PMID- 37853960
OWN - NLM
STAT- MEDLINE
DCOM- 20240122
LR  - 20240122
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 26
IP  - 2
DP  - 2024 Feb
TI  - Gastrointestinal adverse events and weight reduction in people with type 2 
      diabetes treated with tirzepatide in the SURPASS clinical trials.
PG  - 473-481
LID - 10.1111/dom.15333 [doi]
AB  - AIMS: To evaluate gastrointestinal adverse events (AEs) and the impact of nausea, 
      vomiting or diarrhoea (N/V/D) and any gastrointestinal (GI) AEs overall on weight 
      change with tirzepatide across the SURPASS-1 to -5 clinical trials. MATERIALS AND 
      METHODS: Participants with type 2 diabetes were randomized to receive once-weekly 
      tirzepatide (5, 10 or 15 mg) or comparator (placebo, semaglutide 1 mg once 
      weekly, or titrated daily basal insulins) as monotherapy or added on to 
      background antihyperglycaemic medication(s). This post hoc analysis subdivided 
      participants within each trial into subgroups that self-reported (yes/no) any 
      N/V/D or GI AEs. Change from baseline in body weight at the primary timepoint was 
      assessed within each trial and subgroup. Mediation analyses were conducted to 
      evaluate the contribution of direct and indirect (mediated by N/V/D or GI AEs) 
      effects of tirzepatide on weight change versus comparators. RESULTS: Across the 
      SURPASS-1 to -5 trials (N = 6263), nausea (12%-24%), diarrhoea (12%-22%), and 
      vomiting (2%-13%) were the most common GI AEs reported with tirzepatide; these 
      were transient and of mild-to-moderate severity. Mean weight reduction at the 
      primary timepoint with tirzepatide was consistent between participants who 
      reported N/V/D (-6.2 to -14.9 kg) and those who did not report N/V/D (-6.2 to 
      -13.3 kg). Mean weight reduction was significantly (P < 0.01) greater with 
      tirzepatide compared with placebo, semaglutide 1 mg, and basal insulins within 
      the N/V/D and GI AEs subgroups. Mediation analyses suggested minimal contribution 
      (<6%) of N/V/D and GI AEs to the overall difference in weight change between 
      tirzepatide and comparators. CONCLUSIONS: Superior weight reduction with 
      tirzepatide versus comparators appears to be independent of reported N/V/D or GI 
      AEs.
CI  - (c) 2023 Eli Lilly and Company and The Authors. Diabetes, Obesity and Metabolism 
      published by John Wiley & Sons Ltd.
FAU - Patel, Hiren
AU  - Patel H
AUID- ORCID: 0000-0003-2463-4916
AD  - Eli Lilly and Company, Indianapolis, Indiana, USA.
FAU - Khunti, Kamlesh
AU  - Khunti K
AUID- ORCID: 0000-0003-2343-7099
AD  - Diabetes Research Centre, University of Leicester, Leicester, UK.
FAU - Rodbard, Helena W
AU  - Rodbard HW
AUID- ORCID: 0000-0002-6187-8445
AD  - Endocrine and Metabolic Consultants, Rockville, Maryland, USA.
FAU - Bajaj, Harpreet S
AU  - Bajaj HS
AUID- ORCID: 0000-0002-1461-1465
AD  - LMC Diabetes and Endocrinology, Brampton, Ontario, Canada.
FAU - Bray, Ross
AU  - Bray R
AD  - Eli Lilly and Company, Indianapolis, Indiana, USA.
FAU - Kindracki, Zbigniew
AU  - Kindracki Z
AD  - Eli Lilly and Company, Warsaw, Poland.
FAU - Rodriguez, Angel
AU  - Rodriguez A
AUID- ORCID: 0000-0001-8721-9539
AD  - Lilly Spain, Madrid, Spain.
LA  - eng
GR  - Eli Lilly and Company/
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20231018
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 59392-49-3 (Gastric Inhibitory Polypeptide)
RN  - 0 (Glycated Hemoglobin)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulins)
RN  - OYN3CCI6QE (tirzepatide)
SB  - IM
MH  - Humans
MH  - *Diabetes Mellitus, Type 2/drug therapy/chemically induced
MH  - Diarrhea/chemically induced
MH  - Gastric Inhibitory Polypeptide/adverse effects
MH  - Glycated Hemoglobin
MH  - Hypoglycemic Agents/adverse effects
MH  - *Insulins
MH  - Nausea/chemically induced
MH  - Vomiting/chemically induced
MH  - Weight Loss
OTO - NOTNLM
OT  - GIP and GLP-1 receptor agonist
OT  - diarrhoea
OT  - gastrointestinal adverse events
OT  - incretin therapy
OT  - nausea
OT  - tirzepatide
OT  - type 2 diabetes
OT  - vomiting
OT  - weight loss
EDAT- 2023/10/19 06:44
MHDA- 2024/01/09 06:42
CRDT- 2023/10/19 04:04
PHST- 2023/09/22 00:00 [revised]
PHST- 2023/06/30 00:00 [received]
PHST- 2023/09/30 00:00 [accepted]
PHST- 2024/01/09 06:42 [medline]
PHST- 2023/10/19 06:44 [pubmed]
PHST- 2023/10/19 04:04 [entrez]
AID - 10.1111/dom.15333 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2024 Feb;26(2):473-481. doi: 10.1111/dom.15333. Epub 2023 
      Oct 18.