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Semaglutide

GLP-1 receptor agonists — Living Evidence Monitor

Data last updated 16 studies cited

How this page is produced

Generated by the ModernDoc Research Monitor from peer-reviewed literature. Every statistic is automatically checked against its cited source and screened for retractions before it is published. This is an AI-assisted evidence summary, not a clinician endorsement and not medical advice. Read how we build and check these pages.

KEY FINDINGS

One-year weight loss with oral semaglutide versus lifestyle modification alone
-10.9%
95% CI: -12.7% to -9.1%
Source [1] · DOI ·
One-year weight loss with subcutaneous semaglutide versus lifestyle modification alone
-9.8%
95% CI: -10.6% to -9.1%
Source [1] · DOI ·
All-cause mortality reduction with subcutaneous semaglutide (only drug with this benefit)
RR 0.81
95% CI: 0.72 to 0.93
Source [1] · DOI ·
Myocardial infarction reduction with subcutaneous semaglutide
RR 0.72
95% CI: 0.61 to 0.85
Source [1] · DOI ·
Heart failure risk reduction with subcutaneous semaglutide
RR 0.43
95% CI: 0.21 to 0.84
Source [1] · DOI ·
Discontinuation due to adverse events with oral semaglutide (range across drugs)
RR 1.9 to 4.2
Source [1] · DOI ·
Gastrointestinal events with oral semaglutide (range across drugs)
RR 3.1 to 4.2
Source [1] · DOI ·
Femoral fracture risk with semaglutide versus DPP-4 inhibitors in older adults with T2DM and overweight/obesity
HR 0.488
95% CI: 0.367-0.649
Source [2] · DOI ·
Fall risk with semaglutide versus DPP-4 inhibitors in older adults with T2DM and overweight/obesity
HR 0.663
95% CI: 0.612-0.718
Source [2] · DOI ·
Absolute femoral fracture rates with semaglutide versus DPP-4 inhibitors
0.3% vs. 0.5%
Source [2] · DOI ·
Absolute fall rates with semaglutide versus DPP-4 inhibitors
3.6% vs. 5.4%
Source [2] · DOI ·
All-cause mortality with incretin-based therapy vs SGLT2i in AF/HFpEF patients
HR 0.721
95% CI: 0.634-0.820
Source [3] · DOI ·
Myocardial infarction with incretin-based therapy vs SGLT2i in AF/HFpEF patients
HR 0.583
Source [3] · DOI ·
Major adverse cardiovascular events with incretin-based therapy vs SGLT2i in AF/HFpEF patients
HR 0.709
Source [3] · DOI ·
Absolute all-cause mortality rates at 1 year (incretin vs SGLT2i)
5.3% vs. 7.3%
Source [3] · DOI ·
Proportion achieving improvement in liver fibrosis without MASH worsening with semaglutide 2.4mg versus placebo at week 52 in MASH patients with F2-F4c fibrosis
30% vs 16%
95% CI: 1.88 to 26.23 (EDP)
Source [4] · DOI ·
Proportion achieving improvement in liver fibrosis without MASH worsening with zalfermin 30mg plus semaglutide 2.4mg versus placebo (non-significant)
24% vs 16%
95% CI: -3.82 to 19.79 (EDP)
Source [4] · DOI ·
Incident diabetes risk with semaglutide versus liraglutide (overall)
HR 0.88
95% CI: 0.78, 0.99
Source [5] · DOI ·
Incident diabetes risk with semaglutide versus liraglutide (first 6 months)
HR 0.99
95% CI: 0.82-1.18
Source [5] · DOI ·
Cardiovascular disease risk with semaglutide versus liraglutide
HR 1.25
95% CI: 0.74-2.11
Source [5] · DOI ·
Myocardial infarction reduction with semaglutide (updated estimate from meta-analysis)
RR 0.70
95% CI: 0.62-0.80
Source [6] · DOI ·
Broad CAD-related composite outcome with semaglutide
RR 0.80
95% CI: 0.73-0.87
Source [6] · DOI ·
Acute coronary syndrome reduction with semaglutide
RR 0.77
95% CI: 0.70-0.85
Source [6] · DOI ·
Unstable angina reduction with semaglutide
RR 0.82
95% CI: 0.70-0.96
Source [6] · DOI ·
Angina pectoris reduction with semaglutide
RR 0.73
95% CI: 0.60-0.89
Source [6] · DOI ·
Oral semaglutide reduced risk of major adverse cardiovascular events in SOUL trial
14% MACE reduction
Source [7] · DOI ·
MACE benefits varied significantly by baseline HbA1c, greater at higher baseline HbA1c
P-interaction = .04
Source [7] · DOI ·
Greater HbA1c reductions at 13 and 52 weeks associated with larger MACE risk decreases
P-interactions .005 and < .001
Source [7] · DOI ·
MACE benefits were consistent across BMI changes at weeks 13 and 52
P-interactions .88 and .64
Source [7] · DOI ·
One-year heart-failure risk with tirzepatide versus semaglutide among patients with type 2 diabetes
RR 0.82
95% CI: 0.78-0.86
Source [8] · DOI ·
Reported one-year heart-failure risk difference between tirzepatide and semaglutide among patients with type 2 diabetes, favoring tirzepatide
1.5%
Source [8] · DOI ·
One-year heart-failure risk with tirzepatide versus semaglutide among patients without diabetes
RR 0.60
95% CI: 0.55-0.65
Source [8] · DOI ·
Reported one-year heart-failure risk difference between tirzepatide and semaglutide among patients without diabetes, favoring tirzepatide
0.9%
Source [8] · DOI ·
Effect modification by diabetes status for atrial fibrillation at 1 year
P = 0.003
Source [8] · DOI ·
Effect modification by diabetes status for heart failure at 1 year
P < 0.001
Source [8] · DOI ·
Effect modification by diabetes status for acute myocardial infarction at 1 year
P = 0.019
Source [8] · DOI ·
HbA1c reduction with once-weekly semaglutide 1.0 mg versus insulin glargine or other GLP-1 receptor agonists in insulin-naive adults with T2DM uncontrolled on oral drugs; low-certainty evidence
MD -0.64%
95% CI: -0.80 to -0.47
Source [9] · DOI ·
Body-weight change with semaglutide versus other GLP-1 receptor agonists; I²=0% and moderate-certainty evidence
MD -3.72 kg
95% CI: -4.17 to -3.28
Source [9] · DOI ·
Hypoglycemia risk with semaglutide versus insulin glargine; moderate-certainty evidence
RR 0.53
Source [9] · DOI ·
Pooled change in AST with subcutaneous semaglutide versus placebo among adults with NAFLD or NASH
MD -6.72 U/L
95% CI: -11.79 to -1.64
Source [10] · DOI ·
NASH resolution without fibrosis progression with subcutaneous semaglutide versus placebo
RR 2.14
95% CI: 1.44-3.17
Source [10] · DOI ·
Fibrosis-stage improvement with subcutaneous semaglutide versus placebo; the pooled result was not statistically significant
RR 1.14
95% CI: 0.63-2.05
Source [10] · DOI ·
Pooled weight change with subcutaneous semaglutide versus placebo among adults with NAFLD or NASH; P = .05
MD -6.99%
95% CI: -13.92 to -0.06
Source [10] · DOI ·
Pooled HbA1c change with subcutaneous semaglutide versus placebo among adults with NAFLD or NASH
MD -1.29%
95% CI: -1.46 to -1.13
Source [10] · DOI ·
Severe hypoglycaemia occurred at a lower rate with semaglutide 2.0 mg plus dose-reduced insulin glargine versus dose-titrated insulin glargine at 40 weeks (p=0.02).
Rate ratio 0.45
95% CI: 0.23-0.87
Source [11] · DOI ·
Gastrointestinal adverse-event counts were higher with semaglutide 2.0 mg plus dose-reduced insulin glargine than with dose-titrated insulin glargine; these are event counts rather than participant-level incidence rates, and the abstract reported no new safety concerns.
310 vs. 32 events
Source [11] · DOI ·
HbA1c reduction with semaglutide 2.0 mg plus dose-reduced insulin glargine versus dose-titrated insulin glargine at 40 weeks
ETD -0.74%
95% CI: -0.90% to -0.59%
Source [11] · DOI ·
Body-weight change with semaglutide 2.0 mg plus dose-reduced insulin glargine versus dose-titrated insulin glargine at 40 weeks
ETD -8.5 kg
95% CI: -9.5 to -7.4 kg
Source [11] · DOI ·
Relative daily insulin-dose change with semaglutide 2.0 mg plus dose-reduced insulin glargine versus dose-titrated insulin glargine at 40 weeks
ETD -121.9%
95% CI: -143.1% to -100.6%
Source [11] · DOI ·
Diabetes Treatment Satisfaction Questionnaire change score with semaglutide 2.0 mg plus dose-reduced insulin glargine versus dose-titrated insulin glargine at 40 weeks
ETD 2.6
95% CI: 1.6 to 3.5
Source [11] · DOI ·
Adjusted relative likelihood of achieving ≥15% weight loss with semaglutide versus liraglutide among adults with obesity in a retrospective real-world cohort.
aHR 1.77
95% CI: 1.56-2.01
Source [12] · DOI ·
Mean weight change at 12 months among semaglutide initiators with obesity in a retrospective real-world cohort.
-5.9%
Source [12] · DOI ·
Key preregistered secondary outcome of heavy drinking days during the last 4 treatment weeks with oral semaglutide versus placebo in treatment-seeking adults with moderate-to-severe alcohol use disorder; laboratory-assessed craving and drinks per day were not significantly reduced.
b=-0.580
95% CI: -1.012 to -0.148
Source [13] · DOI ·
Exploratory effect on drinks per drinking day with oral semaglutide versus placebo in adults with alcohol use disorder.
b=-1.177
95% CI: -2.307 to -0.047
Source [13] · DOI ·
Exploratory difference in the rate of reduction in alcohol-related negative consequences with oral semaglutide versus placebo.
b=-4.618
95% CI: -8.651 to -0.585
Source [13] · DOI ·
Exploratory comparison of the proportion reducing World Health Organization risk drinking level by at least one category with oral semaglutide versus placebo; the abstract did not report group percentages.
Wald χ2=4.01
Source [13] · DOI ·
Exploratory effect on cannabis-use days with oral semaglutide versus placebo among adults enrolled for alcohol use disorder.
b=-1.434
95% CI: -2.568 to -0.301
Source [13] · DOI ·
Pooled mean percentage body-weight regain from end of treatment to follow-up after stopping semaglutide 2.4 mg, based on six studies
7.19%
95% CI: 6.42-7.96
Source [14] · DOI ·
Percentage change in body weight with subcutaneous semaglutide versus placebo in adults with overweight or obesity without type 2 diabetes
MD -11.85%
95% CI: -12.81% to -10.90%
Source [15] · DOI ·
Treatment discontinuation due to adverse events with subcutaneous semaglutide versus placebo in adults with overweight or obesity without type 2 diabetes
RR 2.62
95% CI: 1.70-4.03
Source [15] · DOI ·
Model-estimated reduction at six months in %IOTF30, defined as BMI expressed as a percentage of the age- and sex-specific IOTF obesity threshold.
5.17 pp reduction at 6 months
95% CI: 3.98 to 6.36
Source [16] · DOI ·
Model-estimated reduction at 12 months in %IOTF30, defined as BMI expressed as a percentage of the age- and sex-specific IOTF obesity threshold.
10.33 pp reduction at 12 months
95% CI: 7.96 to 12.71
Source [16] · DOI ·
Proportion of participants who achieved a reduction in %IOTF30 exceeding 10 percentage points.
63%
Source [16] · DOI ·
No statistically significant modification of treatment response by neurodevelopmental-disorder status was detected among 56 Pediatric Obesity Center participants; the analysis was underpowered and should not be interpreted as evidence of equivalent response.
interaction p=0.83
Source [16] · DOI ·

SOURCES

  1. [1]Nong, Kailei et al.. Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis.. BMJ (Clinical research ed.). 2026. DOI (opens in new tab)
  2. [2]Chen, Hsin-Yu et al.. Lower fall and femoral fracture risks with semaglutide and tirzepatide compared with DPP-4 inhibitors in older adults with type 2 diabetes.. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2026. DOI (opens in new tab)
  3. [3]Ahmed, Faizan et al.. GLP-1 Receptor Agonists or Dual GLP-1/GIP Receptor Agonists vs. SGLT2 Inhibitors in Patients with Atrial Fibrillation and HFpEF: A Propensity-Matched Real-World Analysis.. Journal of clinical medicine. 2026. DOI (opens in new tab)
  4. [4]Loomba, Rohit et al.. Efficacy and safety of zalfermin co-administered with semaglutide in participants with fibrosis and cirrhosis due to metabolic dysfunction-associated steatohepatitis: a phase 2, dose-ranging, double-blind, randomised controlled trial.. The lancet. Gastroenterology & hepatology. 2026. DOI (opens in new tab)
  5. [5]Cannon, Ethan J et al.. Semaglutide vs. liraglutide and incidence of diabetes and cardiovascular disease: A target trial emulation using real-world data.. British journal of clinical pharmacology. 2026. DOI (opens in new tab)
View all 16 cited studiesShow fewer sources
  1. [6]Zhou, Xiao-Yu et al.. Coronary artery disease -related outcomes associated with semaglutide and tirzepatide in type 2 diabetes mellitus and obesity: a systematic review and meta-analysis.. Nutrition, metabolism, and cardiovascular diseases : NMCD. 2026. DOI (opens in new tab)
  2. [7]Inzucchi, Silvio E et al.. Oral Semaglutide and CV Benefits in the SOUL Trial: How Do Baseline or Changes in HbA1c or BMI Affect Clinical Outcomes?. The Journal of clinical endocrinology and metabolism. 2026. DOI (opens in new tab)
  3. [8]Azzam, Ahmed Y et al.. Cardiovascular and Cerebrovascular Outcomes Risk Reduction Associated With Semaglutide vs Tirzepatide: A Target Trial Emulation.. JACC. Advances. 2026. DOI (opens in new tab)
  4. [9]Aljulajil, Faisal A et al.. Efficacy and Safety of Once-Weekly Semaglutide Versus Basal Insulin and Other GLP-1 Receptor Agonists in Adults With Type 2 Diabetes Uncontrolled on Oral Antidiabetic Drugs: A Systematic Review and Pairwise Meta-Analysis.. Cureus. 2026. DOI (opens in new tab)
  5. [10]Khan, Suleman et al.. Therapeutic role of semaglutide in metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis: A systematic review and meta-analysis of placebo-controlled trials with GRADE evidence assessment.. Medicine. 2026. DOI (opens in new tab)
  6. [11]Rodbard, Helena W et al.. Efficacy and Safety of Once-Weekly Semaglutide 2.0 mg as an Add-On to Dose-Reduced Insulin Glargine versus Dose-Titrated Insulin Glargine in People With Type 2 Diabetes and Overweight (SUSTAIN OPTIMIZE).. Diabetes, obesity & metabolism. 2026. DOI (opens in new tab)
  7. [12]Hwang, Inyoung et al.. Real-World Comparative Weight Loss of GLP-1 Receptor Agonists in the All of Us Research Program: A Retrospective Cohort Study.. Drug design, development and therapy. 2026. DOI (opens in new tab)
  8. [13]Schacht, Joseph P et al.. Oral Semaglutide for Alcohol Use Disorder: A Randomized Clinical Trial.. The American journal of psychiatry. 2026. DOI (opens in new tab)
  9. [14]Patel, Henna et al.. Post-cessation Weight Regain After Weight Management Medications: A Systematic Review and Meta-Analysis.. Cureus. 2026. DOI (opens in new tab)
  10. [15]Naz, Faryal et al.. Effectiveness & safety of semaglutide in weight reduction in obese nondiabetic patients: A systematic review and meta-analysis.. Medicine. 2026. DOI (opens in new tab)
  11. [16]Thorsteinsdottir, Sigrun et al.. Real-World Use of Subsidised Semaglutide in Icelandic Children With Obesity: A Nationwide Retrospective Cohort Study.. Pediatric obesity. 2026. DOI (opens in new tab)

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