Tirzepatide versus semaglutide 1 mg in type 2 diabetes: SURPASS-2

Why this study matters

SURPASS-2 was the first large trial to test tirzepatide (Zepbound, Mounjaro) directly against semaglutide (Wegovy, Ozempic) in people with type 2 diabetes. Its main purpose was blood sugar control, not weight. Even so, its weight results are often quoted, so it helps to know exactly what was compared and at what dose. The semaglutide dose here was 1 mg, which is a diabetes dose, not the 2.4 mg dose used in weight-management trials.

Who was in the study

The trial randomized 1879 adults with type 2 diabetes. At the start, their average HbA1c was 8.28%, their average age was 56.6 years, and their average weight was 93.7 kg. HbA1c is a blood test that reflects average blood sugar over about three months. The trial lasted 40 weeks.

What the researchers did

This was an open-label, phase 3 trial, meaning participants and researchers knew which medicine each person received. People were randomized, meaning assigned by chance, in equal numbers to four groups: weekly tirzepatide injections at 5 mg, 10 mg or 15 mg, or weekly semaglutide injections at 1 mg.

The primary outcome was the change in HbA1c from the start to week 40. The trial was set up to test whether tirzepatide was at least as good as semaglutide (noninferiority) and then whether it was better (superiority). Weight was a secondary outcome.

What they found

HbA1c fell in every group. The estimated changes were -2.01 percentage points with tirzepatide 5 mg, -2.24 with 10 mg and -2.30 with 15 mg, compared with -1.86 percentage points with semaglutide 1 mg.

A confidence interval, or CI, is the range within which the true difference most likely sits. All three tirzepatide doses met the trial's tests for noninferiority and superiority on HbA1c.

Weight loss was greater with tirzepatide at every dose. The estimated differences from semaglutide 1 mg were -1.9 kg, -3.6 kg and -5.5 kg for the 5, 10 and 15 mg doses (R32-C53). The published summary we reviewed does not report confidence intervals for the weight differences, or the absolute weight change in each group.

Side effects and people who stopped

The most common side effects were stomach and bowel symptoms, mostly mild to moderate, in all groups. Nausea occurred in 17 to 22% of people across the tirzepatide doses and 18% with semaglutide. Diarrhea occurred in 13 to 16% and 12%. Vomiting occurred in 6 to 10% and 8%.

Low blood sugar below 54 mg/dL was reported in 0.6%, 0.2% and 1.7% of the tirzepatide 5, 10 and 15 mg groups, and 0.4% of the semaglutide group. Serious adverse events were reported in 5 to 7% of people on tirzepatide and 3% on semaglutide. The published summary we reviewed does not report how many people in each group stopped treatment, or stopped because of side effects.

What this study does not tell you

• Everyone had type 2 diabetes. The results do not describe people without diabetes.
• The semaglutide comparator was 1 mg, not the 2.4 mg dose used for weight management. This trial cannot be used to compare the two medicines at their weight-management doses. SURMOUNT-5 addresses that question.
• The trial was open-label, so expectations may have influenced how people reported side effects.
• HbA1c was the main outcome. Weight was secondary, the weight differences are reported without confidence intervals, and the trial ran for only 40 weeks.
• This trial's numbers should not be placed next to numbers from unrelated trials to rank medicines.
• We reviewed the abstract only, so the number of countries, sites and other details were not checked.

What it means in Canada

For Canadian readers with type 2 diabetes, SURPASS-2 shows how these two medicines compared on blood sugar and weight at the specific doses tested, over 40 weeks. It does not describe how either medicine is prescribed or paid for here, and it does not compare their weight-management doses. See tirzepatide in Canada, semaglutide in Canada, public drug coverage by province and compare services.

Related reading

Other studies in this library that bear on the same question.

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