tirzepatide

• Any cancer

  no effect, p = 0.15

  tirzepatide had indifferent risks of any cancer versus placebo (RR, 0.66; 95% CI, 0.38 to 1.16; I2=0%; P=0.15

  PMID:39814031 · one of two readings recorded this

• Any cancer

  no effect, p = 0.97

  GLP-1RA (RR, 0.97; 95% CI, 0.22 to 4.34; I2=17%; P=0.97

  PMID:39814031 · one of two readings recorded this

• Any cancer

  no effect, p = 0.69

  insulin (RR, 0.89; 95% CI, 0.49 to 1.60; I2=0%; P=0.69

  PMID:39814031 · one of two readings recorded this

• Any cancer

  decreases, p = 0.02

  the 10 mg dose of the drug had a lower risk of any cancer than the placebo (RR, 0.34; 95% CI, 0.13 to 0.86; I2=0%; P=0.02)

  PMID:39814031 · one of two readings recorded this

• Any cancer

  no effect, p = 0.22, n = 13761

  Overall, tirzepatide use was associated with a similar risk of any cancer to the pooled control (RR, 0.78; 95% CI, 0.53 to 1.16; I2=0%; P=0.22

  PMID:39814031 · one of two readings recorded this

• Any cancer

  no effect, p = 0.14

  patients with diabetes (RR, 0.70; 95% CI, 0.44 to 1.12; I2=0%; P=0.14)

  PMID:39814031 · one of two readings recorded this

• Any cancer

  no effect, p = 0.95

  and without diabetes (RR, 1.02; 95% CI, 0.50 to 2.12; I2=0%; P=0.95)

  PMID:39814031 · one of two readings recorded this

• Breast cancer

  no effect, p = 0.31

  breast cancer (RR, 0.59; 95% CI, 0.21 to 1.65; I2=0%; P=0.31)

  PMID:39814031 · one of two readings recorded this

• Cholangiocarcinoma

  no effect, p = 0.24

  cholangiocarcinoma (RR, 0.33; 95% CI, 0.05 to 2.08; I2=0%; P=0.24)

  PMID:39814031 · one of two readings recorded this

• Colon cancer

  no effect, p = 0.54

  colon cancer (RR, 0.73; 95% CI, 0.26 to 2.04; I2=0%; P=0.54)

  PMID:39814031 · one of two readings recorded this

• Gastric cancer

  no effect, p = 0.85

  gastric cancer (RR, 1.24; 95% CI, 0.13 to 11.86; I2=0%; P=0.85)

  PMID:39814031 · one of two readings recorded this

• Glioblastoma

  no effect, p = 0.44

  glioblastoma (RR, 0.48; 95% CI, 0.08 to 3.04; I2=0%; P=0.44)

  PMID:39814031 · one of two readings recorded this

• Lung cancer

  no effect, p = 0.1

  lung cancer (RR, 0.39; 95% CI, 0.12 to 1.20; I2=0%; P=0.10)

  PMID:39814031 · one of two readings recorded this

• Lymphoma (any)

  no effect, p = 0.07

  lymphoma (any) (RR, 0.18; 95% CI, 0.03 to 1.17; I2=0%; P=0.07)

  PMID:39814031 · one of two readings recorded this

• Meningioma

  no effect, p = 0.57

  meningioma (RR, 0.62; 95% CI, 0.121 to 3.20; I2=0%; P=0.57)

  PMID:39814031 · one of two readings recorded this

• Ovarian cancer

  no effect, p = 0.68

  ovarian cancer (RR, 0.68; 95% CI, 0.11 to 4.32; I2=1%; P=0.68)

  PMID:39814031 · one of two readings recorded this

• overall risk of any cancer, risk ratio, tirzepatide versus pooled control (placebo, insulin or GLP-1 receptor agonist) in 13 RCTs; also risks of individual cancers and percent change in serum calcitonin

  no effect, any cancer RR 0.78, 95% CI 0.53 to 1.16, p = 0.22

  Not recorded as a finding: this platform holds no node for the endpoint

  Overall, tirzepatide use was associated with a similar risk of any cancer to the pooled control (RR, 0.78; 95% CI, 0.53 to 1.16; I2=0%; P=0.22, high certainty of evidence).

  PMID:39814031 · one of two readings recorded this

• overall risk of any cancer, tirzepatide versus pooled control (placebo, insulin, GLP-1 receptor agonist) and versus placebo alone, risk ratio; plus individual cancer types versus pooled control

  no effect, p = 0.15

  Not recorded as a finding: this platform holds no node for the endpoint

  When the control groups were analyzed separately, tirzepatide had indifferent risks of any cancer versus placebo (RR, 0.66; 95% CI, 0.38 to 1.16; I2=0%; P=0.15, high certainty of evidence), insulin (RR, 0.89; 95% CI, 0.49 to 1.60; I2=0%; P=0.69, high certainty of evidence), and GLP-1RA (RR, 0.97; 95% CI, 0.22 to 4.34; I2=17%; P=0.97, high certainty of evidence) (Table 2).

  PMID:39814031 · one of two readings recorded this

• Pancreatic cancer

  no effect, p = 0.89

  pancreatic cancer (RR, 0.85; 95% CI, 0.10 to 7.43; I2=30%; P=0.89)

  PMID:39814031 · one of two readings recorded this

• Papillary thyroid cancer

  no effect, p = 0.93

  thyroid cancer (papillary) (RR, 1.07; 95% CI, 0.22 to 5.12; I2=0%; P=0.93)

  PMID:39814031 · one of two readings recorded this

• Prostate cancer

  no effect, p = 0.33

  prostate cancer (RR, 0.53; 95% CI, 0.14 to 1.91; I2=0%; P=0.33)

  PMID:39814031 · one of two readings recorded this

• Renal cancer

  no effect, p = 0.66

  renal cancer (RR, 1.33; 95% CI, 0.37 to 4.78; I2=0%; P=0.66)

  PMID:39814031 · one of two readings recorded this

• Serum calcitonin percent increase

  increases, p = 0.0009

  Greater percent increases in serum calcitonin were observed with tirzepatide doses of 10 mg (SMD 18.28%; 95% CI, 7.45% to 29.11%; I2=100%; P=0.0009)

  PMID:39814031 · one of two readings recorded this

• Serum calcitonin percent increase

  increases, p = 0.00001

  and 15 mg (SMD 12.67%; 95% CI, 9.44% to 15.10%; I2=99%; P<0.00001)

  PMID:39814031 · one of two readings recorded this

• Skin cancer

  no effect, p = 0.61

  skin cancer (RR, 1.52; 95% CI, 0.31 to 7.34; I2=0%; P=0.61)

  PMID:39814031 · one of two readings recorded this

• Squamous cell carcinoma

  no effect, p = 0.7

  squamous cell carcinoma (RR, 1.45; 95% CI, 0.23 to 9.17; I2=0%; P=0.70)

  PMID:39814031 · one of two readings recorded this

• Urinary bladder cancer

  no effect, p = 0.46

  urinary bladder cancer (RR, 0.49; 95% CI, 0.07 to 3.27; I2=6%; P=0.46)

  PMID:39814031 · one of two readings recorded this

• Uterine cancer

  no effect, p = 0.89

  uterine cancer (RR, 1.12; 95% CI, 0.23 to 5.53; I2=0%; P=0.89)

  PMID:39814031 · one of two readings recorded this

• Elevated BMI

  decreases

  96% for the odds of elevated BMI (OR, 0.04; 95% CI: 0.02–0.08)

  PMID:40368575 · one of two readings recorded this

• HDL-C, standardized continuous

  increases

  the smallest effect size for HDL-C (β, 0.11; 95% CI: 0.07 to 0.16)

  PMID:40368575 · one of two readings recorded this

• Low HDL-C

  decreases

  34% for the odds of low HDL-C (OR, 0.66; 95% CI: 0.52–0.84)

  PMID:40368575 · one of two readings recorded this

• Metabolic syndrome (MetS), dose-response association

  decreases, p = 0.001

  with a statistically significant dose-response association (p < 0.001)

  PMID:40368575 · one of two readings recorded this

• Metabolic syndrome (MetS)

  decreases

  Tirzepatide was associated with 83% lower odds of MetS compared with placebo (OR, 0.17 [95% CI, 0.10–0.30])

  PMID:40368575 · one of two readings recorded this

• Metabolic syndrome (MetS)

  decreases

  72% lower odds compared with GLP-1 RAs (OR, 0.28 [95% CI, 0.20–0.37])

  PMID:40368575 · one of two readings recorded this

• Metabolic syndrome (MetS)

  decreases

  63% lower odds compared with insulin (OR, 0.37 [95% CI, 0.31–0.45])

  PMID:40368575 · one of two readings recorded this

• Metabolic syndrome (MetS)

  decreases, n = 7805

  Compared with the control arm, tirzepatide significantly decreased the odds of MetS by 72% (OR, 0.28; 95% CI, 0.24–0.33) over a weighted median treatment duration of 41.0 weeks

  PMID:40368575 · one of two readings recorded this

• Metabolic syndrome (MetS)

  decreases, n = 1834

  80% with tirzepatide 10 mg (OR, 0.20; 95% CI: 0.15–0.26)

  PMID:40368575 · one of two readings recorded this

• Metabolic syndrome (MetS)

  decreases, n = 1905

  85% with tirzepatide 15 mg (OR, 0.15; 95% CI: 0.12–0.20)

  PMID:40368575 · one of two readings recorded this

• Metabolic syndrome (MetS)

  decreases, n = 1838

  (OR, 0.36; 95% CI: 0.27–0.47) with tirzepatide 5 mg

  PMID:40368575 · one of two readings recorded this

• Metabolic syndrome (MetS)

  decreases, p = 0.008

  OR, 0.40 [95% CI, 0.31–0.52]; p for interaction=0.008

  PMID:40368575 · one of two readings recorded this

• Metabolic syndrome (MetS)

  decreases

  more pronounced in individuals <65 vs. ≥65 years old (OR, 0.23 [95% CI, 0.19–0.28]

  PMID:40368575 · one of two readings recorded this

• Metabolic syndrome (MetS)

  decreases, p = 0.009

  OR, 0.47 [95% CI, 0.32–0.70]; p for interaction=0.009

  PMID:40368575 · one of two readings recorded this

• Metabolic syndrome (MetS)

  decreases

  without vs. with baseline use of SGLT2is (OR, 0.26 [95% CI, 0.22–0.31]

  PMID:40368575 · one of two readings recorded this

• odds of metabolic syndrome (at least three of elevated waist circumference, elevated triglycerides, decreased HDL-C, elevated blood pressure, elevated fasting blood glucose) and of each cardiometabolic abnormality, tirzepatide versus a pooled comparator of placebo, GLP-1 receptor agonists and insulin, individual participant data meta-analysis of seven SURPASS trials

  decreases

  Not recorded as a finding: the paper never states the instrument the node requires

  Compared with the control arm, tirzepatide significantly decreased the odds of MetS by 72% (OR, 0.28; 95% CI, 0.24–0.33) over a weighted median treatment duration of 41.0 weeks.

  PMID:40368575 · one of two readings recorded this

• Participants with BMI reduction from baseline to one year

  increases

  94.4% in the tirzepatide arm, compared with 43.5% in the comparator arm, experienced BMI reduction

  PMID:40368575 · one of two readings recorded this

• Participants with waist circumference reduction from baseline to one year

  increases

  91.4% of participants in the tirzepatide arm experienced WC reduction, as opposed to 54.8% in the comparator arm

  PMID:40368575 · one of two readings recorded this

• presence of metabolic syndrome (at least 3 of 5 cardiometabolic abnormalities) and each abnormality (waist circumference, triglycerides, HDL-C, blood pressure, fasting glucose, BMI >= 25), odds ratios from individual participant data meta-analysis of seven SURPASS trials; headline comparator pools placebo, GLP-1 receptor agonists and insulin

  decreases

  Not recorded as a finding: the paper never states the instrument the node requires

  Tirzepatide was associated with 83% lower odds of MetS compared with placebo (OR, 0.17 [95% CI, 0.10–0.30]), 63% lower odds compared with insulin (OR, 0.37 [95% CI, 0.31–0.45]), and 72% lower odds compared with GLP-1 RAs (OR, 0.28 [95% CI, 0.20–0.37]).

  PMID:40368575 · one of two readings recorded this

• Systolic blood pressure, standardized continuous

  decreases

  the most pronounced effect size for SBP (β, −0.32; 95% CI: −0.35 to −0.28)

  PMID:40368575 · one of two readings recorded this

• Weighted prevalence of metabolic syndrome, baseline to one year

  decreases

  The weighted prevalence of MetS decreased from 82.0% at baseline to 51.3% at one year in the tirzepatide arm vs. 78.8% to 66.4% in the comparator arm

  PMID:40368575 · one of two readings recorded this

• Alopecia

  increases, p = 0.0001

  and 5.50 (95% CI: 3.51–8.64, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Change in body mass index

  decreases, p = 0.0002

  −5.89 kg/m2 (95% CI: −8.97 to −2.81, p = 0.0002)

  PMID:40510020 · one of two readings recorded this

• Change in body weight

  decreases, p = 0.0001

  showing an MD of −13.95 kg and a 95% CI of −18.83 to −9.07 (p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Change in diastolic blood pressure

  decreases, p = 0.0003

  −4.02 mmHg (95% CI: −6.20 to −1.85, p = 0.0003)

  PMID:40510020 · one of two readings recorded this

• Change in fasting glucose

  decreases, p = 0.0001

  fasting glucose (mg/dL) showed a change of −10.09 (95% CI: −11.81 to −8.38, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Change in HbA1C

  decreases, p = 0.0001

  there was a modest reduction in HbA1C (%), with a change of −0.41 (95% CI: −0.50 to −0.33, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Change in systolic blood pressure

  decreases, p = 0.0001

  changes of −6.63 mmHg (95% CI: −8.41 to −4.85, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Change in waist circumference

  decreases, p = 0.0001

  −12.31 cm (95% CI: −13.93 to −10.68, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Cholelithiasis

  no effect, p = 0.55

  1.18 (95% CI: 0.69–2.03, p = 0.55)

  PMID:40510020 · one of two readings recorded this

• Constipation

  increases, p = 0.0001

  and 2.85 (95% CI: 2.38–3.42, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Diarrhea

  increases, p = 0.0001

  diarrhea and constipation were 2.92 (95% CI: 2.53–3.37, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Discontinuation due to adverse events

  increases, p = 0.0001

  with an RR of 2.29 (95% CI: 1.74–3.01, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Dyspepsia

  increases, p = 0.0001

  RRs of 2.59 (95% CI: 2.05–3.27, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Eructation

  increases, p = 0.0001

  8.05 (95% CI: 4.80–13.50, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Gallbladder disorder

  no effect, p = 0.43

  RRs of 1.26 (95% CI: 0.70–2.27, p = 0.43)

  PMID:40510020 · one of two readings recorded this

• gastrointestinal adverse events (nausea, vomiting, diarrhoea, constipation) versus placebo

  increases, nausea RR 3.11, 95% CI 2.74-3.54

  Not recorded as a finding: no outcome node for individual gastrointestinal adverse events for a subcutaneous drug

  Our meta‐analysis revealed that compared with placebo, the incidence of nausea and vomiting with once‐weekly tirzepatide was significantly higher, with RR of 3.11 (95% CI: 2.74–3.54, p < 0.0001) and 5.94 (95% CI: 4.50–7.85, p < 0.0001), respectively.

  PMID:40510020 · one of two readings recorded this

• HbA1c change (%), fasting glucose (mg/dL), systolic and diastolic blood pressure (mmHg), and percentage change in lipid panel versus placebo

  decreases, HbA1c change -0.41 (95% CI -0.50 to -0.33)

  Not recorded as a finding: the sentences reporting these never name tirzepatide (agentless 'there was' or 'the MD was'), so they are not self-supporting

  Notably, there was a modest reduction in HbA1C (%), with a change of −0.41 (95% CI: −0.50 to −0.33, p < 0.0001) (Figure S2A).

  PMID:40510020 · one of two readings recorded this

• HbA1c change versus placebo

  decreases, change -0.41, 95% CI -0.50 to -0.33

  Not recorded as a finding: anchoring sentence is agentless ('there was a modest reduction') and does not name tirzepatide

  Notably, there was a modest reduction in HbA1C (%), with a change of −0.41 (95% CI: −0.50 to −0.33, p < 0.0001) (Figure S2A).

  PMID:40510020 · one of two readings recorded this

• Hypoglycemia

  increases, p = 0.0001

  with RRs of 6.26 (95% CI: 2.44–16.01, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Injection site reactions

  increases, p = 0.0001

  14.17 (95% CI: 7.48–26.85, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Mortality

  no effect, p = 0.32

  (RR: 0.65, 95% CI: 0.28–1.51, p = 0.32)

  PMID:40510020 · one of two readings recorded this

• Nausea

  increases, p = 0.0001

  RR of 3.11 (95% CI: 2.74–3.54, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Pancreatitis

  no effect, p = 0.52

  1.51 (95% CI: 0.42–5.38, p = 0.52)

  PMID:40510020 · one of two readings recorded this

• Percentage change in body weight

  decreases, p = 0.0001

  with an MD of −16.32% and a 95% CI of −18.35 to −14.29 (p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Percentage change in free fatty acids

  decreases, p = 0.0001

  −17.35 (95% CI: −22.17 to −12.54, p < 0.0001) for free fatty acids

  PMID:40510020 · one of two readings recorded this

• Percentage change in HDL cholesterol

  increases, p = 0.0001

  9.80 (95% CI: 7.88–11.71, p < 0.0001) for HDL cholesterol

  PMID:40510020 · one of two readings recorded this

• Percentage change in LDL cholesterol

  decreases, p = 0.024

  −6.61 (95% CI: −12.34 to −0.88, p = 0.024) for LDL cholesterol

  PMID:40510020 · one of two readings recorded this

• Percentage change in total cholesterol

  decreases, p = 0.0042

  The MD in the percentage change compared with placebo was −5.57 (95% CI: −9.39 to −1.75, p = 0.0042) for total cholesterol

  PMID:40510020 · one of two readings recorded this

• Percentage change in triglycerides

  decreases, p = 0.0001

  −24.48 (95% CI: −32.36 to −16.59, p < 0.0001) for triglycerides

  PMID:40510020 · one of two readings recorded this

• Percentage change in VLDL

  decreases, p = 0.0001

  −24.52 (95% CI: −31.73 to −17.31, p < 0.0001) for VLDL

  PMID:40510020 · one of two readings recorded this

• proportion achieving weight reduction of at least 5, 10, 15, 20 and 25%, odds ratio versus placebo

  increases, OR 16.41 (95% CI 11.82-22.77) for 5% reduction

  Not recorded as a finding: no_outcome_node: no weight-loss-threshold responder node in the outcome list

  For a 5% reduction: OR 16.41 (95% CI: 11.82–22.77, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Serious adverse events

  no effect, p = 0.45

  compared with placebo was 0.93 (95% CI: 0.76–1.13, p = 0.45)

  PMID:40510020 · one of two readings recorded this

• Serious gastrointestinal events

  increases, p = 0.0001

  statistically significant at 3.07 (95% CI: 2.03–4.66, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• systolic and diastolic blood pressure change versus placebo

  decreases, systolic -6.63 mmHg, 95% CI -8.41 to -4.85

  Not recorded as a finding: anchoring sentence names no compound ('We observed reductions') and pools systolic and diastolic; no setting-specific node

  We observed reductions in both systolic and diastolic blood pressures, with changes of −6.63 mmHg (95% CI: −8.41 to −4.85, p < 0.0001) (Figure S3A) and −4.02 mmHg (95% CI: −6.20 to −1.85, p = 0.0003) (Figure S3B), respectively.

  PMID:40510020 · one of two readings recorded this

• Vomiting

  increases, p = 0.0001

  and 5.94 (95% CI: 4.50–7.85, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• waist circumference in cm, mean difference versus placebo

  decreases, MD -12.31 cm, 95% CI -13.93 to -10.68

  Not recorded as a finding: no_outcome_node: no waist circumference node in the outcome list

  Additionally, once‐weekly tirzepatide resulted in decreases in BMI and waist circumference, with MDs of −5.89 kg/m2 (95% CI: −8.97 to −2.81, p = 0.0002) (Figure S1A) and −12.31 cm (95% CI: −13.93 to −10.68, p < 0.0001) (Figure S1B), respectively.

  PMID:40510020 · one of two readings recorded this

• Weight reduction of at least 10%

  increases, p = 0.0001

  For a 10% reduction: OR 15.66 (95% CI: 10.64–23.04, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Weight reduction of at least 15%

  increases, p = 0.0001

  For a 15% reduction: OR 21.71 (95% CI: 13.18–35.77, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Weight reduction of at least 20%

  increases, p = 0.0001

  For a 20% reduction: OR 27.39 (95% CI: 15.64–47.98, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Weight reduction of at least 25%

  increases, p = 0.0001

  For a 25% reduction: OR 24.37 (95% CI: 13.56–43.80, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Weight reduction of at least 5%

  increases, p = 0.0001

  For a 5% reduction: OR 16.41 (95% CI: 11.82–22.77, p < 0.0001)

  PMID:40510020 · one of two readings recorded this

• Body weight change from baseline

  decreases

  −10.42 kg (95% CI, −14.72 to −6.12)

  PMID:40746703 · one of two readings recorded this

• Body weight change from baseline

  decreases

  −12.52 kg [9(5% CI, −16.58 to −8.46)

  PMID:40746703 · one of two readings recorded this

• Body weight change from baseline

  decreases

  MD of −7.66 kg (95% CI, −10.71 to −4.60)

  PMID:40746703 · one of two readings recorded this

• Body weight change from baseline

  decreases

  −6.02 kg [95% CI, −8.78 to −3.26]

  PMID:40746703 · one of two readings recorded this

• Body weight change from baseline

  decreases

  −8.31 kg [95% CI, −11.19 to −5.42]

  PMID:40746703 · one of two readings recorded this

• Body weight change from baseline

  decreases

  −3.03 kg [95% CI, −5.68 to −0.39]

  PMID:40746703 · one of two readings recorded this

• Constipation

  increases

  constipation occurred more with the 10-mg dose (RR, 3.22, 95% CI [2.30, 4.53])

  PMID:40746703 · one of two readings recorded this

• Diarrhoea

  increases

  diarrhoea: RR, 2.89, 95% CI [2.24, 3.74]

  PMID:40746703 · one of two readings recorded this

• Diarrhoea

  increases

  diarrhoea happened slightly more in tirzepatide 10 mg and 15 mg than in GLP-1 RAs (RR, 1.40, 95% CI [1.06, 1.85])

  PMID:40746703 · one of two readings recorded this

• Diarrhoea

  increases

  (RR, 1.35, 95% CI [1.02, 1.79])

  PMID:40746703 · one of two readings recorded this

• mean difference in body weight change from baseline (kg) at tirzepatide 5, 10 and 15 mg separately versus placebo and versus GLP-1 receptor agonists, RCTs of at least 20 weeks

  decreases, tirzepatide 5 mg MD -7.66 kg (95% CI -10.71 to -4.60); 10 mg MD -10.42 kg (95% CI -14.72 to -6.12); 15 mg MD -12.52 kg versus placebo

  Not recorded as a finding: every result is a subgroup, with no whole-population estimate

  Tirzepatide 5, 10 and 15 mg decreased weight compared to placebo with a MD of −7.66 kg (95% CI, −10.71 to −4.60), −10.42 kg (95% CI, −14.72 to −6.12) and −12.52 kg [9(5% CI, −16.58 to −8.46), respectively, and p value of less than 0.001 for all tests.

  PMID:40746703 · one of two readings recorded this

• mean difference in body weight from baseline (kg) versus placebo, reported separately for tirzepatide 5, 10 and 15 mg; also versus GLP-1 receptor agonists and categorical 5/10/15% weight loss

  decreases, MD -7.66 kg (5 mg), -10.42 kg (10 mg), -12.52 kg (15 mg) versus placebo

  Not recorded as a finding: every result is a subgroup, with no whole-population estimate

  Tirzepatide 5, 10 and 15 mg decreased weight compared to placebo with a MD of −7.66 kg (95% CI, −10.71 to −4.60), −10.42 kg (95% CI, −14.72 to −6.12) and −12.52 kg [9(5% CI, −16.58 to −8.46), respectively, and p value of less than 0.001 for all tests.

  PMID:40746703 · one of two readings recorded this

• Nausea

  increases

  nausea: RR, 3.55, 95% CI [2.79, 4.51]

  PMID:40746703 · one of two readings recorded this

• Nausea

  increases

  the risk of developing nausea was higher in tirzepatide 15 mg than in GLP-1 RAs (RR, 1.40, 95% CI [1.13, 1.74])

  PMID:40746703 · one of two readings recorded this

• Participants achieving 5% weight reduction

  increases

  the percentages of participants who achieved 5% weight reduction were higher in the tirzepatide groups (76%, 80% and 86% for tirzepatide 5, 10 and 15 mg, respectively) in comparison to 26% in the placebo arm

  PMID:40746703 · one of two readings recorded this

• Participants achieving 5% weight reduction

  increases

  the percentage of participants who reached a target weight loss of 5% was 64% with tirzepatide 5 mg, 80% with tirzepatide 10 mg and 84% with tirzepatide 15 mg compared to 44% with GLP-1 RAs

  PMID:40746703 · one of two readings recorded this

• Publication bias, Egger test, tirzepatide vs GLP-1 receptor agonists

  no effect, p = 0.843

  Egger's test was calculated for both comparisons, demonstrating no publication bias as the p value was higher than 0.05 (p=0.278 and p=0.843, respectively)

  PMID:40746703 · one of two readings recorded this

• Publication bias, Egger test, tirzepatide vs placebo

  no effect, p = 0.278

  Egger's test was calculated for both comparisons, demonstrating no publication bias as the p value was higher than 0.05 (p=0.278 and p=0.843, respectively)

  PMID:40746703 · one of two readings recorded this

• Vomiting

  increases

  vomiting: RR, 6.68, 95% CI [4.05, 11.04]

  PMID:40746703 · one of two readings recorded this

• Abdominal pain

  increases, p = 0.006

  10 mg: OR=1.76, 95%CI:1.18 to 2.63, p=0.006

  PMID:40747302 · one of two readings recorded this

• Abdominal pain

  increases, p = 0.0002

  15 mg: OR=2.02, 95%CI: 1.40 to 2.92, p=0.0002

  PMID:40747302 · one of two readings recorded this

• Abdominal pain

  increases, p = 0.02

  5 mg group showed potential risk (OR=1.72, 95%CI:1.09 to 2.71, p=0.02

  PMID:40747302 · one of two readings recorded this

• Abdominal pain

  increases, p = 0.0001

  higher incidence of abdominal pain comparing with placebo (OR=1.85, 95%CI:1.47 to 2.34, p<0.0001

  PMID:40747302 · one of two readings recorded this

• Abdominal pain

  increases

  10 mg (OR=1.77)

  PMID:40747302 · one of two readings recorded this

• Abdominal pain

  increases, p = 0.0005

  Among diabetics only the 15 mg dose was significant (OR=2.97, p = 0.0005)

  PMID:40747302 · one of two readings recorded this

• Abdominal pain

  increases

  significant effects at 5 mg (OR=1.75)

  PMID:40747302 · one of two readings recorded this

• adverse events leading to treatment discontinuation, tirzepatide versus placebo

  increases, OR 1.98, 95% CI 1.63 to 2.61

  Not recorded as a finding: the anchoring sentence says 'discontinuing treatment' without naming adverse events, so withdrawal-due-to-adverse-events was not claimed

  Aggregated data indicated that tirzepatide group had higher likelihood of discontinuing treatment comparing with placebo (OR=1.98, 95%CI: 1.63 to 2.61, p<0.0001,

  PMID:40747302 · one of two readings recorded this

• Adverse events leading to treatment discontinuation

  increases, p = 0.0001

  10 mg: OR=1.93, 95%CI: 1.38 to 2.69, p=0.0001

  PMID:40747302 · one of two readings recorded this

• Adverse events leading to treatment discontinuation

  increases, p = 0.0001

  15 mg: OR=2.31, 95%CI:1.69 to 3.14, p<0.0001

  PMID:40747302 · one of two readings recorded this

• Adverse events leading to treatment discontinuation

  increases, p = 0.03

  The 5 mg group exhibited a lower discontinuation rate (OR=1.57, 95%CI:1.05 to 2.36, p=0.03

  PMID:40747302 · one of two readings recorded this

• Adverse events leading to treatment discontinuation

  increases, p = 0.0001

  tirzepatide group had higher likelihood of discontinuing treatment comparing with placebo (OR=1.98, 95%CI: 1.63 to 2.61, p<0.0001

  PMID:40747302 · one of two readings recorded this

• Adverse events leading to treatment discontinuation

  increases, p = 0.0001

  10 mg (OR=2.26, 95% CI 1.48–3.43, p = 0.0001)

  PMID:40747302 · one of two readings recorded this

• Adverse events leading to treatment discontinuation

  increases, p = 0.001

  only the 15 mg dose significantly increased discontinuations (OR=2.17, 95% CI 1.37–3.45, p = 0.001)

  PMID:40747302 · one of two readings recorded this

• Adverse events leading to treatment discontinuation

  increases

  15 mg (OR=2.42, 95% CI 1.59–3.67, p < 0.0001)

  PMID:40747302 · one of two readings recorded this

• Any adverse event

  increases, p = 0.0001

  patients receiving tirzepatide 5 mg reported higher incidence of adverse events comparing with placebo (OR=1.48, 95%CI:1.22 to 1.80, p<0.0001

  PMID:40747302 · one of two readings recorded this

• Any adverse event

  increases, p = 0.0001

  patients receiving tirzepatide had a higher likelihood of experiencing adverse effects comparing with placebo group (OR=1.34, 95%CI:1.21 to 1.47, p<0.0001

  PMID:40747302 · one of two readings recorded this

• Any adverse event

  no effect, p = 0.0003

  At 10 mg, diabetic patients had a modest yet significant increase (OR=1.19, 95% CI 0.92–1.53, p = 0.0003)

  PMID:40747302 · one of two readings recorded this

• Any adverse event

  increases, p = 0.00001

  (OR=1.75, 95% CI 1.40–2.20, p < 0.00001)

  PMID:40747302 · one of two readings recorded this

• Any adverse event

  increases, p = 0.00001

  (OR 1.26, 95% CI 1.00–1.59, p < 0.00001)

  PMID:40747302 · one of two readings recorded this

• Any adverse event

  no effect, p = 0.63

  (OR=1.05, 95% CI 0.85–1.30, p = 0.63)

  PMID:40747302 · one of two readings recorded this

• Any adverse event

  no effect, p = 0.05

  (OR=1.38, 95% CI 0.97–1.96, p = 0.05)

  PMID:40747302 · one of two readings recorded this

• Any adverse event

  increases, p = 0.0003

  patients at 5 mg experienced a significant increase (OR=1.53, 95% CI 1.22–1.92, p = 0.0003)

  PMID:40747302 · one of two readings recorded this

• Body weight change

  decreases, p = 0.00001

  The 10 mg group exhibited a more pronounced effect (WMD=-10.70, 95% CI:-11.41 to -10.00, p<0.00001)

  PMID:40747302 · one of two readings recorded this

• Body weight change

  decreases, p = 0.0001

  The 15 mg group showed the greatest weight reduction, with a substantial and highly significant effect (WMD=-11.48, 95%CI:-12.11 to -10.85, p<0.0001)

  PMID:40747302 · one of two readings recorded this

• Body weight change

  decreases, p = 0.0001

  patients receiving tirzepatide 5 mg experienced body weight reduction comparing with placebo (WMD=-8.21, 95%CI:-9.02 to -7.40, p<0.0001)

  PMID:40747302 · one of two readings recorded this

• Body weight change

  decreases, p = 0.00001

  Pooled analysis demonstrated a reduction in body weight in patients receiving tirzepatide comparing with placebo (WMD=-10.80, 95%CI:-10.80 to -9.99, p < 0.00001)

  PMID:40747302 · one of two readings recorded this

• Body weight change

  decreases, p = 0.00001

  –15.94 kg (95% CI: –17.25 to –14.62, p < 0.00001) for 10 mg

  PMID:40747302 · one of two readings recorded this

• Body weight change

  decreases, p = 0.00001

  –8.57 kg (95% CI: –9.41 to –7.74, p < 0.00001) at 10 mg

  PMID:40747302 · one of two readings recorded this

• Body weight change

  decreases, p = 0.00001

  –17.86 kg (95% CI: –19.19 to –16.54, p < 0.00001) for 15 mg

  PMID:40747302 · one of two readings recorded this

• Body weight change

  decreases, p = 0.00001

  –9.60 kg (95% CI: –10.32 to –8.89, p < 0.00001) at 15 mg

  PMID:40747302 · one of two readings recorded this

• Body weight change

  decreases, p = 0.00001

  –12.10 kg (95% CI: –13.47 to –10.72, p < 0.00001) for 5 mg

  PMID:40747302 · one of two readings recorded this

• Body weight change

  decreases, p = 0.00001

  among patients with type 2 diabetes, mean weight changes were –6.17 kg (95% CI: –7.16 to –5.17, p < 0.00001) at 5 mg

  PMID:40747302 · one of two readings recorded this

• Constipation

  increases, p = 0.0001

  greater incidence of constipation comparing with placebo group (OR=3.08, 95%CI:2.28 to 4.17, p<0.0001

  PMID:40747302 · one of two readings recorded this

• Constipation

  increases, p = 0.0001

  higher incidence of constipation comparing with placebo (OR=3.10, 95%CI:2.55 to 3.75, p<0.0001

  PMID:40747302 · one of two readings recorded this

• Decreased appetite

  increases, p = 0.0001

  greater incidence of decreased appetite comparing with placebo group (OR=3.67, 95%CI: 2.49 to 5.42, p<0.0001

  PMID:40747302 · one of two readings recorded this

• Decreased appetite

  increases, p = 0.0001

  higher incidence of decreased appetite comparing with placebo (OR=4.28, 95%CI:3.53 to 5.18, p<0.0001

  PMID:40747302 · one of two readings recorded this

• Dizziness

  increases, p = 0.001

  10 mg: OR=2.40, 95%CI:1.57 to 3.67, p<0.001

  PMID:40747302 · one of two readings recorded this

• Dizziness

  no effect, p = 0.04

  15 mg: OR=1.49, 95%CI:0.97 to 2.30, p=0.04

  PMID:40747302 · one of two readings recorded this

• Dizziness

  no effect, p = 0.06

  the 5 mg group showed no potential risk (OR=1.56, 95%CI:0.95 to 2.57, p=0.06

  PMID:40747302 · one of two readings recorded this

• Dizziness

  increases, p = 0.0001

  higher incidence of dizziness comparing with placebo (OR=1.81, 95%CI:1.40 to 2.35, p<0.0001

  PMID:40747302 · one of two readings recorded this

• Dizziness

  increases, p = 0.0008

  (OR=2.28, 95% CI: 1.40–3.70, p=0.0008)

  PMID:40747302 · one of two readings recorded this

• Dizziness

  no effect, p = 0.05

  (OR=0.92, 95% CI: 0.13–6.82, p>0.05)

  PMID:40747302 · one of two readings recorded this

• Dizziness

  no effect, p = 0.05

  (OR=1.62, 95% CI: 0.97–2.70, p>0.05)

  PMID:40747302 · one of two readings recorded this

• Dyspepsia

  increases, p = 0.0001

  greater incidence of dyspepsia comparing with placebo group (OR=2.12, 95%CI:1.49 to 3.03, p<0.0001

  PMID:40747302 · one of two readings recorded this

• Dyspepsia

  increases, p = 0.0001

  higher incidence of dyspepsia comparing with placebo (OR=2.50, 95 CI:2.07 to 3.01, p<0.0001

  PMID:40747302 · one of two readings recorded this

• Headache

  no effect, p = 0.97

  (OR=1.00, 95%CI:0.84 to 1.20, p=0.97

  PMID:40747302 · one of two readings recorded this

• Hypoglycemia

  no effect, p = 0.07

  (OR= 2.05, 95%CI:0.95 to 4.42, p=0.07

  PMID:40747302 · one of two readings recorded this

• Hypoglycemia

  increases, p = 0.03

  (OR=9.30, 95% CI: 1.18–73.66, p=0.03)

  PMID:40747302 · one of two readings recorded this

• Nasopharyngitis

  decreases, p = 0.01

  (OR=0.58, 95%CI:0.38 to 0.88, p=0.01

  PMID:40747302 · one of two readings recorded this

• Nasopharyngitis

  no effect, p = 0.07

  15 mg: OR=0.70, 95%CI: 0.47 to 1.03, p=0.07

  PMID:40747302 · one of two readings recorded this

• Nasopharyngitis

  no effect, p = 0.74

  5 mg: OR=0.93, 95%CI:0.59 to 1.45, p=0.74

  PMID:40747302 · one of two readings recorded this

• Nasopharyngitis

  decreases, p = 0.005

  (OR=0.71, 95%CI:0.50 to 0.90, p=0.005

  PMID:40747302 · one of two readings recorded this

• Nasopharyngitis

  decreases, p = 0.004

  (OR=0.49, 95% CI: 0.30–0.79, p=0.004)

  PMID:40747302 · one of two readings recorded this

• Nasopharyngitis

  no effect, p = 0.14

  (OR=0.73, 95% CI: 0.48–1.11, p=0.14)

  PMID:40747302 · one of two readings recorded this

• Nasopharyngitis

  no effect, p = 0.35

  (OR=0.77, 95% CI: 0.45–1.32, p=0.35)

  PMID:40747302 · one of two readings recorded this

• Nausea

  increases, p = 0.0001

  10 mg: OR=3.45, 95 CI:2.82 to 4.21, p<0.0001

  PMID:40747302 · one of two readings recorded this

• Nausea

  increases, p = 0.0001

  15 mg: OR=3.45, 95%CI:2.84 to 4.18, p<0.0001

  PMID:40747302 · one of two readings recorded this

• Nausea

  increases, p = 0.0001

  5 mg group exhibited a higher incidence of nausea comparing with placebo (OR=2.24, 95%CI:1.78 to 2.81, p<0.0001

  PMID:40747302 · one of two readings recorded this

• Nausea

  increases, p = 0.0001

  patients treated with tirzepatide had a higher incidence of nausea comparing with placebo (OR=3.08, 95%CI:3.74 to 3.46, p<0.0001

  PMID:40747302 · one of two readings recorded this

• proportion achieving at least 5% body weight loss, odds ratio versus placebo

  increases, OR 11.32, 95% CI 10.12 to 12.66

  Not recorded as a finding: no_outcome_node: no weight-loss-threshold responder node in the outcome list

  Aggregated data indicated that tirzepatide treatment was correlated with higher likelihood of achieving ≥5% body weight loss comparing with placebo (OR=11.32, 95%CI:10.12 to 12.66, p<0.0001).

  PMID:40747302 · one of two readings recorded this

• serious adverse events, odds ratio versus placebo

  OR 0.97, 95% CI 0.83-1.14, p = 0.74

  Not recorded as a finding: one-sided negation (no potentiation in risk) is not no_effect

  Aggregated data revealed no potentiation in risk of SAEs with tirzepatide treatment comparing with placebo (OR=0.97, 95%CI:0.83-1.14, p=0.74, Supplementary Figure S2A), indicating that the treatment was generally well tolerated.

  PMID:40747302 · one of two readings recorded this

• Serious adverse events

  no effect, p = 0.74

  no potentiation in risk of SAEs with tirzepatide treatment comparing with placebo (OR=0.97, 95%CI:0.83-1.14, p=0.74

  PMID:40747302 · one of two readings recorded this

• Vomiting

  increases, p = 0.0001

  (OR=6.56, 95%CI:461 to 9.34, p<0.0001

  PMID:40747302 · one of two readings recorded this

• Vomiting

  increases, p = 0.0001

  (OR=6.06, 95%CI:4.16 to 8.82, p<0.0001

  PMID:40747302 · one of two readings recorded this

• Vomiting

  increases, p = 0.0001

  (OR=5.06, 95%CI:3.48 to 7.36, p<0.0001

  PMID:40747302 · one of two readings recorded this

• Vomiting

  increases, p = 0.0001

  (OR=5.51, 95%CI:4.40 to 6.91, p<0.0001

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 10%

  increases, p = 0.0001

  The 10 mg group exhibited a more pronounced effect (OR= 15.87, 95%CI:12.85 to 19.60, p<0.0001)

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 10%

  increases, p = 0.0001

  The 15 mg group showed similar effects with 10 mg group, with a substantially higher proportion of patients achieving ≥10% weight loss (OR=19.31, 95%CI:15.56 to 23.95, p<0.0001)

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 10%

  increases, p = 0.0001

  patients receiving tirzepatide 5 mg showed increase in individuals achieving ≥10% weight loss comparing with placebo (OR=9.64, 95%CI: 7.63 to 12.20, p<0.0001)

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 10%

  increases, p = 0.0001

  tirzepatide treatment was correlated with a significantly higher likelihood of achieving ≥10% body weight loss comparing with placebo (OR=14.77, 95%CI:13.02 to 16.76, p<0.0001)

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 10%

  increases, p = 0.0001

  the overall OR was 19.88 (95% CI: 14.53–27.21, p < 0.0001)

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 10%

  increases, p = 0.00001

  21.51 (95% CI: 14.23–32.51, p < 0.00001) at 10 mg

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 10%

  increases, p = 0.00001

  13.88 (95% CI: 10.86–17.74, p < 0.00001)

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 10%

  increases, p = 0.00001

  and 25.53 (95% CI: 16.80–38.79, p < 0.00001) at 15 mg

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 10%

  increases, p = 0.00001

  and 17.02 (95% CI: 13.24–21.88, p < 0.00001) at 5, 10, and 15 mg

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 10%

  increases, p = 0.00001

  In diabetic patients, ORs were 35.62 (95% CI: 10.00–126.86, p < 0.00001) at 5 mg

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 10%

  increases, p = 0.00001

  showed ORs of 8.61 (95% CI: 6.77–10.93, p < 0.00001)

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 15%

  increases, p = 0.0001

  The 10 mg group exhibited a more pronounced effect (OR=20.77, 95%CI:15.84 to 27.23, p<0.0001)

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 15%

  increases, p = 0.0001

  The 15 mg group showed the greatest impact, with a substantially higher proportion of patients achieving ≥15% weight loss (OR=26.11, 95%CI:19.86 to 34.32, p<0.0001)

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 15%

  increases, p = 0.0001

  patients receiving tirzepatide 5 mg showed increase in individuals achieving ≥15% weight loss comparing with placebo (OR=9.54, 95%CI: 7.14 to 12.73, p<0.0001)

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 15%

  increases, p = 0.0001

  tirzepatide treatment was correlated with a significantly higher likelihood of achieving ≥15% body weight loss comparing with placebo (OR=18.07, 95%CI:15.41 to 21.18, p<0.0001)

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 15%

  increases, p = 0.0001

  the pooled OR was 23.13 (95% CI: 16.17–33.07, p < 0.0001)

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 15%

  increases, p = 0.00001

  30.19 (95% CI: 15.33–59.44, p < 0.00001) at 10 mg

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 15%

  increases, p = 0.00001

  18.58 (95% CI: 13.86–24.90, p < 0.00001)

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 15%

  increases, p = 0.00001

  and 41.04 (95% CI: 20.76–81.11, p < 0.00001) at 15 mg

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 15%

  increases, p = 0.00001

  and 22.65 (95% CI: 16.86–30.44, p < 0.00001) at 5, 10, and 15 mg

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 15%

  increases, p = 0.00001

  Diabetic patients demonstrated ORs of 20.03 (95% CI: 3.87–103.64, p < 0.00001) at 5 mg

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 15%

  increases, p = 0.00001

  corresponding ORs were 9.12 (95% CI: 6.80–12.23, p < 0.00001)

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 5%

  increases, p = 0.0001

  The 10 mg group exhibited a more pronounced effect (OR=11.21, 95%CI:9.33 to 13.47, p<0.0001)

  PMID:40747302 · one of two readings recorded this

• Weight loss of at least 5%

  increases, p = 0.0001

  The 15 mg group showed the greatest impact, with a substantially higher proportion of patients achieving ≥5% weight loss (OR=13.19, 95%CI:10.91 to 15.94, p<0.0001)

  PMID:40747302 · one of two readings recorded this

The whole record — 383 rows