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Randomized controlled trial

SURPASS-2: tirzepatide (Mounjaro) vs semaglutide in diabetes

HbA1c fell by 2.01, 2.24 and 2.30 percentage points with tirzepatide 5, 10 and 15 mg, compared with 1.86 points with semaglutide 1 mg; the differences were −0.15 (95% CI, −0.28 to −0.03), −0.39 (95% CI, −0.51 to −0.26) and −0.45 points (95% CI, −0.57 to −0.32).

Frías JP et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. New England Journal of Medicine, 2021. DOI: 10.1056/NEJMoa2107519

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Key facts

Drugs
tirzepatide and semaglutide
Design
Randomized controlled trial
Participants
1,879
Duration
40 weeks
Funding
Eli Lilly
Registry
NCT03987919
Population
1,879 adults with type 2 diabetes not controlled on metformin.
Primary outcome
Change in HbA1c at 40 weeks with tirzepatide 5, 10 or 15 mg versus semaglutide 1 mg (noninferiority and superiority).

What it found

HbA1c fell by 2.01, 2.24 and 2.30 percentage points with tirzepatide 5, 10 and 15 mg, compared with 1.86 points with semaglutide 1 mg; the differences were −0.15 (95% CI, −0.28 to −0.03), −0.39 (95% CI, −0.51 to −0.26) and −0.45 points (95% CI, −0.57 to −0.32). Tirzepatide was noninferior and superior to semaglutide at every dose. Weight loss was greater with tirzepatide: differences of −1.9, −3.6 and −5.5 kg versus semaglutide. Digestive adverse effects were similar across groups (nausea in 17 to 22% on tirzepatide and 18% on semaglutide).

Limitations

Funded by Eli Lilly. It compared tirzepatide with semaglutide 1 mg, not with the 2 mg dose later approved for diabetes or the 2.4 mg dose for obesity. Open-label with respect to the injection device, although HbA1c was assessed blinded.

What it means for you

In type 2 diabetes, tirzepatide (Mounjaro) lowered HbA1c and weight somewhat more than semaglutide 1 mg. Semaglutide was used at a lower dose than the one later approved for diabetes. Choosing a diabetes treatment depends on many factors your doctor weighs.

Further reading

Related trials

  • tirzepatide52 weeks

    SURPASS-3

    At 52 weeks, HbA1c fell by 1.93, 2.20 and 2.37 percentage points with tirzepatide 5, 10 and 15 mg, and by 1.34 points with insulin degludec.

  • tirzepatide and dulaglutideEvent-driven

    SURPASS-CVOT

    Over a median follow-up of 4.0 years, a major cardiovascular event occurred in 12.2% of patients on tirzepatide and 13.1% on dulaglutide.

  • tirzepatide72 weeks

    SURMOUNT-2

    In people with type 2 diabetes and obesity, tirzepatide reduced weight by 12.8% with 10 mg and 14.7% with 15 mg at 72 weeks, compared with 3.2% on placebo.

  • tirzepatide88 weeks

    SURMOUNT-4 (post hoc analysis)

    After switching from tirzepatide to placebo, the more weight people regained between week 36 and week 88, the more their cardiometabolic parameters worsened: waist circumference increased by 0.8 cm in those who regained less than 25% of the weight lost and by 14.7 cm in those who regained 75% or more.

Sources

The original paper and the records consulted for this summary, with the date they were accessed.

  1. New England Journal of Medicine.Frías JP, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021;385(6):503-515.accessed .
  2. National Library of Medicine (PubMed).PubMed record PMID 34170647 (abstract).accessed .