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Safety evidence center

Explore adverse-event reports, controlled safety studies and evidence gaps. Case reports identify possible signals, not incidence or proven causation. No reported harm does not establish safety.

Body-system filters are text-based discovery aids, not clinical diagnoses. Regulatory warnings and prescribing guidance require separate, current source review.

37 matching summaries

Human-first editorial reading order—not an effectiveness or quality ranking. Design, topic and intervention-candidate labels assist discovery; they are not formal appraisals. Result-direction and sample-size filters only use existing verified metadata; missing values are excluded when those filters are active. Study counts are publications, not unique trials or participants.

Evidence & review standardsSafety center

37 results · Page 1 of 4

Human · Randomized trial · 2026-06-06

Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial.

Randomized, double-blind phase 3 trial compared weekly retatrutide with placebo for 40 weeks. The primary outcome was HbA1c, a blood-sugar marker; weight change was secondary.

Population, studied exposure & key finding
Population
537 adults with type 2 diabetes inadequately controlled by diet and exercise alone were randomized.
Studied dose & duration
Not extracted or not reported in the reviewed source.
Finding
HbA1c fell 1·69–1·94 percentage points across retatrutide groups versus 0·81 with placebo. Weight fell 11·5–15·3% versus 2·6%. Gastrointestinal events were generally mild or moderate; adverse-event discontinuations were 2–5% versus 0%. No severe low blood sugar occurred. Two deaths were judged unrelated to treatment.

Abstract summarized · Verified intervention · Summary quality not appraised

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Human · Randomized trial · 2025-03-29

Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes.

Randomized trial comparing oral semaglutide with placebo alongside standard care for cardiovascular death, nonfatal heart attack or stroke.

Population, studied exposure & key finding
Population
9650 adults aged 50 or older with type 2 diabetes and cardiovascular disease, chronic kidney disease or both; median follow-up was 49.5 months.
Studied dose & duration
Not extracted or not reported in the reviewed source.
Finding
The primary cardiovascular outcome occurred in 12.0% versus 13.8%. Confirmatory secondary outcomes, including kidney disease events, did not differ significantly. Serious adverse events occurred in 47.9% versus 50.3%, and digestive disorders in 5.0% versus 4.4%.

Abstract summarized · Intervention candidate · Summary quality not appraised

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Human · Randomized trial · 2023-06-23

Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial.

A 32-week, double-blind phase 2 trial randomized adults with type 2 diabetes to weekly CagriSema, semaglutide or cagrilintide. The primary outcome was change in HbA1c.

Population, studied exposure & key finding
Population
The trial included 92 adults with type 2 diabetes and BMI of at least 27 who used metformin, with or without an SGLT2 inhibitor: 31 received CagriSema, 31 semaglutide and 30 cagrilintide.
Studied dose & duration
Not extracted or not reported in the reviewed source.
Finding
HbA1c fell 2.2 percentage points with CagriSema, 1.8 with semaglutide and 0.9 with cagrilintide. CagriSema was superior to cagrilintide, but not semaglutide, for the primary outcome. Weight fell 15.6%, versus 5.1% and 8.1%; gastrointestinal events were usually mild or moderate.

Abstract summarized · Intervention candidate · Summary quality not appraised

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Human · Randomized trial · 2022-10-27

LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial.

A 12-week randomized, double-blind phase 1b trial in adults with type 2 diabetes compared ascending retatrutide doses with placebo and dulaglutide. Safety and tolerability were primary outcomes; glucose, weight and drug-processing measures were secondary.

Population, studied exposure & key finding
Population
72 participants received treatment across retatrutide groups, placebo (15 participants) and dulaglutide (five participants).
Studied dose & duration
Not extracted or not reported in the reviewed source.
Finding
Adverse events affected 63% with retatrutide, 60% with dulaglutide and 54% with placebo; gastrointestinal problems were most common. In the three highest retatrutide groups, HbA1c fell 1·2–1·6 percentage points more than placebo. The highest group lost 8·96 kg more than placebo.

Abstract summarized · Verified intervention · Summary quality not appraised

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Human · Randomized trial · 2021-10-18

Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial.

SURPASS-4 randomized adults with type 2 diabetes and high cardiovascular risk to once-weekly tirzepatide or titrated insulin glargine.

Population, studied exposure & key finding
Population
Participants had inadequately controlled type 2 diabetes despite oral glucose-lowering medications and established or high cardiovascular risk.
Studied dose & duration
Not extracted or not reported in the reviewed source.
Finding
At one year, tirzepatide lowered HbA1c more than glargine and caused less hypoglycemia; adjudicated cardiovascular events were not increased.

Abstract summarized · Intervention candidate · Summary quality not appraised

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Human · Randomized trial · 2021-06-27

Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial.

A double-blind randomized phase 3 trial compared once-weekly tirzepatide at three doses with placebo as monotherapy in adults with type 2 diabetes.

Population, studied exposure & key finding
Population
Adults with type 2 diabetes inadequately controlled by diet and exercise, who had not used injectable diabetes therapy, were studied.
Studied dose & duration
Not extracted or not reported in the reviewed source.
Finding
All tirzepatide doses improved HbA1c, fasting glucose, body weight, and target attainment versus placebo. Gastrointestinal events were the most frequent adverse events.

Abstract summarized · Intervention candidate · Summary quality not appraised

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Human · Randomized trial · 2019-06-11

Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.

Randomized safety trial comparing oral semaglutide with placebo for cardiovascular death, nonfatal heart attack or stroke.

Population, studied exposure & key finding
Population
3183 people with type 2 diabetes at high cardiovascular risk; median time in the trial was 15.9 months.
Studied dose & duration
Not extracted or not reported in the reviewed source.
Finding
Primary cardiovascular events occurred in 3.8% versus 4.8%, meeting the trial's safety criterion. Cardiovascular deaths were 0.9% versus 1.9%; nonfatal heart attacks were 2.3% versus 1.9%, and nonfatal strokes 0.8% versus 1.0%. Digestive adverse events led to more treatment discontinuations with oral semaglutide.

Abstract summarized · Intervention candidate · Summary quality not appraised

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Human · Randomized trial · 2018-10-04

Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial.

Double-blind phase 2 trial comparing weekly LY3298176, now known as tirzepatide, at four doses with dulaglutide or placebo.

Population, studied exposure & key finding
Population
The study randomized 318 adults with inadequately controlled type 2 diabetes; 316 received treatment, and 258 completed 26 weeks of treatment.
Studied dose & duration
Not extracted or not reported in the reviewed source.
Finding
HbA1c reductions were dose-dependent, reaching -1·94% with 15 mg versus -0·06% with placebo and -1·21% with dulaglutide. Weight change ranged from -0·9 kg to -11·3 kg. Gastrointestinal events increased with dose; no severe hypoglycaemia was reported.

Abstract summarized · Intervention candidate · Summary quality not appraised

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Human · Animal · Cell / tissue · Randomized trial · 2018-10-03

LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept.

A full-text phase 1 program tested the dual GIP/GLP-1 agonist LY3298176 in cells and mice, then in randomized, double-blind human studies against placebo; dulaglutide was an active control in healthy participants. Safety and tolerability were primary.

Population, studied exposure & key finding
Population
A total of 142 people received LY3298176, placebo or dulaglutide: 56 in the single-dose study, 33 healthy participants in the four-week multiple-dose study and 53 people with type 2 diabetes in the proof-of-concept study.
Studied dose & duration
Not extracted or not reported in the reviewed source.
Finding
After four weeks, higher-dose groups with diabetes had lower fasting glucose versus placebo, and several healthy-participant groups lost more weight versus placebo. Gastrointestinal events were dose-dependent and mild to moderate; vomiting limited the single 8 mg dose.

Full paper summarized · Intervention candidate · Summary quality not appraised

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Human · Randomized trial · 2018-08-16

Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial.

A 52-week, randomized, double-blind phase 2 trial compared five once-daily semaglutide doses with liraglutide and matched placebo, alongside diet and physical-activity counseling. Percentage weight loss at week 52 was the primary outcome.

Population, studied exposure & key finding
Population
The trial randomized 957 adults without diabetes who had BMI of at least 30 across 71 sites in eight countries.
Studied dose & duration
Not extracted or not reported in the reviewed source.
Finding
Estimated weight loss was 2.3% with placebo, 6.0% to 13.8% across semaglutide groups and 7.8% with liraglutide. Every semaglutide dose outperformed placebo; doses of 0.2 mg or more outperformed liraglutide. Dose-related gastrointestinal symptoms, mainly nausea, were most common.

Abstract summarized · Intervention candidate · Summary quality not appraised

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Human · Randomized trial · 2017-02-23

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial.

A randomized, double-blind human trial compared liraglutide with placebo. The primary outcome was time to type 2 diabetes by 160 weeks.

Population, studied exposure & key finding
Population
2254 adults with prediabetes and obesity, or overweight with additional conditions, were randomized.
Studied dose & duration
Participants received subcutaneous liraglutide 3.0 mg or matched placebo daily, alongside reduced-calorie eating and increased activity.
Finding
Diabetes was diagnosed during treatment in 2% versus 6%. Weight fell 6.1 versus 1.9 percent at 160 weeks. Serious adverse events occurred in 15% versus 13%.

Abstract summarized · Intervention candidate · Summary quality not appraised

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Human · Randomized trial · 2016-09-15

Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.

Randomized cardiovascular-safety trial comparing semaglutide with placebo, tracking cardiovascular death, nonfatal heart attack or stroke.

Population, studied exposure & key finding
Population
3297 people with type 2 diabetes, treated for 104 weeks. Most had cardiovascular disease, chronic kidney disease or both.
Studied dose & duration
Not extracted or not reported in the reviewed source.
Finding
The primary outcome occurred in 6.6% versus 8.9%, meeting the trial's cardiovascular-safety criterion. Cardiovascular death rates were similar. Nonfatal strokes were fewer, but heart attacks showed no statistically clear difference. Kidney complications were fewer, while diabetic-eye complications were more frequent. Serious adverse events were fewer overall, but more participants stopped treatment, mainly for digestive symptoms.

Abstract summarized · Intervention candidate · Summary quality not appraised

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