Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial

Rosenstock, Julio; Wysham, Carol; Frías, Juan P.; Kaneko, Shuji; Lee, Clare J.; Landó, Laura Fernández; Mao, Huzhang; Cui, Xuewei; Karanikas, Chrisanthi A.; Thieu, Vivian T.

doi:10.1016/s0140-6736(21)01324-6

Cited by 599 publications

(860 citation statements)

References 19 publications

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“…Overall, the highest dose of tirzepatide had superior effects on HbA1c reduction, and the change in the HbA1c presumably occurred as early as 12 weeks, with no differences noted at week 26 or 40. The most recent phase 3 trial (SURPASS-1) has indeed demonstrated a similar reduction in HbA1c, FSG, and body weight in patients with T2DM treated with tirzepatide (5,10, and 15 mg) as monotherapy [17]. Ongoing RCTs [24][25][26][27][28][29] will confirm whether similar benefits could be expected in an overweight or obese population with (SURMOUNT-2) [29] or without T2DM (SURMOUNT-3, SURMOUNT-4) [25,26] and in patients with T2DM inadequately controlled on insulin glargine with/without metformin (SURPASS-6) [27].…”

Section: Discussionmentioning

confidence: 87%

“…Tirzepatide is a novel therapeutic agent administered once a week as a dual GLP-1/GIP receptor, formulated as a 39-amino acid synthetic peptide, based on the native GIP sequence [9]. In individual RCTs, tirzepatide alone or added to metformin was shown to improve glycemic control with weight loss compared with a placebo or selective GLP-1 receptor agonists (dulaglutide or semaglutide) [17][18][19][20]. However, to date, no systematic compilation of the available evidence of tirzepatide has been performed.…”

Section: Discussionmentioning

confidence: 99%

“…From 242 identified records, we excluded nonhuman and irrelevant studies, leaving 16 reports for full-text assessment. After further selection (Figure 1), four unique RCTs fulfilled the inclusion criteria (Table 1) [17][18][19][20]. RCTs published between 2018 and 2021 included 2783 (range: 26-1490) participants with T2DM; three out of four studies were multinational RCTs.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…All included studies exhibit a low risk of selection bias, performance bias, detection bias, and reporting bias. The risk of bias in allocation concealment was generally unclear apart from the Rosenstock et al [17] study. One study [20] has a high risk of bias because it did not provide details of blinding the participants and their outcome assessment.…”

Section: Study Characteristicsmentioning

confidence: 99%

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Efficacy and Safety of Tirzepatide in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Phase II/III Trials

2021

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Tirzepatide is a novel once-a-week dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, currently under trial to assess glycemic efficacy and safety in people with type 2 diabetes. A systematic review and meta-analysis were conducted to investigate the efficacy of tirzepatide on glycated hemoglobin (HbA1c, %), fasting serum glucose (mg/dL), and body weight (kg) in patients with uncontrolled type 2 diabetes (HbA1c > 7.0%). Mean changes for efficacy and proportions (safety) with corresponding 95% confidence intervals (CIs) were used to provide pooled estimates. A total of four randomized controlled trials, comprising 2783 patients of whom 69.4% (n = 1934) were treated with 5 mg (n = 646), 10 mg (n = 641), or 15 mg (n = 647) of tirzepatide, were compared to the placebo (n = 192) or the selective GLP-1 receptor agonist (n = 523). The pooled analysis showed that tirzepatide treatment resulted in a greater lowering of the HbA1c (–1.94%, 95% CI: –2.02 to –1.87), fasting serum glucose (–54.72 mg/dL, 95% CI: –62.05 to –47.39), and body weight (–8.47, 95% CI: –9.66 to –7.27). We also found that improvement in the HbA1c levels was still maintained at weeks 26 and 40 from the long-term trials. As for safety, only 3% experienced hypoglycemia, and 4% (95% CI: 2 to 6) experienced serious adverse events, while the discontinuation of therapy percentage was 7% (95% CI: 5 to 8). Tirzepatide significantly improved glycemic control and body weight and had an acceptable safety profile, indicating that it is an effective therapeutic option for glucose-lowering in patients with type 2 diabetes mellitus.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Study Characteristicsmentioning

confidence: 99%

Section: Study Characteristicsmentioning

confidence: 99%

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Efficacy and Safety of Tirzepatide in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Phase II/III Trials

2021

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“…Die Mehrzahl der Teilnehmer erreichte einen HbA1c-Wert von unter 7 % (87 % in der 5 mg-Dosierung, 92 % in der 10 mg-Dosierung und 88 % in der 15 mg-Dosierung gegenüber 20 % in der Plazebogruppe). Parallel zur Blutzuckersenkung konnte eine Gewichtsreduktion um 7,9 % (5 mg), 9,3 % (10 mg) und 11,0 % (15 mg) erreicht werden, was in der höchsten Dosierung einer Gewichtsreduktion von 9,5 kg (-0,7 kg unter Plazebo) bei einem Ausgangsgewicht von 85,9 kg (BMI 31,9 kg/m 2 ) entspricht [25]. Gastrointestinale Nebenwirkungen, die v. a. zu Behandlungsbeginn auftraten, sollen sich, bei erhaltener Wirksamkeit, durch Dosis Eskalationen reduzieren lassen.…”

Section: Inkretin-koagonistenunclassified

Adipositas und Diabetes

Aberle

Lautenbach

Meyhöfer

et al. 2021

Diabetologie und Stoffwechsel

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Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes

Dahl

Onishi

Norwood³

et al. 2022

JAMA

318

437

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The effects of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, as an addition to insulin glargine for treatment of type 2 diabetes have not been described. OBJECTIVE To assess the efficacy and safety of tirzepatide added to insulin glargine in patients with type 2 diabetes with inadequate glycemic control.DESIGN, SETTING, AND PARTICIPANTS Randomized phase 3 clinical trial conducted at 45 medical research centers and hospitals in 8 countries (enrollment from August 30, 2019, to March 20, 2020 follow-up completed January 13, 2021) in 475 adults with type 2 diabetes and inadequate glycemic control while treated with once-daily insulin glargine with or without metformin.INTERVENTIONS Patients were randomized in a 1:1:1:1 ratio to receive once-weekly subcutaneous injections of 5-mg (n = 116), 10-mg (n = 119), or 15-mg (n = 120) tirzepatide or volume-matched placebo (n = 120) over 40 weeks. Tirzepatide was initiated at 2.5 mg/week and escalated by 2.5 mg every 4 weeks until the assigned dose was achieved. MAIN OUTCOMES AND MEASURESThe primary end point was mean change from baseline in glycated hemoglobin A 1c (HbA 1c ) at week 40. The 5 key secondary end points included mean change in body weight and percentage of patients achieving prespecified HbA 1c levels. RESULTS Among 475 randomized participants (211 [44%] women; mean [SD] age, 60.6 [9.9] years; mean [SD] HbA 1c , 8.31% [0.85%]), 451 (94.9%) completed the trial. Treatment was prematurely discontinued by 10% of participants in the 5-mg tirzepatide group, 12% in the 10-mg tirzepatide group, 18% in the 15-mg tirzepatide group, and 3% in the placebo group. At week 40, mean HbA 1c change from baseline was −2.40% with 10-mg tirzepatide and −2.34% with 15-mg tirzepatide vs −0.86% with placebo (10 mg: difference vs placebo, −1.53% [97.5% CI, −1.80% to −1.27%]; 15 mg: difference vs placebo, −1.47% [97.5% CI, −1.75% to −1.20%]; P < .001 for both). Mean HbA 1c change from baseline was −2.11% with 5-mg tirzepatide (difference vs placebo, −1.24% [95% CI, −1.48% to −1.01%]; P < .001]). Mean body weight change from baseline was −5.4 kg with 5-mg tirzepatide, −7.5 kg with 10-mg tirzepatide, −8.8 kg with 15-mg tirzepatide and 1.6 kg with placebo (5 mg: difference, −7.1 kg [95% CI, −8.7 to −5.4]; 10 mg: difference, −9.1 kg [95% CI, −10.7 to −7.5]; 15 mg: difference, −10.5 kg [95% CI, −12.1 to −8.8]; P < .001 for all). Higher percentages of patients treated with tirzepatide vs those treated with placebo had HbA 1c less than 7% (85%-90% vs 34%; P < .001 for all). The most common treatment-emergent adverse events in the tirzepatide groups vs placebo group were diarrhea (12%-21% vs 10%) and nausea (13%-18% vs 3%).CONCLUSIONS AND RELEVANCE Among patients with type 2 diabetes and inadequate glycemic control despite treatment with insulin glargine, the addition of subcutaneous tirzepatide, compared with placebo, to titrated insulin glargine resulted in statistically significant improvements in glycemic control after 40 weeks.

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Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial

Cited by 599 publications

References 19 publications

Efficacy and Safety of Tirzepatide in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Phase II/III Trials

Efficacy and Safety of Tirzepatide in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Phase II/III Trials

Adipositas und Diabetes

Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes

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