Table 1.

Summary of the SURPASS program, phase III clinical trials (34–37).

Study(year)	Study duration(weeks)	Intervention vs. comparator	Randomization(number of participants)	Baseline characteristics	Main findings
SURPASS-1 Rosenstock J (2021)	40	Tirzepatide vs. placebo (monotherapy in naïve T2D patients)	1:1:1:1 Tirzepatide 5 mg qw (125) Tirzepatide 10 mg qw (125) Tirzepatide 15 mg qw (125) Placebo qw (121)	-HbA1c 7.9% -54y -women 48% -mean diabetes evolution 4.7y -BMI 31.9 Kg/m2	HbA1c -1.87% Tirzepatide 5 mg -1.89% Tirzepatide 10 mg -2.07% Tirzepatide 15 mg +0.04 placebo -HbA1c <7% 87-92% (Tirzepatide) vs. 20% (placebo) -HbA1c ≤6.5% 81-86% (Tirzepatide) vs. 10% (placebo) - HbA1c <5.7% 31-52% (Tirzepatide) vs. 1% (placebo) Weight loss -7 to -9.5 kg (Tirzepatide 5 to 15 mg)
SURPASS-2 Frías JP (2021)	40	Tirzepatide vs. Semaglutide (T2D patients with poor glycemic control while on metformin)	1:1:1:1 Tirzepatide 5 mg qw (470) Tirzepatide 10 mg qw (469) Tirzepatide 15 mg qw (470) Semaglutide 1 mg qw (469)	-HbA1c 8.28% -56.6y -women 53% -mean diabetes evolution 8.6y -BMI 31.9 kg/m2 -waist 109.3 cm -eGFR 96 ml/min	HbA1c -2.01% Tirzepatide 5 mg -2.24% Tirzepatide 10 mg -2.3% Tirzepatide 15 mg -1.86% Semaglutide 1mg -HbA1c <7% 82-86% (Tirzepatide) vs. 79% (Semaglutide) -HbA1c ≤6.5% 69-80% (Tirzepatide) vs. 64% (Semaglutide) - HbA1c <5.7% 27-46% (Tirzepatide) vs. 19% (Semaglutide) Weight loss -7.6 to -11.2 Kg (Tirzepatide 5-15 mg) vs. -5.7 Kg (Semaglutide 1 mg)
SUPRASS-3 Ludvik B (2021)	52	Tirzepatide vs. insulin Degludec (as an add-on to metformin +/- sodium glucose transporter 2 inhibitors)	1:1:1:1 Tirzepatide 5 mg qw (361) Tirzepatide 10 mg qw (361) Tirzepatide 15 mg qw (361) titrated insulin Degludec (361)	-HbA1c 8.17% -18y -diabetes duration 8.4y -BMI >25 kg/m2	HbA1c -1.9% Tirzepatide 5 mg, qw -2.2% Tirzepatide 10 mg, qw -2.37% Tirzepatide 15 mg, qw -1.34 titrated insulin Degludec -HbA1c <7% 82-93% (Tirzepatide) vs. 61% (titrated insulin Degludec) Weight loss -7.5 to -11.2 Kg (Tirzepatide 5-15 mg) vs. +2.3 Kg (titrated insulin Degludec)
SURPASS-4 Del Prato S (2021)	52	Tirzepatide vs. Insulin Glargine (as an add-on to metformin +/- secretagogues +/- sodium glucose transporter 2 inhibitors in any combinations in patients at high cardiovascular risk)	1:1:1:3 Tirzepatide 5 mg qw (329) Tirzepatide 10 mg qw (328) Tirzepatide 15 mg qw (338) titrated insulin Glargine (1000)	-HbA1c 8.5% ->18y -diabetes evolution 11.8y -BMI >25 kg/m2	HbA1c -2.43% Tirzepatide 10 mg, qw -2.28% Tirzepatide 15 mg, qw -1.44% titrated insulin Glargine MACE-4 events (cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina): Tirzepatide compared to insulin Glargine hazard ratio 0.74 (95% CI 0.51–1.08).