Certainty index

Moderate certainty

The true effect is likely to be close to the estimate, but there is a possibility that it is substantially different. Further research is likely to have an important impact on confidence in the estimate.

Graded outcomes

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Table 1. Outcomes and syntheses graded at moderate certainty, on this page.

Document	Type	Effect or conclusion as recorded
Semaglutide in hfpef	Evidence extract	KCCQ clinical summary score improvement of 7.8 points versus placebo at 52 weeks
Semaglutide in mash	Evidence extract	Resolution of steatohepatitis without worsening of fibrosis in 62.9 % versus 34.3 % with placebo at 72 weeks
Semaglutide in adolescent obesity	Evidence extract	−16.1 % BMI at 68 weeks versus +0.6 % with placebo
Semaglutide in peripheral arterial disease	Evidence extract	Maximum walking distance ratio to baseline 1.21 versus 1.08 with placebo at 52 weeks
Semaglutide in hypertension	Evidence extract	Systolic blood pressure −6.2 mmHg versus −1.1 mmHg with placebo (STEP 1)
Semaglutide, oral in cardiovascular	Evidence extract	MACE hazard ratio 0.79 (non-inferiority design) in PIONEER 6; 0.86 in the event-driven SOUL trial
Semaglutide, oral in obesity	Evidence extract	−15.1 % body weight with oral 50 mg at 68 weeks versus −2.4 % with placebo
Tirzepatide in hfpef	Evidence extract	Composite of cardiovascular death or worsening heart failure hazard ratio 0.62
Tirzepatide in cardiovascular	Evidence extract	MACE hazard ratio 0.92 versus dulaglutide 1.5 mg in an active-controlled non-inferiority design
Tirzepatide in prediabetes	Evidence extract	Progression to type 2 diabetes at 176 weeks reduced by 94 % in the prediabetes cohort
Retatrutide in obesity	Evidence extract	−24.2 % body weight at 48 weeks with 12 mg in the phase 2 trial versus −2.1 % with placebo
Retatrutide in type 2 diabetes	Evidence extract	−2.02 % HbA1c at 36 weeks with 12 mg versus −0.01 % with placebo; weight −16.9 %
Cagrilintide in obesity	Evidence extract	−10.8 % body weight at 26 weeks with cagrilintide 4.5 mg monotherapy versus −3.0 % with placebo, and −8.6 % with liraglutide 3.0 mg as active reference
CagriSema (cagrilintide with semaglutide) in obesity	Evidence extract	−22.7 % body weight at 68 weeks versus −2.3 % with placebo in adults with obesity without diabetes
CagriSema (cagrilintide with semaglutide) in type 2 diabetes	Evidence extract	−13.7 % body weight and −1.8 % HbA1c at 68 weeks in type 2 diabetes
Liraglutide in prediabetes	Evidence extract	Time to onset of type 2 diabetes over 160 weeks: hazard ratio 0.21
Liraglutide in adolescent obesity	Evidence extract	BMI z-score reduction of 0.22 versus 0.01 with placebo at 56 weeks
Liraglutide in sleep apnoea	Evidence extract	Apnoea–hypopnoea index reduced by 12.2 events/hour versus 6.1 with placebo at 32 weeks
Liraglutide in type 1 diabetes (adjunct)	Evidence extract	HbA1c reduction of approximately 0.2 % with increased hypoglycaemia and hyperketonaemia
Dulaglutide in obesity	Evidence extract	−4.6 kg at 4.5 mg over 52 weeks in type 2 diabetes
Exenatide in obesity	Evidence extract	−2.3 to −3.6 kg
Exenatide in gastric emptying	Evidence extract	Marked acute delay in gastric emptying that shows partial tachyphylaxis with continued twice-daily dosing
Lixisenatide in obesity	Evidence extract	−1.8 to −2.7 kg
Orforglipron in obesity	Evidence extract	−14.7 % body weight at 36 weeks with 45 mg in the phase 2 trial versus −2.3 % with placebo
Orforglipron in type 2 diabetes	Evidence extract	−2.1 % HbA1c at 26 weeks with 45 mg versus −0.4 % with placebo
Danuglipron in type 2 diabetes	Evidence extract	−1.16 % HbA1c at 16 weeks with 120 mg twice daily versus placebo
Survodutide in obesity	Evidence extract	−14.9 % body weight at 46 weeks with 6.0 mg in phase 2 versus −2.8 % with placebo
Mazdutide in obesity	Evidence extract	−14.4 % body weight at 48 weeks with 6 mg in a Chinese phase 3 trial versus −0.3 % with placebo
Mazdutide in type 2 diabetes	Evidence extract	−1.8 % HbA1c at 24 weeks with 6 mg
Pramlintide in type 1 diabetes (adjunct)	Evidence extract	HbA1c reduction of approximately 0.3 % with weight reduction of 1.4 kg and reduced insulin requirement
Pramlintide in type 2 diabetes	Evidence extract	HbA1c −0.62 % versus −0.18 % with placebo at 52 weeks, with weight −1.4 kg
Teduglutide in mucosal barrier	Evidence extract	Response defined as ≥20 % reduction in parenteral support volume in 63 % versus 30 % with placebo at 24 weeks
Tesamorelin in lipodystrophy	Evidence extract	Visceral adipose tissue reduced by 15.2 % versus 5.0 % increase with placebo at 26 weeks
Tesamorelin in gh axis	Evidence extract	IGF-1 rose by a mean of 81 ng/mL, with 34 % of participants exceeding the upper limit of normal at some point
Sermorelin in gh axis	Evidence extract	Peak stimulated growth hormone response used diagnostically; a peak below 5 µg/L after sermorelin supports pituitary rather than hypothalamic origin of deficiency
Ipamorelin in gastric emptying	Evidence extract	A phase 2 programme in post-operative ileus did not meet its primary endpoint and development was discontinued
GHRP-2 in gh axis	Evidence extract	A peak growth hormone below 16 ng/mL after 100 µg intravenously supports severe adult growth-hormone deficiency in the approved Japanese diagnostic criteria
AOD-9604 in obesity	Evidence extract	A 12-week phase 2b trial in 300 participants did not demonstrate a statistically significant difference in body weight versus placebo at any dose
Larazotide acetate in mucosal barrier	Evidence extract	A phase 2b trial met its primary endpoint on symptom scores at the 0.5 mg dose; the subsequent phase 3 trial was discontinued for futility at interim analysis
Thymosin alpha-1 in immune modulation	Evidence extract	Meta-analyses of hepatitis B trials report higher sustained virological response with thymosin alpha-1 as monotherapy or adjunct; a large Chinese randomised trial in sepsis reported a mortality…

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