DiabetologiaType 2 DiabetesDecember 19, 2025

Efficacy of tirzepatide versus semaglutide in achieving therapeutic targets in type 2 diabetes: a post hoc analysis of the SURPASS-2 Trial.

Neves JS, Leite AR, Vale C, Marques P, Vasques-Nóvoa F, Leite-Moreira A, Ferreira JP

View on PubMed DOI: 10.1007/s00125-025-06637-7

Key Finding

Tirzepatide helped 57% of people with type 2 diabetes hit 3 or more key health targets compared to just 34% with semaglutide - like having a more precise tool that hits multiple bullseyes at once.

What This Study Found

Think of managing type 2 diabetes like juggling four balls at once: blood sugar (HbA1c), blood pressure, cholesterol, and weight. Most people drop some balls - at the start of this study, only 21% were successfully keeping 2 or more balls in the air for standard targets. This head-to-head comparison of 1,879 people tested whether tirzepatide (the newer dual-hormone drug) could help people juggle better than semaglutide (the established single-hormone drug). The results were striking: tirzepatide acted like having stickier hands. For standard health targets, 57% of people on the highest tirzepatide dose managed 3 or more goals versus 34% on semaglutide. For the more challenging intensive targets (like aiming for even tighter blood sugar and losing 15% body weight), tirzepatide was even more impressive - 29% hit 3 or more targets compared to just 8% with semaglutide. The drug was particularly powerful for weight loss, nearly quadrupling the odds of losing 15% of body weight.

Statistics Decoded

OR 1.88 for intensive blood sugar control means tirzepatide users were 88% more likely to hit the tighter HbA1c target - like going from a 1-in-10 chance to nearly 1-in-5. The weight loss odds ratios are even more dramatic: OR 3.86 for 15% weight loss means tirzepatide users were nearly 4 times more likely to achieve this major weight milestone. The 95% confidence intervals (like [2.69, 5.55]) tell us we're pretty confident the real benefit is somewhere between 2.7 and 5.6 times better - this wasn't just lucky. Starting from a low baseline where 58% of people achieved zero intensive targets, tirzepatide's ability to get 29% to three or more targets represents a massive improvement in comprehensive diabetes care.

Why This Matters

This matters because diabetes complications come from multiple risk factors working together - having one piece of the puzzle isn't enough. Tirzepatide's ability to simultaneously tackle blood sugar, weight, and blood pressure in the same person could translate to fewer heart attacks, strokes, and other serious complications down the road.

Original Abstract

Simultaneous control of HbA1c, lipid profile, BP and body weight is essential for preventing chronic complications of type 2 diabetes. Glucagon-like peptide-1 (GLP-1)-based therapies improve all these variables but whether the dual GLP-1 / glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide is superior to semaglutide in attaining therapeutic targets remains unclear. We performed a post hoc analysis of the SURPASS-2 trial, a randomised phase 3 study including 1879 adults with type 2 diabetes. Participants were randomised to receive tirzepatide (5, 10 or 15 mg) or semaglutide (1 mg). In this analysis, we compared the effects of tirzepatide vs semaglutide on the attainment of standard (HbA1c <53 mmol/mol [7%], BP <140/90 mmHg, LDL-cholesterol <1.8 mmol/l, >10% weight loss) and intensive (HbA1c <48 mmol/mol [6.5%], BP <130/80 mmHg, LDL-cholesterol <1.4 mmol/l , >15% weight loss) therapeutic targets at 40 weeks. In the SURPASS-2 trial, at baseline, 19% of participants were on target for attaining no standard goals, 59% for one goal and 21% for two or more goals. For intensive therapeutic targets, 58% of participants were on target for attaining zero goals, 38% for one goal and 4% for two goals. All doses of tirzepatide increased the number of achieved standard and intensive targets compared with semaglutide. For standard targets, 34% of participants treated with semaglutide met three or more targets, compared with 42%, 53% and 57% with tirzepatide 5, 10 and 15 mg, respectively. For intensive targets, 8% of participants treated with semaglutide met three or more targets, vs 15%, 20% and 29% with tirzepatide. Regarding specific therapeutic goals, tirzepatide increased the odds of achieving standard and intensive targets for HbA1c (HbA1c <53 mmol/mol [7%], OR 1.50 [95% CI 1.12, 2.00]; HbA1c <48 mmol/mol [6.5%], OR 1.88 [95%CI 1.49, 2.36]) and weight loss (weight loss >10%, OR 2.72 [95% CI 2.14, 3.47]; weight loss >15%, OR 3.86 [95% CI 2.69, 5.55]) and the intensive target for BP (OR 1.45 [95% CI 1.17, 1.81]). Tirzepatide improves therapeutic target attainment compared with semaglutide in type 2 diabetes. Longer trials are needed to confirm benefits on long-term prognosis. Data for this post hoc analysis was accessed through the Vivli (Center for Global Clinical Research Data) platform ( https://vivli.org ) with the Vivli ID 00009964.