Ludvik B, Giorgino F, Jodar E, et al. - The results showed that tirzepatide (5, 10, and 15 mg) was superior to titrated insulin degludec, with greater reductions in HbA1c and body weight at week 52 and a lower risk of hypoglycaemia in patients with type 2 diabetes. As per the findings, tirzepatide indicated a similar safety profile to that of GLP-1 receptor agonists.

• Researchers examined 1,947 participants for eligibility, 1,444 of whom were randomly assigned to treatment between April 1 and Nov 15, 2019.In this study, the modified intention-to-treat population was 1,437 participants from the tirzepatide 5 mg (n=358), tirzepatide 10 mg (n=360), tirzepatide 15 mg (n=359), and insulin degludec (n=360) groups.

• From a mean baseline HbA1c of 8·17% (SD 0·91), at week 52, the reductions in HbA1c were 1·93% (SE 0·05) for tirzepatide 5 mg, 2·20% (0·05) for tirzepatide 10 mg, and 2·37% (0·05) for tirzepatide 15 mg, and 1·34% (0·05) for insulin degludec.

• It was shown that the estimated treatment difference (ETD) vs insulin degludec ranged from -0·59% to -1·04% for tirzepatide (p<0·0001 for all tirzepatide doses).

• At week 52, the proportion of participants achieving an HbA1c of less than 7·0% (<53 mmol/mol) was greater (p<0·0001) in all three tirzepatide groups (82%–93%) vs insulin degludec (61%).

• From a baseline of 94·3 kg (SD 20·1), all three tirzepatide doses decreased bodyweight (–7·5 kg to –12·9 kg) at week 52, whereas insulin degludec elevated bodyweight by 2·3 kg.

• The ETD vs insulin degludec ranged from -9·8 kg to –15·2 kg for tirzepatide (p<0·0001 for all tirzepatide doses).

• In tirzepatide-treated participants, the most common adverse events were mild to moderate gastrointestinal events that reduced over time.

• They observed a higher incidence of nausea (12–24%), diarrhoea (15–17%), decreased appetite (6–12%), and vomiting (6–10%) in participants treated with tirzepatide than in those treated with insulin degludec (2%, 4%, 1%, and 1%, respectively).

• They found hypoglycaemia (<54 mg/dL or severe) in five (1%), four (1%), and eight (2%) participants on tirzepatide 5, 10, and 15 mg, respectively, vs 26 (7%) on insulin degludec. It has been reported that treatment discontinuation due to an adverse event was more common in the tirzepatide groups than in the insulin degludec group.

• During the study, five participants died; none of the deaths was considered by the investigators to be related to the study treatment.