Effect of oral semaglutide on cardiometabolic risk factors in overweight and obese individuals with or without diabetes: a systematic review and meta-analysis

Oral semaglutide, compared with placebo, was associated with significant reductions in body weight, BMI, waist circumference, HbA1c, fasting glucose, and blood pressure in overweight and obese adults with or without diabetes. Gastrointestinal symptoms were the most common adverse events, and cardiovascular events appeared less frequent with semaglutide. These findings come from a systematic review and meta-analysis of 13 randomized controlled trials involving 26,284 participants.

Meta-analysis — Systematic review and meta-analysis of RCTs. Population: Overweight and obese adults with or without diabetes, from randomized controlled trials. Sample size: 26,284 participants from 13 RCTs. Follow-up: 6 months (main pooled estimates). Interventions: oral semaglutide.

Across 13 RCTs involving 26,284 participants, oral semaglutide significantly reduced body weight, BMI, waist circumference, HbA1c, fasting plasma glucose, systolic blood pressure, and diastolic blood pressure compared with placebo over 6 months. These benefits were consistent across different follow-up durations and doses. Gastrointestinal symptoms were the most common adverse events (OR 2.69; nausea OR 3.13; vomiting OR 6.25; all p < 0.001). Semaglutide also showed a protective effect on cardiovascular events (OR 0.64; p = 0.006).

Researchers studying semaglutide will be interested in this large pooled dataset because it consolidates evidence from 13 placebo-controlled RCTs on oral semaglutide's effects on weight, glycaemic control, blood pressure, and cardiovascular events. It does not establish mechanisms, optimal dosing, durability beyond the pooled follow-up, or comparative performance against active controls.

Key findings

Oral semaglutide reduced body weight by an estimated 2.85 kg more than placebo (95% CI -4.03 to -1.66; p < 0.001).
It reduced BMI by 0.66 kg/m² (95% CI -0.95 to -0.36; p < 0.001) and waist circumference by 1.79 cm (95% CI -2.63 to -0.95; p < 0.001).
It reduced HbA1c by 0.94% (95% CI -1.13 to -0.76; p < 0.001) and fasting plasma glucose by 26.91 mg/dL (95% CI -33.56 to -20.26; p < 0.001).
Systolic blood pressure fell by 2.71 mmHg (95% CI -3.70 to -1.72; p < 0.001) and diastolic blood pressure by 0.77 mmHg (95% CI -1.38 to -0.17; p = 0.01).
Gastrointestinal adverse events were more common with semaglutide (OR 2.69; nausea OR 3.13; vomiting OR 6.25; all p < 0.001).
Semaglutide was associated with fewer cardiovascular events than placebo (OR 0.64; p = 0.006).

Limitations

Main pooled estimates were reported at 6 months; longer-term outcomes are not established.
Only placebo-controlled trials were included, so no comparison with other active treatments is possible.
Doses and follow-up durations varied across included trials, which may introduce heterogeneity.
Meta-analysis results depend on the quality and reporting of the included RCTs.

The record

Journal: BMC pharmacology & toxicology 27(1): 98
Published: 2026-05-21
PMID: 42163419 — DOI: 10.1186/s40360-026-01149-5
MeSH terms: Humans, Diabetes Mellitus, Obesity, Hypoglycemic Agents, Administration, Oral, Overweight, Glucagon-Like Peptides, Randomized Controlled Trials as Topic, Cardiometabolic Risk Factors, Semaglutide
Author countries: Denmark, Iran, UK, USA

Peptide profiles: Semaglutide.

All indexed evidence: Semaglutide trials & papers.