Suboptimal therapeutic responses associated with semaglutide in type 2 diabetes and obesity: A meta-analysis of randomized controlled trials

Donghyun Ko; Do Han Kim; Faith Xin Ning Tan; Glenn Jun Kit Ho; Rubhan Chandra; Zhang Zi Xuan; Ethan Tham Kai Jun; Nicole Shu Ying Tang; Hee Seung Yang; Jeffery Wei Heng Koh; Pojsakorn Danpanichkul; Mayank Dalakoti; Nicholas L. Syn; Karn Wijarnpreecha; Hirokazu Takahashi; Ming hua Zheng; Atsushi Nakajima; Mazen Noureddin; Mark Muthiah; Carel W. Le Roux; Mohammad Shadab Siddiqui; Cheng Han Ng

doi:10.1016/j.xcrm.2026.102614

Suboptimal therapeutic responses associated with semaglutide in type 2 diabetes and obesity: A meta-analysis of randomized controlled trials

Donghyun Ko, Do Han Kim, Faith Xin Ning Tan, Glenn Jun Kit Ho, Rubhan Chandra, Zhang Zi Xuan, Ethan Tham Kai Jun, Nicole Shu Ying Tang, Hee Seung Yang, Jeffery Wei Heng Koh, Pojsakorn Danpanichkul, Mayank Dalakoti, Nicholas L. Syn, Karn Wijarnpreecha, Hirokazu Takahashi, Ming hua Zheng, Atsushi Nakajima, Mazen Noureddin, Mark Muthiah, Carel W. Le RouxMohammad Shadab Siddiqui, Cheng Han Ng

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

SummarySemaglutide has emerged as a leading therapy for metabolic disorders, with robust evidence supporting its role in treating obesity and type 2 diabetes while reducing cardiovascular and renal risks. However, limited data exist on the proportion of patients who have suboptimal therapeutic responses or discontinue treatment due to adverse events. We present an analysis including 33 randomized controlled trials (RCTs) comprising 21,023 participants. Across included trials of patients with and without type 2 diabetes, 33.4% and 65.1% of participants did not achieve ≥5% or ≥10% total body weight reduction, respectively. Stratified analyses demonstrated higher rates of suboptimal outcomes among individuals with type 2 diabetes mellitus (T2DM), with up to 79.8% not achieving ≥10% weight loss, compared to 30.1% among individuals without T2DM. While semaglutide is effective in many patients, a substantial subset of patients has suboptimal weight or glycemic improvements or discontinues therapy. This study was registered with PROSPERO (CRD420251086132).

Original language	English (US)
Article number	102614
Pages (from-to)	102614
Journal	Cell Reports Medicine
Volume	7
Issue number	3
DOIs	https://doi.org/10.1016/j.xcrm.2026.102614
State	Published - Mar 17 2026

Keywords

longitudinal
randomized clinical trials
reduction
semaglutide
Weight Loss/drug effects
Diabetes Mellitus, Type 2/drug therapy
Glucagon-Like Peptides/therapeutic use
Humans
Hypoglycemic Agents/therapeutic use
Treatment Outcome
Obesity/drug therapy
Randomized Controlled Trials as Topic

ASJC Scopus subject areas

General Medicine
General Biochemistry, Genetics and Molecular Biology

Divisions

Gastroenterology and Hepatology

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10.1016/j.xcrm.2026.102614

Cite this

Ko, D., Kim, D. H., Tan, F. X. N., Ho, G. J. K., Chandra, R., Xuan, Z. Z., Jun, E. T. K., Tang, N. S. Y., Yang, H. S., Koh, J. W. H., Danpanichkul, P., Dalakoti, M., Syn, N. L., Wijarnpreecha, K., Takahashi, H., Zheng, M. H., Nakajima, A., Noureddin, M., Muthiah, M., ... Ng, C. H. (2026). Suboptimal therapeutic responses associated with semaglutide in type 2 diabetes and obesity: A meta-analysis of randomized controlled trials. Cell Reports Medicine, 7(3), 102614. Article 102614. https://doi.org/10.1016/j.xcrm.2026.102614

Ko, D, Kim, DH, Tan, FXN, Ho, GJK, Chandra, R, Xuan, ZZ, Jun, ETK, Tang, NSY, Yang, HS, Koh, JWH, Danpanichkul, P, Dalakoti, M, Syn, NL, Wijarnpreecha, K, Takahashi, H, Zheng, MH, Nakajima, A, Noureddin, M, Muthiah, M, Le Roux, CW, Siddiqui, MS & Ng, CH 2026, 'Suboptimal therapeutic responses associated with semaglutide in type 2 diabetes and obesity: A meta-analysis of randomized controlled trials', Cell Reports Medicine, vol. 7, no. 3, 102614, pp. 102614. https://doi.org/10.1016/j.xcrm.2026.102614

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title = "Suboptimal therapeutic responses associated with semaglutide in type 2 diabetes and obesity: A meta-analysis of randomized controlled trials",

abstract = "SummarySemaglutide has emerged as a leading therapy for metabolic disorders, with robust evidence supporting its role in treating obesity and type 2 diabetes while reducing cardiovascular and renal risks. However, limited data exist on the proportion of patients who have suboptimal therapeutic responses or discontinue treatment due to adverse events. We present an analysis including 33 randomized controlled trials (RCTs) comprising 21,023 participants. Across included trials of patients with and without type 2 diabetes, 33.4\% and 65.1\% of participants did not achieve ≥5\% or ≥10\% total body weight reduction, respectively. Stratified analyses demonstrated higher rates of suboptimal outcomes among individuals with type 2 diabetes mellitus (T2DM), with up to 79.8\% not achieving ≥10\% weight loss, compared to 30.1\% among individuals without T2DM. While semaglutide is effective in many patients, a substantial subset of patients has suboptimal weight or glycemic improvements or discontinues therapy. This study was registered with PROSPERO (CRD420251086132).",

keywords = "longitudinal, randomized clinical trials, reduction, semaglutide, Weight Loss/drug effects, Diabetes Mellitus, Type 2/drug therapy, Glucagon-Like Peptides/therapeutic use, Humans, Hypoglycemic Agents/therapeutic use, Treatment Outcome, Obesity/drug therapy, Randomized Controlled Trials as Topic",

author = "Donghyun Ko and Kim, \{Do Han\} and Tan, \{Faith Xin Ning\} and Ho, \{Glenn Jun Kit\} and Rubhan Chandra and Xuan, \{Zhang Zi\} and Jun, \{Ethan Tham Kai\} and Tang, \{Nicole Shu Ying\} and Yang, \{Hee Seung\} and Koh, \{Jeffery Wei Heng\} and Pojsakorn Danpanichkul and Mayank Dalakoti and Syn, \{Nicholas L.\} and Karn Wijarnpreecha and Hirokazu Takahashi and Zheng, \{Ming hua\} and Atsushi Nakajima and Mazen Noureddin and Mark Muthiah and \{Le Roux\}, \{Carel W.\} and Siddiqui, \{Mohammad Shadab\} and Ng, \{Cheng Han\}",

note = "Copyright {\textcopyright} 2026. Published by Elsevier Inc.",

year = "2026",

month = mar,

day = "17",

doi = "10.1016/j.xcrm.2026.102614",

language = "English (US)",

volume = "7",

pages = "102614",

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T1 - Suboptimal therapeutic responses associated with semaglutide in type 2 diabetes and obesity

T2 - A meta-analysis of randomized controlled trials

AU - Ko, Donghyun

AU - Kim, Do Han

AU - Tan, Faith Xin Ning

AU - Ho, Glenn Jun Kit

AU - Chandra, Rubhan

AU - Xuan, Zhang Zi

AU - Jun, Ethan Tham Kai

AU - Tang, Nicole Shu Ying

AU - Yang, Hee Seung

AU - Koh, Jeffery Wei Heng

AU - Danpanichkul, Pojsakorn

AU - Dalakoti, Mayank

AU - Syn, Nicholas L.

AU - Wijarnpreecha, Karn

AU - Takahashi, Hirokazu

AU - Zheng, Ming hua

AU - Nakajima, Atsushi

AU - Noureddin, Mazen

AU - Muthiah, Mark

AU - Le Roux, Carel W.

AU - Siddiqui, Mohammad Shadab

AU - Ng, Cheng Han

PY - 2026/3/17

Y1 - 2026/3/17

N2 - SummarySemaglutide has emerged as a leading therapy for metabolic disorders, with robust evidence supporting its role in treating obesity and type 2 diabetes while reducing cardiovascular and renal risks. However, limited data exist on the proportion of patients who have suboptimal therapeutic responses or discontinue treatment due to adverse events. We present an analysis including 33 randomized controlled trials (RCTs) comprising 21,023 participants. Across included trials of patients with and without type 2 diabetes, 33.4% and 65.1% of participants did not achieve ≥5% or ≥10% total body weight reduction, respectively. Stratified analyses demonstrated higher rates of suboptimal outcomes among individuals with type 2 diabetes mellitus (T2DM), with up to 79.8% not achieving ≥10% weight loss, compared to 30.1% among individuals without T2DM. While semaglutide is effective in many patients, a substantial subset of patients has suboptimal weight or glycemic improvements or discontinues therapy. This study was registered with PROSPERO (CRD420251086132).

AB - SummarySemaglutide has emerged as a leading therapy for metabolic disorders, with robust evidence supporting its role in treating obesity and type 2 diabetes while reducing cardiovascular and renal risks. However, limited data exist on the proportion of patients who have suboptimal therapeutic responses or discontinue treatment due to adverse events. We present an analysis including 33 randomized controlled trials (RCTs) comprising 21,023 participants. Across included trials of patients with and without type 2 diabetes, 33.4% and 65.1% of participants did not achieve ≥5% or ≥10% total body weight reduction, respectively. Stratified analyses demonstrated higher rates of suboptimal outcomes among individuals with type 2 diabetes mellitus (T2DM), with up to 79.8% not achieving ≥10% weight loss, compared to 30.1% among individuals without T2DM. While semaglutide is effective in many patients, a substantial subset of patients has suboptimal weight or glycemic improvements or discontinues therapy. This study was registered with PROSPERO (CRD420251086132).

KW - longitudinal

KW - randomized clinical trials

KW - reduction

KW - semaglutide

KW - Weight Loss/drug effects

KW - Diabetes Mellitus, Type 2/drug therapy

KW - Glucagon-Like Peptides/therapeutic use

KW - Humans

KW - Hypoglycemic Agents/therapeutic use

KW - Treatment Outcome

KW - Obesity/drug therapy

KW - Randomized Controlled Trials as Topic

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SN - 2666-3791

VL - 7

SP - 102614

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 3

M1 - 102614

ER -

Suboptimal therapeutic responses associated with semaglutide in type 2 diabetes and obesity: A meta-analysis of randomized controlled trials

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