive than generic pioglitazone 3
• Consider cardiovascular risk profile of the patient when choosing between these medications, as Trulicity offers cardiovascular benefits while Actos increases heart failure risk 1