Tirzepatide bests insulin degludec for reducing blood sugar and weight in T2DM: Lancet
Spain: Once-weekly subcutaneous injection of tirzepatide (5, 10, and 15 mg) is superior to once-daily subcutaneous injection of titrated insulin degludec in patients with type 2 diabetes, according to a recent study in The Lancet.
The patients administered with tirzepatide showed a greater reduction in blood sugar levels and body weight at week 52 and lower hypoglycemia risk. Also, the safety profile of tirzepatide was found to be similar to that of GLP-1 receptor agonists.
Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist which is under development for the treatment of type 2 diabetes. Ángel Rodríguez, Lilly Spain, Madrid, Spain, and colleagues aimed to assess the efficacy and safety of tirzepatide versus titrated insulin degludec in patients with type 2 diabetes inadequately controlled by metformin with or without SGLT2 inhibitors.
For this purpose, the researchers conducted an open-label, parallel-group, multicentre, multinational, phase 3 study conducted at 122 sites across 13 countries. It included (aged ≥18 years) had a baseline glycated hemoglobin (HbA1c) of 7·0–10·5%, body-mass index of at least 25 kg/m2, stable weight, and were insulin-naive and treated with metformin alone or in combination with an SGLT2 inhibitor for at least 3 months before screening.
People were randomly assigned to receive once-weekly subcutaneous injection of tirzepatide (5, 10, or 15 mg) or once-daily subcutaneous injection of titrated insulin degludec in the ratio of 1:1:1:1. Tirzepatide was initially given at 2·5 mg and the dose was escalated by 2·5 mg every 4 weeks until the assigned dose was reached. Insulin degludec was initially given at 10 U per day and was titrated once weekly to a fasting self-monitored blood glucose of less than 5·0 mmol/L (<90 mg/dL), following a treat-to-target algorithm, for 52 weeks.
The modified intention-to-treat population was 1437 participants from the tirzepatide 5 mg (n=358), tirzepatide 10 mg (n=360), tirzepatide 15 mg (n=359), and insulin degludec (n=360) groups.
Based on the study, the researchers found the following:
- From a mean baseline HbA1c of 8·17%, the reductions in HbA1c at week 52 were 1·93% for tirzepatide 5 mg, 2·20% for tirzepatide 10 mg, and 2·37% for tirzepatide 15 mg, and 1·34% for insulin degludec.
- The non-inferiority margin of 0·3% was met.
- The estimated treatment difference (ETD) versus insulin degludec ranged from –0·59% to –1·04% for tirzepatide.
- The proportion of participants achieving a HbA1c of less than 7·0% (<53 mmol/mol) at week 52 was greater in all three tirzepatide groups (82%–93%) versus insulin degludec (61%).
- At week 52, from a baseline of 94·3 kg, all three tirzepatide doses decreased bodyweight (–7·5 kg to –12·9 kg), whereas insulin degludec increased bodyweight by 2·3 kg.
- The ETD versus insulin degludec ranged from –9·8 kg to –15·2 kg for tirzepatide.
- The most common adverse events in tirzepatide-treated participants were mild to moderate gastrointestinal events that decreased over time. A higher incidence of nausea (12–24%), diarrhoea (15–17%), decreased appetite (6–12%), and vomiting (6–10%) was reported in participants treated with tirzepatide than in those treated with insulin degludec (2%, 4%, 1%, and 1%, respectively).
- Hypoglycaemia (<54 mg/dL or severe) was reported in five (1%), four (1%), and eight (2%) participants on tirzepatide 5, 10, and 15 mg, respectively, versus 26 (7%) on insulin degludec.
- Treatment discontinuation due to an adverse event was more common in the tirzepatide groups than in the insulin degludec group. Five participants died during the study; none of the deaths were considered by the investigators to be related to the study treatment.
"Our findings showed that in type 2 diabetes patients, 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," wrote the authors. "Tirzepatide showed a similar safety profile to that of GLP-1 receptor agonists."
Reference:
The study titled, "Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial," is published in The Lancet.
DOI: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01443-4/fulltext
