Which therapies result in the greatest reductions in HbA1c and body weight? Which Therapies Result in the Greatest Reductions in HbA1c and Body Weight?

Infographic summary

Which therapies result in

the greatest reductions in

HbA1c and body weight?

A network meta-analysis of incretin-based therapies in patients with type 2 diabetes1,*

Study design1

The systematic review andnetwork meta-analysis included1,†:

26,490

patients withtype 2 diabetes

receiving incretin-based therapies

randomized controlled studies1

across

This promotional material by Eli Lilly and Company is for Healthcare Professionals in Germany, Spain, and Switzerland only. Country-specific prescribing information and adverse event reporting information can be found at the bottom of this infographic.

Study endpoints1

Primary endpoint:

Secondary endpoint:

Mean change from baseline in HbA1c1

Mean difference in change from baseline in FPG, PPG, BW, LDL cholesterol, SBP, DBP and prevalence of hypoglycemic events.1

Incretin-based treatment strategies included in the meta-analysis1

GLP-1 and GIP RA

GLP-1 monotherapy

GLP-1 combination treatment

Tirzepatide (▼Mounjaro®)

Semaglutide

GLP-1 RA plus basal insulin FRC (iGlarLixi, iDegLira)

Dulaglutide

GLP-1 RA plus SGLT2i combination

Efficacy results1

Which incretin-based treatment was the most efficacious in reducing HbA1c?1,*,‡

HbA1c

-2.00 -1.86 -1.63 -1.62 -1.60 -1.60 -1.52 -1.31 -1.25 -1.19 -1.11 -1.00 -0.90 -0.89 -0.46

[-2.22; -1.78] [-2.09; -1.63] [-1.87; -1.39] [-2.36; -0.88] [-1.88; -1.33] [-2.22; -0.98] [-1.82; -1.22] [-1.71; -0.91] [-1.87; -0.63] [-1.78; -0.59] [-1.51; -0.70] [-1.41; -0.59] [-1.16; -0.65] [-1.13; -0.64] [-0.86; -0.06]

HbA1c difference (%)

Comparison: other vs placebo (Random Effects Model)

95% CI

Treatment

-2.5

-2

-1.5

-1

-0.5

Tirzepatide 15 mg

Tirzepatide 10 mg

Tirzepatide 5 mg

Basal insulin + SU

iDegLira

Basal-bolus insulin

iGlarLixi

SGLT2i + GLP-1 RA

BlAsp 30

Semaglutide 2 mg

Dulaglutide 4.5 mg

Dulaglutide 3 mg

Basal insulin

GLP-1 RA

SGLT2i

Tirzepatide reduced HbA1c in a dose-dependent manner. Tirzepatide 15 mg emerged first in terms of HbA1c-lowering efficacy compared with other incretin-based therapies.1

Which incretin-based treatment was the most efficacious in reducing body weight?1,*,‡,§

-10.08 -8.27 -5.47 -5.45 -3.61 -3.53 -3.44 -3.16 -2.63 0.05 0.10 1.52 1.65 1.95 3.60

[-10.45; -9.72] [-8.66; -7.88] [-6.16; -4.79] [-5.85; -5.06] [-4.08; -3.15] [-4.36; -2.70] [-4.11; -2.77] [-3.62; -2.69] [-2.96; -2.29] [-0.37; 0.46] [-0.34; 0.54] [1.13; 1.91] [0.02; 3.27] [1.10; 2.79] [2.66; 4.54]

BW difference (kg)

Comparison: other vs placebo (Random Effects Model)

Treatment

95% CI

-10

-5

Basal-bolus insulin

BlAsp 30

Basal insulin + SU

Basal insulin

iDegLira

iGlarLixi

GLP-1 RA

Dulaglutide 3 mg

SGLT2i

Semaglutide 2 mg

Dulaglutide 4.5 mg

Tirzepatide 5 mg

SGLT2i + GLP-1 RA

Tirzepatide 10 mg

Tirzepatide 15 mg

Tirzepatide reduced body weight in a dose-dependent manner. Tirzepatide 15 mg emerged first in terms of efficacy for body weight reduction compared with other incretin-based therapies.1,§

Safety1

A similar rate of any AEs occurred in GLP-1 RA-based treatment strategies, with tirzepatide, high-dose GLP-1 RA, and GLP-1 RA plus SGLT2i combination displaying a similar risk of common GI side effects.1

How do these data from the meta-analysis link with clinical practice recommendations? The 2022 ADA/EASD consensus guideline states2:

Tirzepatide may be preferentially considered for the glycemic management of early stages of type 2 diabetes, to exploit its unparalleled weight reductions that may restore insulin secretion and action.1

CONCLUSION

Tirzepatide, a single molecule activating both GIP and GLP-1 receptors, provided the highest glucose-lowering efficacy across the meta-analysis.1

Tirzepatide, followed by GLP-1RA plus basal insulin FRC and GLP-1RA plusSGLT-2i combination, was associated with greater benefit on HbA1c than high dose GLP-1RA.1

Footnotes

Abbreviations and References

This content is promotional and has been developed and sponsored by Eli Lilly and Company. Intended for Healthcare Professionals only. Healthcare professionals can reduest the references from the company at any time Mounjaro® is a registered trademark of Eli Lilly and Company, its subsidiaries or affiliatesa © 2024 Eli Lilly and Company. All Rights Reserveda PP-LD-CH-0497/11.2024. PP-TR-ES-0836. PP-TR-DE-2167. December 2024

Indication and Safety Information

Indication and Safety Information Mounjaro is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise3 as monotherapy when metformin is considered inappropriate due to intolerance or contraindications in addition to other medicinal products for the treatment of diabetes. Registration conditions for Mounjaro may differ internationally. For indications, important safety information, and adverse event/product complaint information, please refer to you country's specific information at the end of this document.

Footnotes *This meta-analysis includes studies with diverse populations, interventions, and outcomes, which may affect the consistency of the findings. Differences in study design and methods could impact the reliability of treatment effects and limit the generalizability of the conclusions. As this meta-analysis is not based on head-to-head comparisons, caution is advised when interpreting the overall results.' †PubMed, MEDLINE, and Web of Science (from database inception to June 24, 2023) were searched for randomized controlled studies, published in English, that enrolled individuals with type 2 diabetes treated with tirzepatide, iGlarLixi, iDegLira, GLP-1 RA plus SGLTi combination, or high-dose GLP-1 RA (dulaglutide 3 mg and 4.5 mg, semaglutide 2 mg) compared with placebo or active comparators.' ‡Values represent mean difference from the network meta-analysis and 95% Cl. Treatments are presented according to their effect estimate compared with placebo.' §In SURPASS clinical trials, weight change was a secondary endpoint.3

Abbreviations and References ADA, American Diabetes Association; AE, adverse event; BIAsp 30, biphasic insulin aspart 30/70; BW, body weight; CI, confidence interval; EASD, European Association for the Study of Diabetes; FPG, fasting plasma glucose; FRC, fixed-ratio combination; Gl, gastrointestinal; GIP, glucose-dependent insulinotropic polypeptide; GLP-1, glucagon-like peptide-1; HbA1c, glycated hemoglobin; MD, mean difference; MOA, mechanism of action; PPG, post-prandial glucose; RA, receptor agonist; SGLT2i, sodium-glucose co-transporter-2 inhibitor; SU, sulphonylurea. References Caruso I et al. eClinicalMedicine. 2023;64:102181. Davies MJ et al. Diabetes Care. 2022;45(11):2753–86. Eurpean Medicines Agency. Mounjaro (tirzepatide) summary of product characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/mounjaro-epar-product-information_en.pdf. Last accessed: 20 December 2024.

Switzerland Eli Lilly (Suisse) SA, Chemin des Coquelicots 16, 1214 Vernier. www.lilly.ch Click here for the prescribing information: www.swissmedicinfo.ch Spain ▼ Este medicamento está sujeto a seguimiento adicional, es prioritaria la notificación de sospechas de reacciones adversas asociadas a este medicamento. Prescribing information document La dosis de Mounjaro® de 15 mg no está comercializada en España en este momento. Los fármacos TZP15mg, Dula 3.0 y 4.5mg, iDegLira, iGlarLixi y sema 2.0 no están comercializados en este momento en España. Germany Mounjaro® (Tirzepatid) ist angezeigt zur Behandlung von Erwachsenen mit unzureichend eingestelltem Typ-2-Diabetes als Ergänzung zu Diät und Bewegung als Monotherapie, wenn die Einnahme von Metformin wegen Unverträglichkeiten oder Kontraindikationen nicht angezeigt ist, zusätzlich zu anderen Arzneimitteln zur Behandlung von Diabetes mellitus; sowie als Ergänzung zu einer kalorienreduzierten Diät und erhöhter körperlicher Aktivität zum Gewichtsmanagement, einschließlich Gewichtsabnahme und Gewichtserhaltung, bei Erwachsenen mit einem Ausgangs-BMI von ≥ 30 kg/m2 (Adipositas) oder ≥ 27 kg/m2 bis < 30 kg/m2 (Übergewicht) bei Vorliegen mindestens einer gewichtsbedingten Begleiterkrankung (z. B.Hypertonie, Dyslipidämie, obstruktive Schlafapnoe, Herz-Kreislauf-Erkrankung, Prädiabetes oder Typ-2-Diabetesmellitus).1 Trulicity ist angezeigt zur Behandlung von Patienten ab 10 Jahren mit unzureichend kontrolliertem Typ 2-Diabetes mellitus unterstützend zu Diät und Bewegung: als Monotherapie, wenn die Einnahme von Metformin wegen Unverträglichkeit oder Kontraindikationen nicht angezeigt ist. zusätzlich zu anderen Arzneimitteln zur Behandlung des Diabetes mellitus? Mounjaro® Fachinformation, aktueller Stand. Mounjaro® Trulicity Fachinformation, aktueller Stand: Trulicity®

Modified from Caruso I, et al. 20231