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Tir7.8
Tirzepatide – Forschung
Überwiegend Mechanismus / Beobachtung
48 begutachtete Studien
Was die Evidenz sagt
Überwiegend Mechanismus / Beobachtung
Die meisten Studien zu Tirzepatide 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 2021–2026 mit einer typischen Studiengröße von 1,995 Teilnehmenden.
Basierend auf 48 Studien · 19 Meta-Analysen · 16 RCTs · 453,129 Teilnehmende insgesamt
Konfidenz
Hohe Konfidenz
Nach Outcome
Weight managementDurchschnittliche Gewichtsreduktionen von bis zu ~21 % über 72 Wochen in Adipositas-Studien — die höchste aller bislang zugelassenen Medikamente zur Gewichtsreduktion, im direkten Vergleich Semaglutid überlegen · Monate (Dosis über ~20 Wochen auftitriert)
Überwiegend Mechanismus / Beobachtung35 Studien
Glycemic & metabolic controlSenkt den HbA1c-Wert in Phase-3-Diabetesstudien um etwa 1,9–2,6 Prozentpunkte; im direkten Vergleich Basalinsulin und Semaglutid 1 mg überlegen · Wochen bis Monate · Kombinierter starker Gewichtsverlust und ausgeprägte glykämische Kontrolle verbessern den allgemeinen Stoffwechselstatus · Monate
Überwiegend Mechanismus / Beobachtung20 Studien
Safety profile
Überwiegend Mechanismus / Beobachtung17 Studien
Heart & blood pressure
Überwiegend Mechanismus / Beobachtung10 Studien
Sleep apnea & respiratory
Überwiegend Mechanismus / Beobachtung3 Studien
Aktives Forschungsgebiet
48 Studien in den letzten 5 Jahren · Neueste Meta-Analyse: 2026
20212026
1Meta-Analysen=199,877 · very large study2026
Further prospective trials are needed to clarify causal mechanisms and inform clinical decision-making.
Liang CS et al. · International journal of molecular sciences (2026)
Odds ratios (ORs) with 95% credible intervals (CrIs) were calculated, and surface under the cumulative ranking curves (SUCRA) were used to estimate relative safety rankings.
Only high-dose tirzepatide (10-15 mg/week) was associated with a significantly increased risk of AKI compared to controls (absolute risk difference: 0.28%; number needed to harm: 357).
Funding World Health Organization (WHO) REGISTRATION: Protocol (2022) DOI: 10.1002/14651858.CD015092 Updated Protocol (2025): PROSPERO CRD420250654193.
Franco JV, Guo Y, Varela LB, Aqra Z, Alhalahla M, Medina Rodriguez M, Salvador Oscco EL, Patiño Araujo B, Banda S, Escobar Liquitay CM, Bracchiglione J, Meza N, Madrid E. · The Cochrane database of systematic reviews (2025)
Tirzepatide may result in an increase in non-serious adverse events (RR 1.33, 95% CI 1.03 to 1.71; 5 studies, 4582 participants; low-certainty evidence).
The evidence is very uncertain about the effect on serious adverse events (RR 0.99, 95% CI 0.88 to 1.12; 8 studies, 6359 participants; very low-certainty evidence).
Tirzepatide may result in little to no difference in adverse events leading to withdrawal (RR 2.06, 95% CI 1.21 to 3.52; 8 studies, 6359 participants; low-certainty evidence).
The use of GLP-1 RAs is significantly associated with an increased risk of hair loss.
Cheng PL et al. · Diabetes research and clinical practice (2026)
The pooled analysis revealed a significantly higher risk of hair loss in GLP-1 RA users than in placebo users (risk ratio [RR]: 3.252; 95% confidence interval [CI]: 1.437 to 7.358).
The significant results persisted even when the analysis was restricted to RCTs focusing on patients with overweight or obesity (RR: 3.587; 95% CI: 2.100 to 6.124).
Furthermore, a single-arm analysis revealed that the event rate of hair loss following GLP-1 RA therapy was 3.9%.
Among people with type 2 diabetes and atherosclerotic cardiovascular disease, tirzepatide was associated with a reduced risk of major kidney events compared with dulaglutide, primarily driven by a reduction in new-onset macroalbuminuria in people with low-to-moderate-risk chronic kidney disease, and slowed decline in kidney function in people with high-risk chronic kidney disease.
Zoungas S et al. · The lancet. Diabetes & endocrinology (2026)
Clinical trial examining Tirzepatide efficacy
Published in The lancet. Diabetes & endocrinology (2026)
Precision remains limited; clinicians should maintain vigilance, optimise modifiable risks, individualise dosing, and contribute to post-marketing surveillance.
Benny O, Agarwal A, Alecock H, Subramani RG, Pawar A, Shams Z, Kermansaravi M, Pouwels S, Yang W, Obi CG, Cripps P, Tang A, Gelber E, Lala A, Nadi K, Mahmoud A, Hammoda M, Al-Sarireh H, Egan R, Hanratty D, Drummond A, Caplin S, Harris D, Barry J, Beamish A, Al-Ardah M, Al-Sarireh B, Sum Ong SC, Hajibandeh S, Honey JR, Dababneh A, Ribordy V, Hautz WE, Jakob D, Patel B, Sprackling I, Ashabi A, Kambal A, Oviedo RJ, Parmar C, Mowbray N, Al Hadad M, Gawdat K, Hoffmann R, Hakky S, Al-Sarireh A, Nowak MA, Shikora S, Ahmed AR, Ahmad SJ. · Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] (2026)
Acute pancreatitis was exceedingly rare (0.22%).
Head-to-head dose comparisons showed no significant differences: 10 mg vs 5 mg (RR 0.78, 95% CI 0.29-2.09), 15 mg vs 5 mg (RR 0.70, 0.27-1.82), and 15 mg vs 10 mg (RR 1.13, 0.42-3.02); sensitivity analyses were concordant.
Most RoB 2.0 domains were low risk, with some concerns for missing data/selective reporting.
Both MBS and GLP-1 RAs provide substantial metabolic benefits.
Sabatella L et al. · Obesity (Silver Spring, Md.) (2026)
At < 104 weeks, MBS achieved greater reductions than GLP-1 RAs in %TWL (ETD -10.3%; p = 0.001), BMI (-4.5 kg/m2; p < 0.001), body weight (-11.7 kg; p < 0.001), waist circumference (-12.6 cm; p < 0.001), and HbA1c (-0.5%; p = 0.033).
At ≥ 104 weeks, differences remained for %TWL (-9.1%; p = 0.022) and body weight (-14.6 kg; p = 0.049).
Among participants with type 2 diabetes, MBS produced greater reductions in BMI, weight, waist, and %TWL, with similar HbA1c improvement.
In this post hoc analysis, the dual GLP-1 and GIP agonist tirzepatide, compared with the GLP-1 agonist dulaglutide, was associated with a lower incidence of a broad 6-component composite cardiovascular and kidney end point in patients with diabetes and established cardiovascular disease.
Nissen SE et al. · JAMA cardiology (2026)
Among the 13 165 patients enrolled, the mean (SD) age was 64 (8.8) years; 9348 patients (71.0%) were male and 3817 were female (29.0%).
The mean (SD) hemoglobin A1c was 8.4% (0.93).
After a median (IQR) treatment duration of 46.9 (34.6-50.6) months, the primary cardiorenal end point occurred in 1559 tirzepatide-treated patients (23.7%) and 1803 dulaglutide-treated patients (27.4%; hazard ratio [HR], 0.84; 95% CI, 0.79-0.90; P < .001).
Due to the limited number of trials for tirzepatide and lanifibranor, further large-scale studies are warranted to confirm their role in MASLD/MASH management.
Zhao S et al. · Internal and emergency medicine (2026)
The analysis included 2497 individuals (1112 [45%] male, mean age 55.6 years [SD 11.6], mean BMI 35.3 kg/m2 [SD 6.3], and 1385 [55%] with diabetes).
Tirzepatide (mean difference [MD] - 34.90% [95% CI: - 53.31 to - 16.49]) and resmetirom (MD - 31.45% [95% CI: - 35.93 to - 26.97]) significantly reduced hepatic steatosis as assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF).
Tirzepatide significantly reduced serum aminotransferase levels (ALT: MD - 30.90%, p < 0.00001; AST: MD - 20.71%, p < 0.00001).
Sillassen CDB, Faltermeier P, Bjerg JL, Andersen RK, Petersen JJ, Andersen PB, Kamp CB, Karlsson F, Grand J, Dominguez H, Frølich A, Gæde P, Gluud C, Mathiesen O, Jakobsen JC. · BMC medicine (2026)
A meta-analysis of all-cause mortality showed no evidence of a difference; however, this finding was based on sparse data and is associated with very low certainty.
Tirzepatide use is associated with an increased risk of several gastrointestinal nsAEs.
Further trials designed for investigating the effects of tirzepatide compared with placebo on all-cause mortality are needed.
These findings suggest tirzepatide enhances perceived physical capacity and quality of life, although the extremely high between-study heterogeneity limits the interpretability of pooled estimates and warrants cautious interpretation.
Schmidt PHS, de Souza VSN, Machado LG, Rodrigues JVA, da Cruz JVR, de Souza LSN, Dos Santos BE, Hohl A, Ronsoni MF, van de Sande-Lee S. · Diabetes, obesity & metabolism (2026)
Random-effects models were used to calculate pooled mean differences (MD) with 95% confidence intervals (CI).
Tirzepatide significantly improved physical function compared with placebo, both in SF-36 physical function (MD 2.26 points; 95% CI, 1.76-2.76; I 2 = 99.8%; p < 0.001) and IWQOL-Lite-CT physical function (MD 10.10 points; 95% CI, 8.61-11.60; I 2 = 99.8%; p < 0.001).
Conclusions Tirzepatide 10 and 15 mg once weekly significantly improve patient-reported physical function in adults with overweight or obesity.
Conclusion In patients with cardiovascular or renal disease, GLP-1RAs and tirzepatide provide consistent cardiovascular and renal protection, with a possible benefit in reducing hospitalization for heart failure among individuals with obesity.
Zhang J, Guan X, Kong M, Xia M, Yu Y, Zhang C. · Metabolism: clinical and experimental (2026)
GLP-1RAs significantly reduced the risk of the primary composite outcome (RR 0.88, 95 % CI 0.84-0.91, P < 0.001).
GLP-1RAs and tirzepatide also significantly reduced the risk of death from any cause (RR 0.88, 95 % CI 0.84-0.92, P < 0.001), and death from cardiovascular causes (RR 0.88, 95 % CI 0.83-0.93, P < 0.001).
Although the overall effect of GLP-1RAs on hospitalization for heart failure was not statistically significant (RR 0.92, 95 % CI 0.78-1.08), a potential benefit was observed in obese patients (P for interaction = 0.02), warranting further investigation.
The evidence suggests that semaglutide and tirzepatide result in weight reduction in patients with RWG after MBS.
Osorio Manyari AA, Armas Alvarez AL, Osorio Manyari JD, Onieva Gonzalez F, Pouwels S. · Obesity surgery (2025)
Fifteen to forty% of patients experience recurrent weight gain (RWG) after metabolic bariatric surgery (MBS).
The percentage total weight loss (%TWL) was - 10.97% [95% CI, - 13.41 to - 8.53; p < 0.05] for semaglutide and - 13.63% [95% CI, - 22.59 to - 4.67; p < 0.05] for tirzepatide.
To assess the effects of semaglutide and tirzepatide after MBS, we conducted a meta-analysis of data from inception to August 2025.
Conclusions Compared with placebo, tirzepatide resulted in statistically significant and clinically meaningful weight reduction, especially in patients without diabetes (with overweight/obesity), with an acceptable safety profile.
Cerchi E, Santo PADE, de Oliveira MC, Janovsky CCPS, Halpern B. · International journal of obesity (2005) (2025)
For each subpopulation analysis, the random-effects model was used to calculate pooled risk ratios (RRs) and mean differences (MDs), with their 95% confidence intervals, for dichotomous and continuous endpoints, respectively.
Statistical significance was considered at p < 0.05.
Compared with placebo, tirzepatide led to significantly greater relative and absolute weight reductions in patients with (RR -9.54%, p < 0.01; MD -9.06 kg, p < 0.01) and without diabetes (RR -17.15%, p < 0.01; MD -18.11 kg, p < 0.01).
The least-squares mean percent change in weight at week 72 was -20.2%... with tirzepatide and -13.7%... with semaglutide (P<0.001).
Aronne LJ, Horn DB, le Roux CW, Ho W, Falcon BL, Gomez Valderas E, Das S, Lee CJ, Glass LC, Senyucel C, Dunn JP; SURMOUNT-5 Trial Investigators. · N Engl J Med (2025)
Phase-3b open-label head-to-head RCT (SURMOUNT-5) in 751 adults with obesity but without diabetes, max-tolerated tirzepatide vs max-tolerated semaglutide
Weight loss -20.2% with tirzepatide vs -13.7% with semaglutide at 72 weeks — tirzepatide superior
Greater waist-circumference reduction with tirzepatide (-18.4 vs -13.0 cm)
Among persons with moderate-to-severe obstructive sleep apnea and obesity, tirzepatide reduced the AHI, body weight, hypoxic burden, hsCRP concentration, and systolic blood pressure.
Malhotra A, Grunstein RR, Fietze I, Weaver TE, Redline S, Azarbarzin A, Sands SA, Schwab RJ, Dunn JP, Chakladar S, Bunck MC, Bednarik J; SURMOUNT-OSA Investigators. · N Engl J Med (2024)
Two 52-week phase-3 double-blind RCTs (SURMOUNT-OSA) in obese adults with moderate-to-severe OSA, off and on PAP therapy
Apnea-hypopnea index fell by an estimated 20.0 events/hour (trial 1) and 23.8 events/hour (trial 2) more than placebo
Also improved body weight, hypoxic burden, hsCRP, and systolic blood pressure
Tirzepatide treatment was not associated with excess cardiovascular risk.
Del Prato S, Kahn SE, Pavo I, Weerakkody GJ, Yang Z, Doupis J, Aizenberg D, Wynne AG, Riesmeyer JS, Heine RJ, Wiese RJ; SURPASS-4 Investigators. · Lancet (2021)
Phase-3 open-label RCT (SURPASS-4) in 1995 adults with type 2 diabetes and high cardiovascular risk, tirzepatide 5/10/15 mg vs titrated insulin glargine
HbA1c reductions of -2.43% (10 mg) and -2.58% (15 mg) vs -1.44% glargine
Adjudicated MACE not increased on tirzepatide (HR 0.74, 95% CI 0.51-1.08); lower hypoglycemia than glargine