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

1879 people with type 2 diabetes, 40 weeks, three tirzepatide doses vs semaglutide 1 mg. Main measure was blood sugar (HbA1c), not weight; tirzepatide won.

2 min readUpdated September 4, 2026By FormBlends editorial team2 sourcesEducational, not medical advice

SURPASS-2: the trial at a glance

From the data
SURPASS-2 at a glance: 1,879 randomised, 40 weeks, primary endpoint HbA1c change.Four facts about SURPASS-2 and its primary result: HbA1c change: -2.01, -2.24 and -2.30 percentage points with tirzepatide 5, 10 and 15 mg versus -1.86 with semaglutide 1 mg. Differences -0.15 (95% CI -0.28 to -0.03; P=0.02), -0.39 (-0.51 to -0.26) and -0.45 (-0.57 to -0.32); P<0.001 for the latter two. Noninferior and superior at all doses.Randomised1,879Duration40 weeksPhase3ComparatoractivecomparatorPrimary resultHbA1c change: -2.01, -2.24 and -2.30 percentage points with tirzepatide 5, 10and 15 mg versus -1.86 with semaglutide 1 mg. Differences -0.15 (95% CI -0.28to -0.03; P=0.02), -0.39 (-0.51 to -0.26) and -0.45 (-0.57 to -0.32); P<0....
Figures as stated in the PubMed abstract. Primary endpoint: Change in HbA1c from baseline to week 40. Source: PubMed 34170647. Source: N Engl J Med 2021;385(6):503-515, PubMed 34170647.

Watch, with the fact-check

Effect of Tirzepatide on Body Weight & Diabetes Control

Mayo Proceedings · 3:44 · uploaded 2025

What it gets right. Two Mayo Clinic research fellows summarise their Mayo Clinic Proceedings paper: in adults with type 1 diabetes and overweight or obesity treated with tirzepatide, mean weight loss of 8.5 percent at a median 8 months and 12 percent at 12 months, a 1 percentage-point A1c fall and a 31.6 percent drop in insulin requirement.

What it leaves out. This is a retrospective observational study of an off-label use; tirzepatide is not approved for type 1 diabetes, and the authors themselves say the finding needs a prospective trial.

Watch on YouTube

Embedded from YouTube (privacy-enhanced player, loads on click); verified against YouTube's oEmbed record on 2026-09-04. Nothing is rehosted. The fact-check is the FormBlends editorial team's reading, not the channel's endorsement.

SURPASS-2 is a diabetes trial, which means its primary endpoint is blood sugar. It is included here because it is the earliest head-to-head between tirzepatide and semaglutide, and because its weight numbers are quoted more often than its HbA1c numbers.

What the trial asked

Whether tirzepatide at 5, 10 or 15 mg is noninferior, and then superior, to semaglutide 1 mg for lowering HbA1c in people with type 2 diabetes.

Design

Phase 3, open-label, randomised 1:1:1:1, 40 weeks. Note the comparator: semaglutide 1 mg, the diabetes dose at the time, not the 2.4 mg weight-management dose used in STEP 1 or the 1.7 to 2.4 mg used in SURMOUNT-5.

Who was enrolled

1879 patients with type 2 diabetes. Baseline mean HbA1c was 8.28 percent, mean age 56.6 years, mean weight 93.7 kg.

Primary endpoint and result

Primary endpoint: change in HbA1c from baseline to week 40.

ArmHbA1c changeDifference vs semaglutide 1 mg (95% CI)
Tirzepatide 5 mg-2.01 points-0.15 (-0.28 to -0.03); P=0.02
Tirzepatide 10 mg-2.24 points-0.39 (-0.51 to -0.26); P less than 0.001
Tirzepatide 15 mg-2.30 points-0.45 (-0.57 to -0.32); P less than 0.001
Semaglutide 1 mg-1.86 points

Tirzepatide was noninferior and superior to semaglutide at every dose.

Key secondary results

Body weight fell more with tirzepatide than with semaglutide: least-squares mean differences of -1.9 kg (5 mg), -3.6 kg (10 mg) and -5.5 kg (15 mg), all P less than 0.001. The abstract gives only the differences, not the absolute change in each arm, so the explorer lists these arms without a bar.

Adverse events and discontinuation

Gastrointestinal events were most common and mainly mild to moderate. Nausea: 17 to 22 percent across tirzepatide doses and 18 percent with semaglutide. Diarrhoea: 13 to 16 percent and 12 percent. Vomiting: 6 to 10 percent and 8 percent. Hypoglycaemia (glucose under 54 mg/dL): 0.6, 0.2 and 1.7 percent on 5, 10 and 15 mg versus 0.4 percent on semaglutide. Serious adverse events: 5 to 7 percent with tirzepatide, 3 percent with semaglutide. The abstract does not give discontinuation percentages.

Funding and registration

Eli Lilly. ClinicalTrials.gov NCT03987919.

What this trial does not show

  • It is not a weight-loss trial. Participants were selected for diabetes, not obesity, and weight was secondary.
  • The semaglutide arm was 1 mg. Any inference about 2.4 mg semaglutide from this trial is an extrapolation.
  • Open-label, 40 weeks, no placebo arm. It cannot say how either drug compares with no treatment.
  • No cardiovascular outcomes. For semaglutide's cardiovascular trial in diabetes, see SUSTAIN-6.

Where the numbers come from

PubMed abstract of the primary paper (PubMed 34170647), fetched 4 September 2026. The weight-management versus diabetes trials guide explains why this trial's design differs from SURMOUNT.

Sources (2)

  1. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2). N Engl J Med 2021;385(6):503-515. PubMed 34170647 Accessed September 4, 2026.
  2. ClinicalTrials.gov NCT03987919 Accessed September 4, 2026.

Canonical URL: https://formblendsresearch.com/trials/surpass-2. Written by the FormBlends editorial team. This page is educational and is not medical advice; see the medical disclaimer.