Cardiometabolic Profiles of Oral and Subcutaneous Glucagon-Like Peptide-1 Receptor Mono-Agonists in Adults With Overweight or Obesity: A Systematic Review and Network Meta-Analysis.
Semaglutide isn’t just making waves—it’s running the show in cardiometabolic research. A new meta-analysis pooled data from 19 randomized controlled trials, covering over 13,000 adults with overweight or obesity. The target: glucagon-like peptide-1 (GLP-1) receptor mono-agonists, including semaglutide, liraglutide, and the oral newcomer orforglipron. The researchers wanted to see which peptide scored best across a full spectrum of cardiometabolic markers.
Diabetes Obes Metab
by Lu Y, Chen J, Guo Y et al.
“Cardiometabolic Profiles of Oral and Subcutaneous Glucagon-Like Peptide-1 Receptor Mono-Agonists in Adults With Overweight or Obesity: A Systematic Review and Network Meta-Analysis. Lu Y(1), Chen J(1), Guo Y(1), Ding H(1), Liu YL(2), Van Name MA(3), Sharifi M(4), Lu Y(5)(6), Chen Y(7). Author information: (1)Ividence Inc, Newark, Delaware, USA. (2)UT Southwestern Medical Center, Peter O'Donnell Jr. School of Public Health, Dallas, Texas, USA. (3)Pediatric Endocrinology, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut, USA. (4)Section of General Pediatrics, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut, USA. (5)Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. (6)Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut, USA. (7)The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AIMS: To characterize the cardiometabolic profiles of oral and subcutaneous glucagon-like peptide-1 (GLP-1) receptor mono-agonists in adults with overweight or obesity, with or without type 2 diabetes (T2D), using network meta-analysis (NMA). MATERIALS AND METHODS: PubMed, Embase and CENTRAL were searched (January 2014-November 2025) for randomized controlled trials (RCTs) evaluating GLP-1 receptor mono-agonists (semaglutide, liraglutide and orforglipron) in adults with overweight or obesity. The primary outcome was the cardiometabolic efficacy index (CEI), a ranking-based composite (0 to 1) summarizing performance across seven cardiometabolic endpoints: total body weight loss percentage, triglycerides, HDL cholesterol-C, LDL-C, waist circumference, HbA1c and systolic blood pressure. Secondary outcomes included treatment effects for each individual CEI component. RESULTS: Nineteen RCTs (N = 13 117) were analysed. Semaglutide 7.2 mg achieved the highest CEI (0.86), followed by orforglipron 36 mg (bioequivalent to Foundayo 17.2 mg tablet) (0.68) and semaglutide 2.4 mg (0.66), all exhibiting placebo-adjusted weight reductions ≥ 10%. CEI rankings were generally consistent across T2D and non-T2D subgroups. Among oral formulations in non-T2D adults, OFG 36 mg showed a CEI comparable to oral semaglutide 25 mg (0.67 vs 0.63). CONCLUSIONS: Higher-dose GLP-1 receptor mono-agonists, particularly semaglutide 7.2 mg and orforglipron 36 mg (Foundayo 17.2 mg tablet), demonstrated the most consistent multidimensional cardiometabolic improvements, although domain-specific differences were observed across agents. © 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.”
Here’s what they did differently: Instead of zeroing in on just weight loss or blood sugar, they built a composite “cardiometabolic efficacy index” (CEI) that crunched seven endpoints into a single number. The results weren’t subtle.
Key takeaway: Semaglutide at 7.2 mg led the pack, hitting a CEI of 0.86. Orforglipron (36 mg, oral) followed at 0.68, with semaglutide 2.4 mg earning a solid 0.66. All three outperformed placebo by delivering at least 10% weight reduction. This was true for both people with and without type 2 diabetes.
Breakdown of what the CEI measured:
Total body weight loss (percentage)
Triglycerides
HDL cholesterol
LDL cholesterol
Waist circumference
HbA1c (marker of glucose control)
Systolic blood pressure
Oral options are catching up. Among non-diabetic adults, orforglipron’s CEI nearly matched oral semaglutide 25 mg (0.67 vs 0.63). This is big for anyone exploring alternatives to subcutaneous injection.
Researchers comparing delivery routes, or wondering how these research peptides stack up across body composition, lipids, and glucose, finally have a head-to-head scoreboard. If you’re sourcing compounds or setting up new protocols, the high marks for semaglutide are worth a look. For more specifics on sourcing, check our vendor directory or visit the semaglutide research page.
Bottom line: Higher-dose GLP-1 mono-agonists, especially semaglutide, keep turning in strong, multidimensional results. That’s good news for anyone following this research field.
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