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Efp4.3
Efpeglenatide Research
Too few graded studies
21 peer-reviewed studies
What the evidence says
Too few graded studies
Efpeglenatide doesn't have enough studies with structured effect-size data yet to pool a verdict. Browse the studies below for individual findings.
Most evidence is from high-quality meta-analyses and randomised trials published 2019–2026 with a typical study size of 3,983 participants.
Based on 21 studies · 8 meta-analyses · 11 RCTs · 31,255 total participants
Confidence
High confidence
By outcome
Glycemic controlDose-dependent HbA1c reductions across the program; pooled meta-analysis HbA1c -0.84% vs placebo · Weeks to months
Too few graded studies20 studies
Cardiovascular & renal outcomesAMPLITUDE-O reduced the primary MACE composite by 27% vs placebo (HR 0.73) in high-risk type 2 diabetes · Over ~1.8 years
Too few graded studies9 studies
Weight & body compositionIn obesity without diabetes, placebo-adjusted weight loss of ~6.3-7.2 kg over 20 weeks (phase-2) · Months (titrated)
Too few graded studies8 studies
Safety profile
Too few graded studies5 studies
Active research area
17 studies in the last 5 years · Latest meta-analysis: 2025
In plain English: GLP-1 RAs reduce mortality and MACE in high-risk populations, highlighting benefits beyond glycemic control.
Galli M, Benenati S, Laudani C, Simeone B, Sarto G, Ortega-Paz L, Rocco E, Bernardi M, Spadafora L, D'Amario D, Greco E, Frati G, Federici M, Mehran R, Crea F, Angiolillo DJ, Sciarretta S. · Journal of the American College of Cardiology (2025)
We found conclusive, high-certainty evidence that GLP-1 RAs reduced all-cause death (incidence rate ratio [IRR]: 0.88; 95% CI: 0.84-0.92; needed to treat [NNT] = 121), CV death (IRR: 0.87; 95% CI: 0.81-0.92; NNT = 170), and MACE (IRR: 0.87; 95% CI: 0.83-0.91; NNT = 66), compared with controls.
GLP-1 RAs reduced serious adverse events (-9%), myocardial infarction (-15%), acute kidney failure (-9%), heart failure (-15%), and infections (-10%), but increased gastrointestinal (+63%) and gallbladder (+26%) disorders.
Analysis by GLP-1 RA type revealed potential differences in efficacy and safety profiles.
In plain English: These findings indicate that efpeglenatide may possess a broad, systemic preventive effect against metastatic cancers, potentially operating through mechanisms that are not restricted to individual organ systems.
Hsu CW, Zeng BS, Liang CS, Zeng BY, Hung CM, Stubbs B, Chen YW, Lei WT, Chen JJ, Chen PH, Su KP, Chen TY, Tseng PT. · International journal of molecular sciences (2025)
This NMA of 207,606 participants from 67 RCTs revealed that only efpeglenatide demonstrated a statistically significant reduction in metastatic cancer events compared to controls (odds ratio = 0.26, 95% confidence intervals = 0.09 to 0.70, p = 0.010, number needed to treat = 188.4).
Efpeglenatide's efficacy was not confined to specific cancer types.
Safety profiles were comparable across all treatments.
In plain English: Promising data also suggest benefits in common comorbidities, including obstructive sleep apnea, polycystic ovary syndrome, chronic kidney disease, and heart failure with preserved ejection fraction.GLP-1RAs represent a valuable pharmacotherapeutic option for gastroenterologists managing individuals with MASLD/MASH and cardiometabolic comorbid conditions.
Alkhouri N, Charlton M, Gray M, Noureddin M. · Expert opinion on investigational drugs (2025)
Expert opinion In Phase I - III trials, GLP-1RAs are associated with clinically relevant hepatic improvements including MASH resolution, liver fat reduction, and preventing worsening fibrosis.
Effects on cardiometabolic parameters align with type 2 diabetes/obesity Phase III data, comprising substantial improvements in glycemic, weight, and cardiovascular outcomes.
In plain English: This study compared the cardiovascular benefits of different GLP-1RAs, including reductions in cardiovascular events and improvements in multiple cardiovascular risk factors.
An X, Sun W, Wen Z, Duan L, Zhang Y, Kang X, Ji H, Sun Y, Jiang L, Zhao X, Gao Q, Lian F. · Diabetes, obesity & metabolism (2025)
GLP-1RAs did not significantly increase the incidence of adverse events, but Orforglipron and Taspoglutide significantly increased the incidence of gastrointestinal adverse events compared with placebo.
Conclusion This study compared the cardiovascular benefits of different GLP-1RAs, including reductions in cardiovascular events and improvements in multiple cardiovascular risk factors.
However, due to limitations in the quantity and quality of the included studies, the conclusions should be interpreted with caution.
In plain English: In this post hoc analysis from the AMPLITUDE-O trial, changes in LDL cholesterol together with UACR but not weight were estimated to statistically account for a modest portion of the reduction in risk of MACE with efpeglenatide.
Aims In the AMPLITUDE O trial, efpeglenatide reduced major cardiovascular events by 27% in 4076 individuals with Type 2 diabetes and established cardiovascular or kidney disease compared to placebo during a median follow-up of 1.81 years.
The hazard (95% CI) per 1-unit increase in each time-updated mediator (change from baseline or updated mean) was estimated using Cox models adjusted for the same variables as in the main AMPLITUDE-O results.
Of these, univariable analyses showed that only changes in HbA1c, LDL cholesterol, UACR and amylase accounted for 14%, 11%, 16% and 10%, respectively, of the effect of efpeglenatide on MACE.
In plain English: In high-risk people with type 2 diabetes, the degree of liver fibrosis, as estimated by FIB-4 score, was not related to incident cardiovascular outcomes.
Del Prato S, Li Z, Ramasundarahettige C, Branch KRH, Lam CSP, Lopes RD, Pratley R, Rosenstock J, Sattar N, Gerstein HC. · Cardiovascular diabetology (2024)
Results Baseline FIB-4 score was available for 4059 participants (99.6%) allowing subdivision of the population in tertiles.
During a median follow-up of 1.8 years, numerical increases in the incidence of all 3 outcomes did not change significantly across tertiles of FIB-4 score (P for trend ≥ 0.25) with negligible relationship of the score to incident outcomes (MACE HR, per 1 SD higher score, 95% CI: 1.00, 0.89-1.13).
Efpeglenatide's effect on all MACE outcomes did not vary across FIB-4 tertiles (all interaction p values ≥ 0.64).
In plain English: All efpeglenatide doses ≥1 mg significantly reduced HbA1c versus placebo (placebo-adjusted least squares [LS] mean changes 0.6-1.2%, P < 0.05 for all)... masked efpeglenatide 4 mg was noninferior to open-label liraglutide.
Rosenstock J, Sorli CH, Trautmann ME, Morales C, Wendisch U, Dailey G, Hompesch M, Choi IY, Kang J, Stewart J, Yoon KH. · Diabetes Care (2019)
Phase-2 'EXCEED 203' 12-week randomized, double-blind, placebo-controlled dose-ranging study in early type 2 diabetes (drug-naive or on metformin), referenced to open-label liraglutide 1.8 mg (exploratory)
All efpeglenatide doses of 1 mg or more lowered HbA1c by a placebo-adjusted 0.6-1.2% to a final HbA1c of 6.3-6.8%. In the exploratory comparison, masked efpeglenatide 4 mg was noninferior to open-label liraglutide
Greater weight loss with 3 and 4 mg vs placebo (placebo-adjusted -1.4 and -2.0 kg); no neutralizing antibodies detected
18Meta-AnalysisCited 77×n=27,018 · very large study2021
In plain English: Direct meta-analysis showed significant WLOP with... -3.20kg (-6.53 to 0.15) with efpeglenatide... -9.88kg (-13.17 to -6.59) with semaglutide SQ 2.4mg... Highest WLOP were with semaglutide SQ 2.4mg and <2.4mg, and liraglutide >1.8mg.
Vosoughi K, Atieh J, Khanna L, Khoshbin K, Prokop LJ, Davitkov P, Murad MH, Camilleri M. · EClinicalMedicine (2021)
Systematic review and frequentist network meta-analysis of 64 RCTs (n=27,018) comparing 7 GLP-1 agents on weight loss and adverse events in obesity
Efpeglenatide's weight loss over placebo was -3.20 kg, but its 95% CI (-6.53 to 0.15) crosses zero, so on these data it was not clearly better than placebo
Semaglutide 2.4 mg gave the largest weight loss (~-9.9 kg over placebo); discontinuation due to AEs was highest with taspoglutide and high-dose liraglutide
In plain English: The change in SBP varies only slightly by the drug-dose combination and appears to be related to the amount of weight loss.
Ali A, Siddiqui AA, Usman MS, Shahid I, Khan MS, Perswani P. · Clinical obesity (2025)
Subgroup analysis showed a significantly greater difference in SBP reduction for patients without diabetes (-3.80 [-4.24; -3.37]) when compared with patients with diabetes (-2.13 [-3.27; -1.00]).
Among patients with diabetes, liraglutide < 2 mg OD showed the greatest reduction in SBP (-3.78 [-6.27; -1.28]), while efpeglenatide ≤ 6 mg QW showed the greatest reduction in SBP (-6.00 [-9.89; -2.11]) in patients without diabetes.
GLP-1RAs result in mild reductions in SBP in patients with obesity.
In plain English: Efpeglenatide demonstrated significant reductions in FPG (MD = -1.53 mmol/L...), HbA1c (MD = -0.84...), body weight (MD = -2.24 kg...), and BMI (MD = -1.61 kg/m2...). However, efpeglenatide was associated with a moderate increase in the risk of gastrointestinal adverse events.
Qazi SU, Ansari HUH, Tharwani ZH, Altaf Z, Noman A, Ghazanfar S, Kumar S, Ansari HW, Nasir MM, Qazi S. · J Diabetes Metab Disord (2024)
Systematic review and meta-analysis (11 studies; random-effects) of efpeglenatide vs placebo in type 2 diabetes for cardiometabolic and safety outcomes
Pooled reductions: HbA1c -0.84%, fasting plasma glucose -1.53 mmol/L, body weight -2.24 kg, BMI -1.61 kg/m2 (all P<0.01)
Moderate increase in GI adverse events (nausea, diarrhea, vomiting); non-significant elevated hypoglycemia risk