TY - JOUR
T1 - Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2)
T2 - a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial
AU - SURMOUNT-2 investigators
AU - Garvey, W. Timothy
AU - Frias, Juan P.
AU - Jastreboff, Ania M.
AU - le Roux, Carel W.
AU - Sattar, Naveed
AU - Aizenberg, Diego
AU - Mao, Huzhang
AU - Zhang, Shuyu
AU - Ahmad, Nadia N.
AU - Bunck, Mathijs C.
AU - Benabbad, Imane
AU - Zhang, Xiaotian M.
AU - Abalos, Franklin H.
AU - Manghi, Federico C.P.
AU - Zaidman, Cesar J.
AU - Vico, Marisa L.
AU - Costanzo, Pablo R.
AU - Serra, Leonardo P.
AU - MacKinnon, Ignacio J.
AU - Hissa, Miguel N.
AU - Vidotti, Maria H.
AU - Kerr Saraiva, Jose F.
AU - Alves, Breno B.
AU - Franco, Denise R.
AU - Moratto, Otavio
AU - Murthy, Sreenivasa
AU - Goyal, Ghanshyam
AU - Yamasaki, Yoshimitsu
AU - Sato, Nobuyuki
AU - Inoue, Satoshi
AU - Asakura, Taro
AU - Shestakova, Marina
AU - Khaykina, Elena
AU - Troshina, Ekaterina
AU - Vorokhobina, Natalia
AU - Ametov, Alexander
AU - Tu, Shih Te
AU - Yang, Chwen Yi
AU - Lee, I. Te
AU - Huang, Chien Ning
AU - Ou, Horng Yih
AU - Freeman, George
AU - Machineni, Sriram
AU - Klein, Klara
AU - Sultan, Senan
AU - Parsa, Alan
AU - Otero-Martinez, Juan
AU - Gonzalez, Alex
AU - Bhargava, Anuj
AU - Brian, Susan
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/8/19
Y1 - 2023/8/19
N2 - Background: Weight reduction is essential for improving health outcomes in people with obesity and type 2 diabetes. We assessed the efficacy and safety of tirzepatide, a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, versus placebo, for weight management in people living with obesity and type 2 diabetes. Methods: This phase 3, double-blind, randomised, placebo-controlled trial was conducted in seven countries. Adults (aged ≥18 years) with a body-mass index (BMI) of 27 kg/m2 or higher and glycated haemoglobin (HbA1c) of 7–10% (53–86 mmol/mol) were randomly assigned (1:1:1), using a computer-generated random sequence via a validated interactive web-response system, to receive either once-weekly, subcutaneous tirzepatide (10 mg or 15 mg) or placebo for 72 weeks. All participants, investigators, and the sponsor were masked to treatment assignment. Coprimary endpoints were the percent change in bodyweight from baseline and bodyweight reduction of 5% or higher. The treatment-regimen estimand assessed effects regardless of treatment discontinuation or initiation of antihyperglycaemic rescue therapy. Efficacy and safety endpoints were analysed with data from all randomly assigned participants (intention-to-treat population). This trial is registered with ClinicalTrials.gov, NCT04657003. Findings: Between March 29, 2021, and April 10, 2023, of 1514 adults assessed for eligibility, 938 (mean age 54·2 years [SD 10·6], 476 [51%] were female, 710 [76%] were White, and 561 [60%] were Hispanic or Latino) were randomly assigned and received at least one dose of tirzepatide 10 mg (n=312), tirzepatide 15 mg (n=311), or placebo (n=315). Baseline mean bodyweight was 100·7 kg (SD 21·1), BMI 36·1 kg/m2 (SD 6·6), and HbA1c 8·02% (SD 0·89; 64·1 mmol/mol [SD 9·7]). Least-squares mean change in bodyweight at week 72 with tirzepatide 10 mg and 15 mg was –12·8% (SE 0·6) and –14·7% (0·5), respectively, and –3·2% (0·5) with placebo, resulting in estimated treatment differences versus placebo of –9·6% percentage points (95% CI –11·1 to –8·1) with tirzepatide 10 mg and –11·6% percentage points (–13·0 to –10·1) with tirzepatide 15 mg (all p<0·0001). More participants treated with tirzepatide versus placebo met bodyweight reduction thresholds of 5% or higher (79–83% vs 32%). The most frequent adverse events with tirzepatide were gastrointestinal-related, including nausea, diarrhoea, and vomiting and were mostly mild to moderate in severity, with few events leading to treatment discontinuation (<5%). Serious adverse events were reported by 68 (7%) participants overall and two deaths occurred in the tirzepatide 10 mg group, but deaths were not considered to be related to the study treatment by the investigator. Interpretation: In this 72-week trial in adults living with obesity and type 2 diabetes, once-weekly tirzepatide 10 mg and 15 mg provided substantial and clinically meaningful reduction in bodyweight, with a safety profile that was similar to other incretin-based therapies for weight management. Funding: Eli Lilly and Company.
AB - Background: Weight reduction is essential for improving health outcomes in people with obesity and type 2 diabetes. We assessed the efficacy and safety of tirzepatide, a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, versus placebo, for weight management in people living with obesity and type 2 diabetes. Methods: This phase 3, double-blind, randomised, placebo-controlled trial was conducted in seven countries. Adults (aged ≥18 years) with a body-mass index (BMI) of 27 kg/m2 or higher and glycated haemoglobin (HbA1c) of 7–10% (53–86 mmol/mol) were randomly assigned (1:1:1), using a computer-generated random sequence via a validated interactive web-response system, to receive either once-weekly, subcutaneous tirzepatide (10 mg or 15 mg) or placebo for 72 weeks. All participants, investigators, and the sponsor were masked to treatment assignment. Coprimary endpoints were the percent change in bodyweight from baseline and bodyweight reduction of 5% or higher. The treatment-regimen estimand assessed effects regardless of treatment discontinuation or initiation of antihyperglycaemic rescue therapy. Efficacy and safety endpoints were analysed with data from all randomly assigned participants (intention-to-treat population). This trial is registered with ClinicalTrials.gov, NCT04657003. Findings: Between March 29, 2021, and April 10, 2023, of 1514 adults assessed for eligibility, 938 (mean age 54·2 years [SD 10·6], 476 [51%] were female, 710 [76%] were White, and 561 [60%] were Hispanic or Latino) were randomly assigned and received at least one dose of tirzepatide 10 mg (n=312), tirzepatide 15 mg (n=311), or placebo (n=315). Baseline mean bodyweight was 100·7 kg (SD 21·1), BMI 36·1 kg/m2 (SD 6·6), and HbA1c 8·02% (SD 0·89; 64·1 mmol/mol [SD 9·7]). Least-squares mean change in bodyweight at week 72 with tirzepatide 10 mg and 15 mg was –12·8% (SE 0·6) and –14·7% (0·5), respectively, and –3·2% (0·5) with placebo, resulting in estimated treatment differences versus placebo of –9·6% percentage points (95% CI –11·1 to –8·1) with tirzepatide 10 mg and –11·6% percentage points (–13·0 to –10·1) with tirzepatide 15 mg (all p<0·0001). More participants treated with tirzepatide versus placebo met bodyweight reduction thresholds of 5% or higher (79–83% vs 32%). The most frequent adverse events with tirzepatide were gastrointestinal-related, including nausea, diarrhoea, and vomiting and were mostly mild to moderate in severity, with few events leading to treatment discontinuation (<5%). Serious adverse events were reported by 68 (7%) participants overall and two deaths occurred in the tirzepatide 10 mg group, but deaths were not considered to be related to the study treatment by the investigator. Interpretation: In this 72-week trial in adults living with obesity and type 2 diabetes, once-weekly tirzepatide 10 mg and 15 mg provided substantial and clinically meaningful reduction in bodyweight, with a safety profile that was similar to other incretin-based therapies for weight management. Funding: Eli Lilly and Company.
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U2 - 10.1016/S0140-6736(23)01200-X
DO - 10.1016/S0140-6736(23)01200-X
M3 - Article
C2 - 37385275
AN - SCOPUS:85163477408
SN - 0140-6736
VL - 402
SP - 613
EP - 626
JO - The Lancet
JF - The Lancet
IS - 10402
ER -