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Efp4.3
Efpeglenatid – Forschung
Überwiegend Mechanismus / Beobachtung
7 begutachtete Studien
Was die Evidenz sagt
Überwiegend Mechanismus / Beobachtung
Die meisten Studien zu Efpeglenatid sind mechanistisch oder beobachtend statt RCTs, die einen klinischen Effekt messen — betrachte die Ergebnisse als vorläufig.
Die meiste Evidenz stammt aus hochwertigen Meta-Analysen und randomisierten Studien, veröffentlicht 2019–2024 mit einer typischen Studiengröße von 3,983 Teilnehmenden.
Basierend auf 7 Studien · 2 Meta-Analysen · 4 RCTs · 36,108 Teilnehmende insgesamt
Konfidenz
Hohe Konfidenz
Nach Outcome
Glycemic controlDosisabhängige HbA1c-Senkungen über das gesamte Programm; gepoolte Metaanalyse HbA1c -0,84 % gegenüber Placebo · Wochen bis Monate
Überwiegend Mechanismus / Beobachtung7 Studien
Safety profile
Überwiegend Mechanismus / Beobachtung6 Studien
Weight & body compositionBei Adipositas ohne Diabetes placebobereinigter Gewichtsverlust von ~6,3-7,2 kg über 20 Wochen (Phase 2) · Monate (titriert)
Überwiegend Mechanismus / Beobachtung5 Studien
Cardiovascular & renal outcomesAMPLITUDE-O senkte den primären MACE-Komposit-Endpunkt um 27 % gegenüber Placebo (HR 0,73) bei Hochrisiko-Typ-2-Diabetes · Über ~1,8 Jahre
Zu wenige bewertete Studien2 Studien
Aktives Forschungsgebiet
5 Studien in den letzten 5 Jahren · Neueste Meta-Analyse: 2024
20192024
1RCTn=4,076 · very large study2021
An incident MACE occurred in 189 participants (7.0%) assigned to receive efpeglenatide... and 125 participants (9.2%) assigned to receive placebo... (hazard ratio, 0.73; 95% confidence interval [CI], 0.58 to 0.92; P<0.001 for noninferiority; P = 0.007 for superiority). A composite renal outcome event... occurred in 353 participants (13.0%)... and in 250 participants (18.4%)... (hazard ratio, 0.68; 95% CI, 0.57 to 0.79; P<0.001).
Gerstein HC, Sattar N, Rosenstock J, Ramasundarahettige C, Pratley R, Lopes RD, Lam CSP, Khurmi NS, Heenan L, Del Prato S, Dyal L, Branch K; AMPLITUDE-O Trial Investigators. · N Engl J Med (2021)
Pivotal randomized, placebo-controlled cardiovascular-outcomes trial (n=4,076) at 344 sites in 28 countries, in type 2 diabetes with a history of cardiovascular disease OR current kidney disease plus another risk factor; weekly subcutaneous efpeglenatide 4 or 6 mg vs placebo, median follow-up 1.81 years
Primary MACE (nonfatal MI, nonfatal stroke, CV/undetermined death) reduced 27% (HR 0.73; P=0.007 for superiority) — the first EXENDIN-based GLP-1 agonist shown to lower cardiovascular events
Composite kidney outcome (decreased kidney function or new macroalbuminuria) reduced 32% (HR 0.68; P<0.001)
Least squares mean HbA1c reductions from baseline were statistically superior for each efpeglenatide dose versus placebo (2 mg, -0.5%...; 4 mg, -0.8%...; 6 mg, -1.0% [95% CI -1.4, -0.7; P < 0.0001]).
Frias JP, Choi J, Rosenstock J, Popescu L, Niemoeller E, Muehlen-Bartmer I, Baek S. · Diabetes Care (2022)
Phase-3 double-blind, placebo-controlled monotherapy RCT in type 2 diabetes inadequately controlled with diet and exercise; once-weekly efpeglenatide 2/4/6 mg vs placebo for up to 56 weeks
All doses superior to placebo on HbA1c at week 30 (placebo-adjusted up to -1.0%), reaching HbA1c ~6.4-6.9% from a baseline of 8.1%
Significant reductions in body weight and fasting plasma glucose at the 4 and 6 mg doses vs placebo
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 ≥1 mg lowered HbA1c by a placebo-adjusted 0.6-1.2% to a final HbA1c of 6.3-6.8%; the 4 mg dose was noninferior to liraglutide
Greater weight loss with 3 and 4 mg vs placebo (placebo-adjusted -1.4 and -2.0 kg); no neutralizing antibodies detected
Over 20 wk, all doses of efpeglenatide significantly reduced body weight from baseline versus placebo (P < 0.0001), with placebo-adjusted reductions ranging between -6.3 kg (6 mg once every 2 wk) and -7.2 kg (6 mg once weekly).
Pratley RE, Kang J, Trautmann ME, Hompesch M, Han O, Stewart J, Sorli CH, Jacob S, Yoon KH. · Diabetes Obes Metab (2019)
Phase-2, randomized, double-blind, placebo-controlled weight-management trial in adults WITHOUT diabetes (BMI ≥30, or ≥27 with comorbidity); efpeglenatide 4/6 mg weekly or 6/8 mg every 2 weeks vs placebo plus hypocaloric diet (n=297) over 20 weeks
Placebo-adjusted weight loss of -6.3 to -7.2 kg; more participants achieved ≥5% or ≥10% loss vs placebo
Improved glycemic variables and lipid profile (cholesterol, triglycerides) vs placebo
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 point estimate was ~-3.2 kg, placing it within the class but below high-dose semaglutide and liraglutide
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
Efpeglenatide's effect on both outcomes did not vary with any kidney disease measure (all interaction p values ≥0.26)... The beneficial effect of efpeglenatide on these outcomes is independent of kidney-related risk category.
Prespecified epidemiological analysis of AMPLITUDE-O data (n=3,983 with baseline eGFR/UACR) relating kidney-disease indices to MACE and the composite kidney outcome and testing whether efpeglenatide's effect varies with them
Baseline eGFR, UACR and KDIGO category were strong, independent determinants of both cardiovascular and kidney events (e.g. ~18-fold kidney-outcome hazard for the highest vs lowest UACR third)
Efpeglenatide's cardiorenal benefit was consistent across the full spectrum of baseline kidney disease (all interaction p≥0.26)
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