• any hypoglycaemia, plasma glucose 3.9 mmol/l or below

  no effect

  Not recorded as a finding: no outcome node for hypoglycaemia incidence

  Incidence of any hypoglycaemia (defined as plasma glucose ≤3.9 mmol/l) with tirzepatide did not differ vs placebo (ESM Fig. 3) and was lower with tirzepatide compared with basal insulin (OR ranging from 0.17 with tirzepatide 5 mg to 0.25 with tirzepatide 15 mg) (ESM Fig. 4).

  PMID 35579691 · one of two readings recorded this

• any hypoglycaemia

  no effect

  Incidence of any hypoglycaemia (defined as plasma glucose ≤3.9 mmol/l) with tirzepatide did not differ vs placebo

  PMID 35579691 · one of two readings recorded this

• any hypoglycaemia

  decreases

  OR ranging from 0.17 with tirzepatide 5 mg to 0.25 with tirzepatide 15 mg

  PMID 35579691 · one of two readings recorded this

• any hypoglycaemia

  decreases

  OR ranging from 0.17 with tirzepatide 5 mg to 0.25 with tirzepatide 15 mg

  PMID 35579691 · one of two readings recorded this

• body weight change

  decreases

  10 mg (8.43 kg [95% CI 6.77, 10.09], I2 68%)

  PMID 35579691 · one of two readings recorded this

• body weight change

  decreases

  15 mg (9.36 kg [95% CI 6.20, 12.53], I2 91%)

  PMID 35579691 · one of two readings recorded this

• body weight change

  decreases

  tirzepatide 5 mg (6.31 kg [95% CI 4.38, 8.25], I2 70%)

  PMID 35579691 · one of two readings recorded this

• body weight change

  decreases

  7.16 kg (95% CI 4.86, 9.46 [I2 72%]) with tirzepatide 15 mg

  PMID 35579691 · one of two readings recorded this

• body weight change

  decreases

  1.68 kg (95% CI 0.84, 2.52 [I2 0%]) with tirzepatide 5 mg

  PMID 35579691 · one of two readings recorded this

• body weight loss of at least 10% and 15%

  increases

  All tirzepatide doses were more efficacious than GLP-1 RAs in achieving a body weight loss of at least 10% and 15%

  PMID 35579691 · one of two readings recorded this

• body weight loss of at least 5%

  increases

  4.79 (95% CI 1.95, 11.73 [I2 74%])

  PMID 35579691 · one of two readings recorded this

• body weight loss of at least 5%

  increases

  4.57 (95% CI 3.38, 6.18 [I2 0%])

  PMID 35579691 · one of two readings recorded this

• body weight loss of at least 5%

  increases

  1.96 (95% CI 1.01, 3.80 [I2 61%])

  PMID 35579691 · one of two readings recorded this

• diarrhoea

  no effect

  Tirzepatide 10 mg | Placebo | 42/291 | 21/286 | 2.26 (0.91, 5.60) | 44

  PMID 35579691 · one of two readings recorded this

• diarrhoea

  increases

  Tirzepatide 15 mg | Placebo | 71/350 | 23/312 | 3.31 (1.40, 7.85) | 52

  PMID 35579691 · one of two readings recorded this

• diarrhoea

  no effect

  Tirzepatide 5 mg | Placebo | 39/292 | 21/286 | 2.09 (0.77, 5.69) | 51

  PMID 35579691 · one of two readings recorded this

• diarrhoea

  increases

  Basal insulin | 125/688 | 58/1360 | 5.23 (3.74, 7.33) | 0

  PMID 35579691 · one of two readings recorded this

• diarrhoea

  increases

  GLP-1 RAs | 89/520 | 63/523 | 1.51 (1.07, 2.15) | 0

  PMID 35579691 · one of two readings recorded this

• diarrhoea

  increases

  Basal insulin | 130/697 | 58/1360 | 5.59 (4.01, 7.79) | 0

  PMID 35579691 · one of two readings recorded this

• diarrhoea

  no effect

  GLP-1 RAs | 82/523 | 63/523 | 1.48 (0.84, 2.64) | 39

  PMID 35579691 · one of two readings recorded this

• diarrhoea

  increases

  Basal insulin | 96/687 | 58/1360 | 3.52 (2.46, 5.05) | 0

  PMID 35579691 · one of two readings recorded this

• diarrhoea

  no effect

  GLP-1 RAs | 75/525 | 63/523 | 1.22 (0.85, 1.74) | 0

  PMID 35579691 · one of two readings recorded this

• HbA1c change

  decreases

  reductions in HbA1c levels ranged between 17.71 mmol/mol (1.62%) with tirzepatide 5 mg and 22.35 mmol/mol (2.06%) with tirzepatide 15 mg

  PMID 35579691 · one of two readings recorded this

• HbA1c change

  decreases

  reductions in HbA1c levels ranged between 17.71 mmol/mol (1.62%) with tirzepatide 5 mg and 22.35 mmol/mol (2.06%) with tirzepatide 15 mg

  PMID 35579691 · one of two readings recorded this

• HbA1c change

  decreases

  tirzepatide 5, 10 and 15 mg reduced HbA1c levels by 3.22 mmol/mol (0.29%), 7.11 mmol/mol (0.65%) and 10.06 mmol/mol (0.92%), respectively

  PMID 35579691 · one of two readings recorded this

• HbA1c change

  decreases

  7.66 mmol/mol [0.70%] with tirzepatide 5 mg and 12.02 mmol/mol [1.09%] with tirzepatide 15 mg

  PMID 35579691 · one of two readings recorded this

• HbA1c change

  decreases

  tirzepatide 5, 10 and 15 mg reduced HbA1c levels by 3.22 mmol/mol (0.29%), 7.11 mmol/mol (0.65%) and 10.06 mmol/mol (0.92%), respectively

  PMID 35579691 · one of two readings recorded this

• HbA1c change

  decreases

  7.66 mmol/mol [0.70%] with tirzepatide 5 mg and 12.02 mmol/mol [1.09%] with tirzepatide 15 mg

  PMID 35579691 · one of two readings recorded this

• HbA1c change

  decreases

  tirzepatide 5, 10 and 15 mg reduced HbA1c levels by 3.22 mmol/mol (0.29%), 7.11 mmol/mol (0.65%) and 10.06 mmol/mol (0.92%), respectively

  PMID 35579691 · one of two readings recorded this

• mean basal insulin dose at study endpoint

  the mean basal insulin dose at the study endpoint (week 52) was 48.8 U with insulin degludec in the SURPASS-3 trial and 43.5 U with insulin glargine in the SURPASS-4 trial

  PMID 35579691 · one of two readings recorded this

• mean basal insulin dose at study endpoint

  the mean basal insulin dose at the study endpoint (week 52) was 48.8 U with insulin degludec in the SURPASS-3 trial and 43.5 U with insulin glargine in the SURPASS-4 trial

  PMID 35579691 · one of two readings recorded this

• nausea, vomiting and diarrhoea incidence by dose, odds ratio

  increases, nausea 15 mg OR 5.60, 95% CI 3.12, 10.06

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

  Compared with placebo, nausea was more frequent with all tirzepatide doses, especially 15 mg (OR 5.60 [95% CI 3.12, 10.06], I2 0%) (Table 2).

  PMID 35579691 · one of two readings recorded this

• nausea

  increases

  Tirzepatide 10 mg | Placebo | 45/291 | 13/286 | 3.66 (1.91, 7.02) | 0

  PMID 35579691 · one of two readings recorded this

• nausea

  increases

  Tirzepatide 15 mg | Placebo | 82/350 | 15/312 | 5.60 (3.12, 10.06) | 0

  PMID 35579691 · one of two readings recorded this

• nausea

  increases

  Tirzepatide 5 mg | Placebo | 38/292 | 13/286 | 3.02 (1.56, 5.86) | 0

  PMID 35579691 · one of two readings recorded this

• nausea

  increases

  Basal insulin | 134/688 | 29/1360 | 10.93 (5.39, 22.15) | 54

  PMID 35579691 · one of two readings recorded this

• nausea

  no effect

  GLP-1 RAs | 101/520 | 100/523 | 1.00 (0.69, 1.45) | 11

  PMID 35579691 · one of two readings recorded this

• nausea

  increases

  Basal insulin | 161/697 | 29/1360 | 13.60 (8.93, 20.72) | 0

  PMID 35579691 · one of two readings recorded this

• nausea

  no effect

  GLP-1 RAs | 125/523 | 100/523 | 1.34 (0.99, 1.80) | 0

  PMID 35579691 · one of two readings recorded this

• nausea

  increases

  Basal insulin | 80/687 | 29/1360 | 6.18 (3.93, 9.73) | 0

  PMID 35579691 · one of two readings recorded this

• nausea

  no effect

  GLP-1 RAs | 93/525 | 100/523 | 0.91 (0.65, 1.26) | 3

  PMID 35579691 · one of two readings recorded this

• proportion reaching HbA1c targets

  increases

  All tirzepatide doses were superior to placebo in terms of achieving the HbA1c target of <53 mmol/mol (<7.0%), ≤48 mmol/mol (≤6.5%) or <39 mmol/mol (<5.7%)

  PMID 35579691 · one of two readings recorded this

• serious adverse events

  no effect

  Incidence of serious adverse events did not differ between any of the tirzepatide doses and any comparator

  PMID 35579691 · one of two readings recorded this

• treatment discontinuation due to adverse events

  increases

  OR 2.39 [95% CI 1.02, 5.59], I2 0%

  PMID 35579691 · one of two readings recorded this

• treatment discontinuation due to adverse events

  increases

  OR 3.64 [95% CI 1.51, 8.78], I2 13%

  PMID 35579691 · one of two readings recorded this

• treatment discontinuation due to adverse events

  no effect

  OR 1.99 [95% CI 0.83, 4.77], I2 0%

  PMID 35579691 · one of two readings recorded this

• treatment discontinuation due to adverse events

  increases

  OR 2.29 [95% CI 1.39, 3.75], I2 0%

  PMID 35579691 · one of two readings recorded this

• vomiting

  increases

  Tirzepatide 10 mg | Placebo | 19/291 | 6/286 | 2.98 (1.13, 7.80) | 0

  PMID 35579691 · one of two readings recorded this

• vomiting

  increases

  Tirzepatide 15 mg | Placebo | 44/350 | 7/312 | 5.50 (2.40, 12.59) | 0

  PMID 35579691 · one of two readings recorded this

• vomiting

  no effect

  Tirzepatide 5 mg | Placebo | 15/292 | 6/286 | 2.51 (0.95, 6.61) | 0

  PMID 35579691 · one of two readings recorded this

• vomiting

  increases

  Basal insulin | 61/688 | 20/1360 | 6.34 (3.69, 10.89) | 0

  PMID 35579691 · one of two readings recorded this

• vomiting

  no effect

  GLP-1 RAs | 48/520 | 44/523 | 1.11 (0.72, 1.70) | 0

  PMID 35579691 · one of two readings recorded this

• vomiting

  increases

  Basal insulin | 65/697 | 20/1360 | 6.66 (3.90, 11.37) | 0

  PMID 35579691 · one of two readings recorded this

• vomiting

  no effect

  GLP-1 RAs | 60/523 | 44/523 | 1.81 (0.65, 5.08) | 68

  PMID 35579691 · one of two readings recorded this

• vomiting

  increases

  Basal insulin | 37/687 | 20/1360 | 3.72 (2.06, 6.72) | 0

  PMID 35579691 · one of two readings recorded this

• vomiting

  no effect

  GLP-1 RAs | 31/525 | 44/523 | 0.68 (0.42, 1.10) | 0

  PMID 35579691 · one of two readings recorded this

• adverse events leading to study drug discontinuation

  increases

  the incidence of any adverse events and adverse events leading to study drug discontinuation was higher in the tirzepatide group, but the incidence of serious adverse events and hypoglycaemia was lower

  PMID 37141329 · one of two readings recorded this

• any adverse events

  increases

  the incidence of any adverse events and adverse events leading to study drug discontinuation was higher in the tirzepatide group, but the incidence of serious adverse events and hypoglycaemia was lower

  PMID 37141329 · one of two readings recorded this

• body weight change at 5 mg, 10 mg and 15 mg doses

  decreases

  the body weight of patients was significantly reduced in three tirzepatide doses (5 mg, 10 mg, and 15 mg) when compared with those of the placebo/GLP-1 RA/insulin

  PMID 37141329 · one of two readings recorded this

• body weight change

  decreases

  by -9.81 kg (95% CI (-12.09, -7.52)

  PMID 37141329 · one of two readings recorded this

• body weight change

  decreases

  GLP-1 RAs by -1.05 kg (95% CI (-1.48, -0.63)

  PMID 37141329 · one of two readings recorded this

• gastrointestinal adverse events (diarrhea, nausea, vomiting, decreased appetite)

  increases

  the gastrointestinal adverse events (including diarrhea, nausea, vomiting and decreased appetite) of tirzepatide were higher than those of placebo/basal insulin, but similar to GLP-1 RAs

  PMID 37141329 · one of two readings recorded this

• gastrointestinal adverse events (diarrhea, nausea, vomiting, decreased appetite)

  no effect

  the gastrointestinal adverse events (including diarrhea, nausea, vomiting and decreased appetite) of tirzepatide were higher than those of placebo/basal insulin, but similar to GLP-1 RAs

  PMID 37141329 · one of two readings recorded this

• hypoglycaemia

  decreases

  the incidence of any adverse events and adverse events leading to study drug discontinuation was higher in the tirzepatide group, but the incidence of serious adverse events and hypoglycaemia was lower

  PMID 37141329 · one of two readings recorded this

• serious adverse events

  decreases

  the incidence of any adverse events and adverse events leading to study drug discontinuation was higher in the tirzepatide group, but the incidence of serious adverse events and hypoglycaemia was lower

  PMID 37141329 · one of two readings recorded this

• abdominal pain and abdominal distension

  no effect, p = 0.05

  while abdominal pain and abdominal distension were comparable (P > .05)

  PMID 37904345 · one of two readings recorded this

• decreased appetite

  increases

  Compared with GLP-1 RA, decreased appetite was significantly higher with TZP 5 mg

  PMID 37904345 · one of two readings recorded this

• dyspepsia

  increases, p = 0.05

  dyspepsia was significantly increased with TZP 15 mg (P < .05)

  PMID 37904345 · one of two readings recorded this

• gastrointestinal adverse events (total GI AEs, nausea, decreased appetite, constipation, vomiting, abdominal pain, abdominal distension) vs placebo, by dose

  increases, P < .05 for total GI AEs, nausea, decreased appetite, constipation and vomiting in all dose groups

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

  Meta-analysis showed that compared with placebo, total GI AEs, nausea, decreased appetite, constipation and vomiting were significantly higher in all dose groups of TZP (P < .05), while abdominal pain and abdominal distension were comparable (P > .05).

  PMID 37904345 · one of two readings recorded this

• nausea, diarrhea and decreased appetite incidence by dose

  increases

  Nausea, diarrhea and decreased appetite are very common GI AEs of TZP, and the incidence is positively correlated with dose

  PMID 37904345 · one of two readings recorded this

• nausea, diarrhea, vomiting and decreased appetite

  increases, p = 0.05

  Compared with insulin, nausea, diarrhea, vomiting and decreased appetite were significantly increased in all doses of TZP (P < .05)

  PMID 37904345 · one of two readings recorded this

• overall GI AEs

  no effect

  The GI AEs of TZP were significantly higher than those of placebo and insulin, but comparable to GLP-1 RA

  PMID 37904345 · one of two readings recorded this

• total gastrointestinal adverse events, nausea, decreased appetite, constipation and vomiting in type 2 diabetes, tirzepatide versus placebo, insulin and GLP-1 RA

  increases

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

  Meta-analysis showed that compared with placebo, total GI AEs, nausea, decreased appetite, constipation and vomiting were significantly higher in all dose groups of TZP (P < .05), while abdominal pain and abdominal distension were comparable (P > .05).

  PMID 37904345 · one of two readings recorded this

• total GI AEs, decreased appetite and diarrhea

  increases, p = 0.05

  total GI AEs, decreased appetite and diarrhea were significantly higher with TZP 10 mg (P < .05)

  PMID 37904345 · one of two readings recorded this

• total GI AEs, nausea, decreased appetite, constipation and vomiting

  increases, p = 0.05

  compared with placebo, total GI AEs, nausea, decreased appetite, constipation and vomiting were significantly higher in all dose groups of TZP (P < .05)

  PMID 37904345 · one of two readings recorded this

• biliary diseases risk

  no effect

  but not with the risk of cholelithiasis, cholecystitis or biliary diseases

  PMID 37908750 · one of two readings recorded this

• cholecystitis risk

  no effect

  but not with the risk of cholelithiasis, cholecystitis or biliary diseases

  PMID 37908750 · one of two readings recorded this

• cholelithiasis risk

  no effect

  but not with the risk of cholelithiasis, cholecystitis or biliary diseases

  PMID 37908750 · one of two readings recorded this

• composite of gallbladder or biliary disease

  increases, p = 0.558

  (RR 1.97, [95% CI] 1.14 to 3.42; I2 = 0.0%, p = 0.558)

  PMID 37908750 · one of two readings recorded this

• composite of gallbladder or biliary diseases, cholelithiasis, cholecystitis and pancreatitis, tirzepatide versus placebo, basal insulin or selective GLP1-RA

  increases, RR 1.97, 95% CI 1.14 to 3.42 versus placebo or basal insulin

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

  For gallbladder or biliary disease, the composite of gallbladder or biliary disease was significantly associated with tirzepatide compared with placebo or basal insulin (RR 1.97, [95% CI] 1.14 to 3.42; I2 = 0.0%, p = 0.558), but not with the risk of cholelithiasis, cholecystitis or biliary diseases.

  PMID 37908750 · one of two readings recorded this

• composite of gallbladder or biliary diseases, pooled risk ratio vs placebo or basal insulin; pancreatitis, cholecystitis, cholelithiasis

  increases, RR 1.97, 95% CI 1.14 to 3.42

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

  For gallbladder or biliary disease, the composite of gallbladder or biliary disease was significantly associated with tirzepatide compared with placebo or basal insulin (RR 1.97, [95% CI] 1.14 to 3.42; I2 = 0.0%, p = 0.558), but not with the risk of cholelithiasis, cholecystitis or biliary diseases.

  PMID 37908750 · one of two readings recorded this

• pancreatitis risk

  no effect, p = 0.436

  (RR 1.46, [95% CI] 0.59 to 3.61; I2 = 0.0%, p = 0.436)

  PMID 37908750 · one of two readings recorded this

• body mass index

  decreases, p = 0.00001

  [MD = -3.99, 95% CI (-3.69, -2.45), p < 0.00001]

  PMID 38356942 · one of two readings recorded this

• body mass index

  decreases, p = 0.00001

  [MD = -1.71, 95% CI (-2.46, -0.95), p < 0.00001]

  PMID 38356942 · one of two readings recorded this

• waist circumference

  decreases, p = 0.00001

  [MD = -7.71, 95% CI (-10.17, -5.25), p < 0.00001]

  PMID 38356942 · one of two readings recorded this

• waist circumference

  decreases, p = 0.00001

  [MD = -4.08, 95% CI (-5.77, -2.39), p < 0.00001]

  PMID 38356942 · one of two readings recorded this

• BMI (body mass index), waist circumference and body weight, mean difference vs GLP-1 RA, placebo and insulin groups

  decreases, BMI MD = -1.71, 95% CI (-2.46, -0.95); MD = -3.99; MD = -4.02, 95% CI (-4.72, -3.31)

  Not recorded as a finding: the comparison was against another active treatment

  Meta analysis results showed that compared with the glucagon like peptide-1 receptor agonist (GLP-1 RAs), placebo and insulin groups, tirzepatide could significantly reduce the BMI (body mass index) of patients [MD = -1.71, 95% CI (-2.46, -0.95), p < 0.00001], [MD = -3.99, 95% CI (-3.69, -2.45), p < 0.00001], [MD = -4.02, 95% CI (-4.72, -3.31), p < 00.00001].

  PMID 38356942 · one of two readings recorded this

• body mass index, waist circumference and body weight in obesity, tirzepatide versus GLP-1 RAs, placebo and insulin

  decreases, BMI MD -1.71, -3.99, -4.02 (order of comparators not stated per estimate)

  Not recorded as a finding: the comparison was against another active treatment

  Meta analysis results showed that compared with the glucagon like peptide-1 receptor agonist (GLP-1 RAs), placebo and insulin groups, tirzepatide could significantly reduce the BMI (body mass index) of patients [MD = -1.71, 95% CI (-2.46, -0.95), p < 0.00001], [MD = -3.99, 95% CI (-3.69, -2.45), p < 0.00001], [MD = -4.02, 95% CI (-4.72, -3.31), p < 00.00001].

  PMID 38356942 · one of two readings recorded this

• body weight

  decreases, p = 0.001

  [MD = -5.65, 95% CI (-7.47, -3.82), p < 0.001]

  PMID 38356942 · one of two readings recorded this

• body weight

  decreases, p = 0.001

  [MD = -10.06, 95% CI (-12.86, -7.25), p < 0.001]

  PMID 38356942 · one of two readings recorded this

• body weight

  decreases, p = 0.001

  [MD = -10.63, 95% CI (-12.42, -8.84), p < 0.001]

  PMID 38356942 · one of two readings recorded this

• hypoglycemia (<70 mg/dL)

  decreases, p = 0.001

  [RR = 0.46, 95% CI (0.36, 0.58), p < 0.001]

  PMID 38356942 · one of two readings recorded this

• weight loss of at least 20%

  increases, p = 0.00001

  [RR = 30.43, 95% CI (19.56, 47.33), p < 0.00001]

  PMID 38356942 · one of two readings recorded this

• weight loss of at least 25%

  increases, p = 0.00001

  [RR = 37.25, 95% CI (26.03, 53.30), p < 0.00001]

  PMID 38356942 · one of two readings recorded this

• all-cause mortality

  decreases, p = 0.01

  all-cause mortality (OR: 0.88; 95% CI: 0.82-0.96; p < 0.01; I2 = 21%)

  PMID 38400569 · one of two readings recorded this

• cardiovascular mortality

  decreases, p = 0.01

  cardiovascular-mortality (OR: 0.88; 95% CI: 0.80-0.96; p < 0.01; I2 = 14%)

  PMID 38400569 · one of two readings recorded this

• fatal stroke

  no effect, p = 0.105

  fatal stroke and GLP-1RAs was uncovered (OR: 0.80; 95% CI: 0.61-1.05; p = 0.105; I2 = 0%)

  PMID 38400569 · one of two readings recorded this

• hemorrhagic stroke

  no effect, p = 0.792

  hemorrhagic stroke (OR: 0.92; 95% CI: 0.51-1.66; p = 0.792; I2 = 0%)

  PMID 38400569 · one of two readings recorded this

• ischemic stroke

  decreases, p = 0.01

  GLP-1 RAs prevented ischemic stroke (OR: 0.74; 95% CI: 0.61-0.91; p < 0.01; I2 = 0%)

  PMID 38400569 · one of two readings recorded this

• major adverse cardiovascular events, all-cause mortality and cardiovascular mortality, pooled across GLP-1 receptor agonists and tirzepatide (4 of 13 trials) vs placebo

  decreases, all-cause mortality OR 0.88; 95% CI 0.82-0.96

  Not recorded as a finding: another reason, stated per paper

  Compared to placebo, GLP-1RAs or GIP/GLP-1 RAs reduced MACE (OR: 0.87; 95% CI: 0.81-0.94; p < 0.01; I2 = 37%), all-cause mortality (OR: 0.88; 95% CI: 0.82-0.96; p < 0.01; I2 = 21%) and cardiovascular-mortality (OR: 0.88; 95% CI: 0.80-0.96; p < 0.01; I2 = 14%), without differences between GLP-1 versus GIP/GLP-1 RAs.

  PMID 38400569 · one of two readings recorded this

• major adverse cardiovascular events (MACE)

  decreases, p = 0.01

  reduced MACE (OR: 0.87; 95% CI: 0.81-0.94; p < 0.01; I2 = 37%)

  PMID 38400569 · one of two readings recorded this

• nonfatal stroke

  decreases, p = 0.01

  nonfatal stroke (OR: 0.85; 95% CI: 0.76-0.94; p < 0.01; I2 = 0%)

  PMID 38400569 · one of two readings recorded this

• stroke

  decreases, p = 0.01

  GLP-1 RAs reduced the odds of stroke (OR: 0.84; 95% CI: 0.76-0.93; p < 0.01; I2 = 0%)

  PMID 38400569 · one of two readings recorded this

• expression of markers of fibrosis, hypertrophy and cell death under high glucose

  decreases, p = 0.05

  (p < 0.05 for all investigated markers)

  PMID 38555463 · one of two readings recorded this

• major adverse cardiovascular events (MACE) occurrence, pooled hazard ratio from major randomized clinical trials; also gene and protein markers of fibrosis, hypertrophy and cell death in human AC16 cardiac cells under high glucose

  decreases, HR 0.59, 95% CI 0.40-0.79

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

  Meta-analysis showed a reduced risk for MACE events by TZT therapy (HR was 0.59 (95% CI 0.40-0.79, Heterogeneity: r2 = 0.01, I2 = 23.45%, H2 = 1.31).

  PMID 38555463 · one of two readings recorded this

• major adverse cardiovascular events (MACE) occurrence, pooled hazard ratio from randomised clinical trials

  decreases, HR 0.59 (95% CI 0.40-0.79)

  Not recorded as a finding: the supporting sentence never names the compound

  Meta-analysis showed a reduced risk for MACE events by TZT therapy (HR was 0.59 (95% CI 0.40-0.79, Heterogeneity: r2 = 0.01, I2 = 23.45%, H2 = 1.31).

  PMID 38555463 · one of two readings recorded this

• major adverse cardiovascular events (MACE)

  decreases

  reduced risk for MACE events by TZT therapy (HR was 0.59 (95% CI 0.40-0.79

  PMID 38555463 · one of two readings recorded this

• adverse events rate

  no effect, p = 0.07

  77.8 vs 71.2% (p = 0.07, moderate certainty) for the 10 mg dose

  PMID 38850440 · one of two readings recorded this

• adverse events rate

  increases, p = 0.03

  76.4 vs 71.0% (p = 0.03, moderate certainty) for the 15 mg dose

  PMID 38850440 · one of two readings recorded this

• adverse events rate

  increases, p = 0.0001

  77.9 vs 69.6% (p < 0.0001, high certainty) for the 5 mg dose

  PMID 38850440 · one of two readings recorded this

• body mass index change vs placebo

  decreases, p = 0.00001

  10 mg dose (−3.4 kg/m2, 95%CI [−3.7, −3.1], p < 0.00001, high certainty)

  PMID 38850440 · one of two readings recorded this

• body mass index change vs placebo

  decreases, p = 0.00001

  15 mg dose (−4.0 kg/m2, 95%CI [−4.5, −3.5], p < 0.00001, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• body mass index change vs placebo

  decreases, p = 0.00001

  5 mg dose (−2.6 kg/m2, 95%CI [−3.4, −1.7], p < 0.00001, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• body weight, absolute change vs placebo

  decreases, p = 0.0002

  −11.0 kg (95%CI [−16.9, −5.2], p = 0.0002, moderate certainty) for 10 mg

  PMID 38850440 · one of two readings recorded this

• body weight, absolute change vs placebo

  decreases, p = 0.00001

  −11.5 kg (95%CI [−16.2, −6.7], p < 0.00001, moderate certainty) for 15 mg

  PMID 38850440 · one of two readings recorded this

• body weight, absolute change vs placebo

  decreases, p = 0.0001

  −7.5 kg (95%CI [−10.9, −4.1], p < 0.0001, moderate certainty) for 5 mg

  PMID 38850440 · one of two readings recorded this

• body weight, mean percentage change vs placebo

  decreases, p = 0.00001

  10 mg (−10.79, 95%CI [−13.86, −7.71], p < 0.00001, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• body weight, mean percentage change vs placebo

  decreases, p = 0.00001

  15 mg (−11.83, 95%CI [−14.52, −9.14], p < 0.00001, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• body weight, mean percentage change vs placebo

  decreases, p = 0.00001

  5 mg (−8.07, 95%CI [−11.01, −5.13], p < 0.00001, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• constipation

  increases, p = 0.00001

  10 mg: 2.83, P <0.00001, moderate certainty

  PMID 38850440 · one of two readings recorded this

• constipation

  increases, p = 0.00001

  15 mg: 2.29, P <0.00001, moderate certainty

  PMID 38850440 · one of two readings recorded this

• constipation

  increases, p = 0.00001

  constipation(5 mg: 3.04, P <0.00001, moderate certainty

  PMID 38850440 · one of two readings recorded this

• decreased appetite

  increases, p = 0.00001

  10 mg: 4.17, P <0.00001, moderate certainty

  PMID 38850440 · one of two readings recorded this

• decreased appetite

  increases, p = 0.00001

  15 mg: 3.60, P <0.00001, moderate certainty

  PMID 38850440 · one of two readings recorded this

• decreased appetite

  increases, p = 0.00001

  decreased appetite(5 mg: 3.21, P <0.00001, moderate certainty

  PMID 38850440 · one of two readings recorded this

• diarrhea

  increases, p = 0.00001

  10 mg: 2.29, P <0.00001, moderate certainty;15 mg: 2.38, P <0.00001, low certainty

  PMID 38850440 · one of two readings recorded this

• diarrhea

  increases, p = 0.00001

  15 mg: 2.38, P <0.00001, low certainty

  PMID 38850440 · one of two readings recorded this

• diarrhea

  increases, p = 0.007

  diarrhea (5 mg: 2.04, p = 0.007, low certainty

  PMID 38850440 · one of two readings recorded this

• diastolic blood pressure change vs placebo

  decreases, p = 0.005

  −2.25 mmHg (95% CI: −3.80, −0.69; P = 0.005, low certainty) for the 10 mg dose

  PMID 38850440 · one of two readings recorded this

• diastolic blood pressure change vs placebo

  decreases, p = 0.00001

  −2.86 mmHg (95% CI: −3.46, −2.27; P < 0.00001, moderate certainty) for the 15 mg dose

  PMID 38850440 · one of two readings recorded this

• diastolic blood pressure change vs placebo

  no effect, p = 0.11

  −1.9 mmHg (95% CI: −4.24, 0.44; P = 0.11, low certainty) for the 5 mg dose

  PMID 38850440 · one of two readings recorded this

• diastolic blood pressure, MD per dose

  Not recorded as a finding: sentence says all three doses reduced DBP but the 5 mg interval crosses zero (P = 0.11); the conclusion contradicts its own figures

  Compared to the placebo, all three tirzepatide doses resulted in a reduction in DBP.

  PMID 38850440 · one of two readings recorded this

• discontinuation due to adverse events (DAEs) per dose

  increases, 15 mg 7.3 vs 3.2%, p = 0.002

  Not recorded as a finding: object span is the abbreviation DAEs, defined only in Methods, so the quote is not self-supporting for the withdrawal node

  Similarly, a higher proportion of DAEs was observed in the tirzepatide groups compared to placebo, as shown in Figure S12 and Table S3 (5 mg:4.7 vs 2.7%, p = 0.03, moderate certainty;10 mg:6.1 vs 3.0%, p = 0.004, moderate certainty;15 mg:7.3 vs 3.2%, p = 0.002, moderate certainty).

  PMID 38850440 · one of two readings recorded this

• discontinuation due to adverse events

  increases, p = 0.004

  10 mg:6.1 vs 3.0%, p = 0.004, moderate certainty

  PMID 38850440 · one of two readings recorded this

• discontinuation due to adverse events

  increases, p = 0.002

  15 mg:7.3 vs 3.2%, p = 0.002, moderate certainty

  PMID 38850440 · one of two readings recorded this

• discontinuation due to adverse events

  increases, p = 0.03

  5 mg:4.7 vs 2.7%, p = 0.03, moderate certainty

  PMID 38850440 · one of two readings recorded this

• dyspepsia

  increases, p = 0.00001

  10 mg: 2.44, P <0.00001, moderate certainty

  PMID 38850440 · one of two readings recorded this

• dyspepsia

  increases, p = 0.00001

  15 mg: 2.45, P <0.00001, moderate certainty

  PMID 38850440 · one of two readings recorded this

• dyspepsia

  increases, p = 0.0001

  dyspepsia(5 mg: 2.28, P <0.0001, moderate certainty

  PMID 38850440 · one of two readings recorded this

• fasting plasma glucose change vs placebo

  decreases, p = 0.0001

  10 mg dose (−2.25 mmol/L, 95%CI [−3.36, −1.14], p < 0.0001, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• fasting plasma glucose change vs placebo

  decreases, p = 0.00001

  15 mg dose (−2.44 mmol/L, 95%CI [−3.41, −1.47], p < 0.00001, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• fasting plasma glucose change vs placebo

  decreases, p = 0.003

  5 mg dose (−1.89 mmol/L, 95%CI [−3.15, −0.64], p = 0.003, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• HbA1c change vs placebo

  decreases, p = 0.0002

  10 mg dose (−1.45%, 95%CI [−2.21, −0.69], p = 0.0002, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• HbA1c change vs placebo

  decreases, p = 0.00001

  15 mg dose (−1.69%, 95%CI [−2.39, −0.99], p < 0.00001, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• HbA1c change vs placebo

  decreases, p = 0.004

  5 mg dose (−1.28%, 95%CI [−2.15, −0.41], p = 0.004, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• HDL cholesterol change vs placebo

  increases, p = 0.008

  0.06 mmol/L (95% CI:0.02, 0.10; P = 0.008, moderate certainty) for 10 mg

  PMID 38850440 · one of two readings recorded this

• HDL cholesterol change vs placebo

  increases, p = 0.0001

  0.08 mmol/L (95% CI:0.04, 0.12; P < 0.0001, moderate certainty) for 15 mg

  PMID 38850440 · one of two readings recorded this

• HDL cholesterol change vs placebo

  no effect, p = 0.07

  0.05 mmol/L (95% CI: −0.00, 0.10; P = 0.07, moderate certainty) for 5 mg

  PMID 38850440 · one of two readings recorded this

• hypoglycemia

  no effect, p = 0.11

  10 mg: 13.1 vs 10.0%, p = 0.11, low certainty

  PMID 38850440 · one of two readings recorded this

• hypoglycemia

  no effect, p = 0.06

  15 mg: 12.1 vs 9.5%, p = 0.06, low certainty

  PMID 38850440 · one of two readings recorded this

• hypoglycemia

  no effect, p = 0.17

  5 mg:11.7 vs 10.0%, p = 0.17, low certainty

  PMID 38850440 · one of two readings recorded this

• LDL cholesterol change vs placebo

  decreases, p = 0.0001

  −0.19 mmol/L(95% CI:−0.27, −0.10;P <0.0001, high certainty) for 10 mg

  PMID 38850440 · one of two readings recorded this

• LDL cholesterol change vs placebo

  decreases, p = 0.0001

  −0.24 mmol/L(95% CI:−0.36, −0.13;P < 0.0001, moderate certainty) for 15 mg

  PMID 38850440 · one of two readings recorded this

• LDL cholesterol change vs placebo

  decreases, p = 0.00001

  −0.15 mmol/L(95% CI:−0.21,−0.09; P <0.00001, high certainty) for 5 mg

  PMID 38850440 · one of two readings recorded this

• nausea

  increases, p = 0.00001

  10 mg:3.42, P <0.00001, moderate certainty

  PMID 38850440 · one of two readings recorded this

• nausea

  increases, p = 0.00001

  15 mg: 3.24, P <0.00001, low certainty

  PMID 38850440 · one of two readings recorded this

• nausea

  increases, p = 0.00001

  nausea (5 mg: 2.63, P <0.00001, moderate certainty

  PMID 38850440 · one of two readings recorded this

• proportion achieving weight loss of at least 10%

  increases, p = 0.00001

  64.9% for 10 mg (vs. 12.3%, p < 0.00001, low certainty)

  PMID 38850440 · one of two readings recorded this

• proportion achieving weight loss of at least 10%

  increases, p = 0.00001

  69.2% for 15 mg (vs. 12.3%, p < 0.00001, low certainty)

  PMID 38850440 · one of two readings recorded this

• proportion achieving weight loss of at least 10%

  increases, p = 0.001

  54.4% for 5 mg (vs. 13.3%, p = 0.001, low certainty)

  PMID 38850440 · one of two readings recorded this

• proportion achieving weight loss of at least 15%

  increases, p = 0.00001

  49.1% for 10 mg (vs. 5.2%, p < 0.00001, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• proportion achieving weight loss of at least 15%

  increases, p = 0.00001

  54.1% for 15 mg (vs. 5.2%, p < 0.00001, low certainty)

  PMID 38850440 · one of two readings recorded this

• proportion achieving weight loss of at least 15%

  increases, p = 0.00001

  35.7% for 5 mg (vs. 6.1%, p < 0.00001, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• proportion achieving weight loss of at least 20%

  increases, p = 0.00001

  10 mg (40.7 vs 2.4%, p < 0.00001, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• proportion achieving weight loss of at least 20%

  increases, p = 0.00001

  15 mg (48.1 vs 2.4%, p < 0.00001, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• proportion achieving weight loss of at least 20%

  increases, p = 0.00001

  5 mg (30 vs 3.1%, p < 0.00001, high certainty)

  PMID 38850440 · one of two readings recorded this

• proportion achieving weight loss of at least 25%

  increases, p = 0.00001

  10 mg (24.6 vs 1.1%, p < 0.00001, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• proportion achieving weight loss of at least 25%

  increases, p = 0.00001

  15 mg (29.3 vs 1.1%, p < 0.00001, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• proportion achieving weight loss of at least 25%

  increases, p = 0.00001

  5 mg (15.2 vs 1.6%, p < 0.00001, high certainty)

  PMID 38850440 · one of two readings recorded this

• proportion achieving weight loss of at least 5%

  increases, p = 0.00001

  81.6% for 10 mg (vs. 27.9%, p < 0.00001, low certainty)

  PMID 38850440 · one of two readings recorded this

• proportion achieving weight loss of at least 5%

  increases, p = 0.00001

  84.3% for 15 mg (vs. 27.9%, p < 0.00001, low certainty)

  PMID 38850440 · one of two readings recorded this

• proportion achieving weight loss of at least 5%

  increases, p = 0.0001

  75.8% for 5 mg (vs. 26.4%, p < 0.0001, low certainty)

  PMID 38850440 · one of two readings recorded this

• serious adverse events

  no effect, p = 0.92

  10 mg: 6.5 vs 6.6%, p = 0.92, moderate certainty

  PMID 38850440 · one of two readings recorded this

• serious adverse events

  no effect, p = 0.36

  15 mg: 5.4 vs 6.5%, p = 0.36, moderate certainty

  PMID 38850440 · one of two readings recorded this

• serious adverse events

  no effect, p = 0.76

  5 mg: 6.0 vs 6.4%, p = 0.76, moderate certainty

  PMID 38850440 · one of two readings recorded this

• systolic blood pressure change vs placebo

  decreases, p = 0.00001

  10 mg dose (−5.3 mmHg, 95%CI [−6.89, −3.72], p<0.00001, low certainty)

  PMID 38850440 · one of two readings recorded this

• systolic blood pressure change vs placebo

  decreases, p = 0.00001

  15 mg dose (−6.4 mmHg, 95%CI [−8.13, −4.68], p<0.00001, low certainty)

  PMID 38850440 · one of two readings recorded this

• systolic blood pressure change vs placebo

  decreases, p = 0.00001

  5 mg dose (−4.86 mmHg, 95%CI [−6.34, −3.37], p<0.00001, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• total cholesterol change vs placebo

  decreases, p = 0.00001

  −0.30 mmol/L(95% CI:−0.40, −0.20;P <0.00001, high certainty) for 10 mg

  PMID 38850440 · one of two readings recorded this

• total cholesterol change vs placebo

  decreases, p = 0.00001

  −0.37 mmol/L(95% CI:−0.49, −0.24; P < 0.00001, moderate certainty) for 15 mg

  PMID 38850440 · one of two readings recorded this

• total cholesterol change vs placebo

  decreases, p = 0.00001

  −0.25 mmol/L(95% CI:−0.34, −0.15; P <0.00001, high certainty) for 5 mg

  PMID 38850440 · one of two readings recorded this

• triglycerides change vs placebo

  decreases, p = 0.00001

  −0.37 mmol/L(95% CI:−0.50, −0.25;P < 0.00001, low certainty) for 10 mg

  PMID 38850440 · one of two readings recorded this

• triglycerides change vs placebo

  decreases, p = 0.00001

  −0.43 mmol/L(95% CI:−0.54, −0.32; P < 0.00001, low certainty) for 15 mg

  PMID 38850440 · one of two readings recorded this

• triglycerides change vs placebo

  decreases, p = 0.0001

  −0.31 mmol/L(95% CI:−0.46, −0.17; P < 0.0001, low certainty) for 5 mg

  PMID 38850440 · one of two readings recorded this

• VLDL cholesterol change vs placebo

  decreases, p = 0.00001

  −0.19 mmol/L (95% CI: −0.26, −0.12; p < 0.00001, moderate certainty) for 10 mg

  PMID 38850440 · one of two readings recorded this

• VLDL cholesterol change vs placebo

  decreases, p = 0.00001

  −0.23 mmol/L(95% CI:−0.32, −0.13; P < 0.00001, moderate certainty) for 15 mg

  PMID 38850440 · one of two readings recorded this

• VLDL cholesterol change vs placebo

  decreases, p = 0.002

  −0.16 mmol/L(95% CI:−0.26, −0.06; P = 0.002, moderate certainty) for 5 mg

  PMID 38850440 · one of two readings recorded this

• vomiting

  increases, p = 0.00001

  10 mg: 4.34, P <0.00001, moderate certainty

  PMID 38850440 · one of two readings recorded this

• vomiting

  increases, p = 0.00001

  15 mg: 5.29, P <0.00001, moderate certainty

  PMID 38850440 · one of two readings recorded this

• vomiting

  increases, p = 0.00001

  vomiting(5 mg: 3.95, P <0.00001, moderate certainty

  PMID 38850440 · one of two readings recorded this

• waist circumference change vs placebo

  decreases, p = 0.00001

  10 mg (−8.8 cm, 95%CI [−11.9, −5.8], p < 0.00001, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• waist circumference change vs placebo

  decreases, p = 0.00001

  15 mg (−8.9 cm, 95%CI [−12.3, −5.5], p < 0.00001, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• waist circumference change vs placebo

  decreases, p = 0.00001

  5 mg (−6.8 cm, 95%CI [−9.3, −4.3], p < 0.00001, moderate certainty)

  PMID 38850440 · one of two readings recorded this

• body mass index

  decreases

  BMI (SMD - 2.13, 95% CI - 3.08 to - 1.18)

  PMID 39037553 · one of two readings recorded this

• waist circumference

  decreases

  WC (SMD - 0.91, 95% CI - 1.14 to - 0.69)

  PMID 39037553 · one of two readings recorded this

• blood pressure

  decreases

  Tirzepatide was associated with increased proportion of participants achieving weight loss targets, reduced body weight

  PMID 39037553 · one of two readings recorded this

• body weight

  decreases

  reduced body weight (SMD - 1.61, 95% CI - 2.20 to - 1.02)

  PMID 39037553 · one of two readings recorded this

• nausea, vomiting and diarrhoea incidence, odds ratio vs placebo

  increases, vomiting OR 8.35, 95% CI 5.19 to 13.45; diarrhea OR 3.57, 95% CI 2.80 to 4.57

  Not recorded as a finding: No outcome node for gastrointestinal adverse events

  However, the risk of adverse events such as nausea (OR 4.26, 95% CI 2.60 to 3.81), vomiting (OR 8.35, 95% CI 5.19 to 13.45), and diarrhea (OR 3.57, 95% CI 2.80 to 4.57) was significantly higher for tirzepatide versus placebo.

  PMID 39037553 · one of two readings recorded this

• nausea, vomiting, diarrhoea adverse events, odds ratio

  increases, vomiting OR 8.35, 95% CI 5.19 to 13.45

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

  However, the risk of adverse events such as nausea (OR 4.26, 95% CI 2.60 to 3.81), vomiting (OR 8.35, 95% CI 5.19 to 13.45), and diarrhea (OR 3.57, 95% CI 2.80 to 4.57) was significantly higher for tirzepatide versus placebo.

  PMID 39037553 · one of two readings recorded this

• proportion of participants achieving weight loss targets

  increases

  Tirzepatide was associated with increased proportion of participants achieving weight loss targets

  PMID 39037553 · one of two readings recorded this

The whole record — 617 rows