KEY POINTS IN EVIDENCE-JUNE 2015.

For reducing HbA1c levels in people with type 2 diabetes, dulaglutide once weekly, when added to metformin, was statistically superior to exenatide twice daily (both in combination with pioglitazone), statistically superior to sitagliptin and statistically non?inferior to liraglutide 1.8 mg daily.
As with the other glucagon?like peptide?1 (GLP?1) receptor agonists there are limited data from randomised controlled trials (RCTs) on the effect of dulaglutide on patient?oriented outcomes, such as rates of macrovascular or microvascular events, or on long?term safety.

Regulatory status: Dulaglutide (Trulicity) received a European marketing authorisation in November 2014 and was launched in the UK in January 2015.

Effectiveness

Dulaglutide 1.5 mg or 0.75 mg once weekly was superior to placebo (treatment difference ?11.5 mmol/mol [­1.05% points] and ?9.2 mmol/mol [­0.84% points], respectively) and to exenatide twice daily (treatment difference ?5.7 mmol/mol [­0.52% points] and ?3.4 mmol/mol [­0.31% points], respectively) for change in HbA1c from baseline (1 RCT, n=978, 26 weeks).

Dulaglutide 1.5 mg or 0.75 mg once weekly was superior to sitagliptin once daily (treatment difference ?7.8 mmol/mol [­0.71% points] and ?5.1 mmol/mol [­0.47% points] respectively) for change in HbA1c from baseline (1 RCT, n=1098, 52 weeks).

Dulaglutide 1.5 mg once weekly was non?inferior to liraglutide 1.8 mg once daily (treatment difference ­0.66 mmol/mol [­0.06% points]) for change in HbA1c from baseline (1 RCT, n=599, 26 weeks).

Safety

According to the summary of product characteristics, the most common adverse events (1 in 10 people or more) are hypoglycaemia, particularly in combination with a sulfonylurea or insulin, and gastrointestinal disorders.

According to the European public assessment report (EPAR) possible long?term safety concerns of pancreatitis and pancreatic and thyroid cancers are consistent with other GLP?1 receptor agonists.

Patient factors

Dulaglutide is given once weekly by subcutaneous injection.

The EPAR states that the overall effect of dulaglutide on weight was modest across the AWARD trials (mean changes ­0.87 kg to ­3.03 kg), and that the clinical relevance of the observed effect size with the 1.5 mg dose is uncertain.

According to the summary of product characteristics injection site reactions are uncommon with dulaglutide (more than 1 in a 1000 people to less than 1 in 100).

There are no comparative data with other weekly dose GLP?1 receptor agonists.

G Mohan.