How does the efficacy of different therapies compare across patient subgroups How Does the Efficacy of Different Therapies Compare Across Patient Subgroups?

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.

Primary endpoint:

Mean change from baseline in HbA1c1

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

Subgroup analysis: BMI1

HbA1c reduction in patients withbaseline BMI ≥30 kg/m2 subgroup1,*,‡

Patientsubgroup1:BMI≥30 kg/m2

-2.08 -1.89 -1.68 -1.67 -1.68 -1.55 -1.53 -1.41 -1.27 -1.16 -1.11 -1.09 -0.68

[-2.35; -1.80] [-2.18; -1.60] [-2.02; -1.34] [-1.95; -1.38] [-2.36; -1.00] [-1.95; -1.16] [-1.97; -1.09] [-2.06; -0.76] [-1.71; -0.83] [-1.60; -0.72] [-1.40; -0.83] [-1.40; -0.78] [-1.12; -0.25]

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

iDegLira

Tirzepatide 5 mg

Bolus insulin

iGlarLixi

SGLT2i + GLP-1 RA

Semaglutide 2 mg

Dulaglutide 4.5 mg

Dulaglutide 3 mg

Basal insulin

GLP-1 RA

SGLT2i

Safety Information

Footnotes

Abbreviations and References

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.1 †PubMed, MEDLINE, and Web of Science (from database inception to June 24, 2023) were searched for randomised controlled studies, published in English, that enrolled individuals with type 2 diabetes treated with tirzepatide, iGlarLixi, iDegLira, GLP-1 RA plus SGLT2i combination, or high-dose GLP-1 RA (dulaglutide 3 mg and 4.5 mg, semaglutide 2 mg) compared with placebo or active comparators.1 ‡ Values represent mean difference from the network meta-analysis and 95% CI. Treatments are presented according to their effect estimate compared with placebo. The graph showcases significant results only.1 §Values represent mean difference from the network meta-analysis and 95% CI. Treatments are presented according to their effect estimate compared with a GLP-1 RA. The graph showcases significant results only.1 ¶In SURPASS clinical trials, weight change was a secondary endpoint.2

Safety Information Mounjaro is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exerciseª 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.

Abbreviations and References ADA, American Diabetes Association; BIAsp 30, biphasic insulin aspart 30/70; BMI, body mass index; CI, confidence interval; EASD, European Association for the Study of Diabetes; FRC, fixed-ratio combination; GIP, glucose-dependent insulinotropic polypeptide; GLP-1, glucagon-like peptide-1; HbA1c, glycated hemoglobin; MD, mean difference; RA, receptor agonist; SGLT2i, sodium-glucose co-transporter-2 inhibitor; SU, sulphonylurea. References Caruso I, et al. eClinicalMedicine 2023;64:102181. Mounjaro (tirzepatide). Summary of Product Characteristics. Davies MJ, et al. Diabetes Care 2022;45(11):2753–86. ElSayed NA, et al. Diabetes Care 2023;46(Suppl 1):S140–57.

This content is promotional and has been developed and sponsored by Eli Lilly and Company. Intended for Healthcare Professionals only. Healthcare professionals can request the references from the company at any time. Mounjaro® is a registered trademark of Eli Lilly and Company, its subsidiaries or affiliates.© 2024 Eli Lilly and Company. All Rights Reserved.PP-TR-CH-0605/11.2024. PP-TR-ES-0764. PP-TR-DE-2168. November 2024

Subgroup analyses for change from baseline in HbA1c included1:

BMI (<30 kg/m2, ≥30 kg/m2)

Ethnicity (Asian/mixed)

Duration of type 2 diabetes (<10 years/≥10 years)

Efficacy results across patient subgroups with type 2 diabetes1

The results for reductions in HbA1c in the primary analysis for incretin-based treatment strategies were mostly confirmed in patient subgroups. Tirzepatide HbA1c reductions were similar regardless of baseline BMI and patients’ ethnicity.1

HbA1c reduction in patients withbaseline BMI <30 kg/m2 subgroup1,*,‡

-1.60-1.53-1.25-0.97-0.90-0.87

[-1.98; -1.22][-1.91; -1.51][-1.68; -0.82][-1.74; -0.20][-1.40; -0.40][-1.37; -0.37]

HbA1c difference (%)

Comparison: other vs placebo (Random Effects Model)

Treatment

95% CI

-2.5

-2

-1.5

-1

-0.5

iGlarLixi

Basal insulin + SU

Tirzepatide 5 mg

iDegLira

Tirzepatide 10 mg

Tirzepatide 15 mg

Patientsubgroup1:BMI<30 kg/m2

Subgroup analysis: Ethnicity1

Patientsubgroup1:Asianpatients

HbA1c reduction in Asian patients1,*,§

-1.50 -1.49 -1.22 -0.95 -0.88 -0.85 -0.11

[-1.93; -1.24] [-1.84; -1.15] [-1.57; -0.88] [-1.61; -0.29] [-1.15; -0.61] [-1.10; -0.59] [-0.33; 0.11]

Comparison: other vs GLP-1 RA(Random Effects Model)

Treatment

95% CI

iDegLira

Basal insulin + SU

Tirzepatide 5 mg

Tirzepatide 10 mg

Tirzepatide 15 mg

Basal insulin

iGlarLixi

-2.5

-2

-1.5

-1

-0.5

0.5

Among Asianpatients withtype 2 diabetes,all dosages oftirzepatide achievedthe greatestreduction in HbA1ccompared with otherincretin-basedtherapies.1,*

HbA1c reduction in the mixed ethnicity subgroup of patients1,*,‡

Patientsubgroup1:Mixedethnicities

-1.96 -1.81 -1.62 -1.62 -1.58 -1.48 -1.45 -1.34 -1.21 -1.21 -1.11 -1.04 -1.01 -0.61

[-2.20; -1.73] [-2.05; -1.56] [-1.93; -1.31] [-2.26; -0.98] [-1.84; -1.33] [-1.84; -1.12] [-1.86; -1.04] [-1.94; -0.73] [-1.63; -0.80] [-1.86; -0.56] [-1.52; -0.70] [-1.30; -0.77] [-1.29; -0.73] [-1.01; -0.20]

Comparison: other vs placebo (Random Effects Model)

Treatment

95% CI

-2.5

-2

-1.5

-1

-0.5

0.5

Tirzepatide 10 mg and 15 mg achieved the greatest reduction in HbA1c compared with other incretin-based therapies among a mixed ethnicity subgroup of patients with type 2 diabetes. Tirzepatide 5 mg achieved greaterreductions in HbA1c than semaglutide anddulaglutide in mixedethnicity patients withtype 2 diabetes.1,*

SGLT2i

GLP-1 RA

Basal insulin

Dulaglutide 3 mg

BIAsp 30

Dulaglutide 4.5 mg

Semaglutide 2 mg

SGLT2i + GLP-1 RA

iGlarLixi

Tirzepatide 5 mg

iDegLira

Tirzepatide 10 mg

Tirzepatide 15 mg

Basal insulin + SU

HbA1c difference (%)

Subgroup analysis: Type 2 diabetes duration1

HbA1c reduction in patients withtype 2 diabetes duration <10 years1,*,‡

-2.07 -1.92 -1.68 -1.54 -1.38 -1.29 -1.15 -1.08 -0.97 -0.95 -0.85 -0.44

[-2.36; -1.78] [-2.22; -1.62] [-1.98; -1.38] [-1.90; -1.17] [-1.71; -1.05] [-1.71; -0.86] [-1.76; -0.54] [-1.50; -0.66] [-1.39; -0.55] [-1.25; -0.64] [-1.13; -0.56] [-0.86; -0.02]

HbA1c difference (%)

Comparison: other vs placebo (Random Effects Model)

Treatment

95% CI

-2.5

-2

-1.5

-1

-0.5

SGLT2i

Basal insulin

GLP-1 RA

Dulaglutide 3 mg

Dulaglutide 4.5 mg

Semaglutide 2 mg

SGLT2i + GLP-1 RA

iGlarLixi

Tirzepatide 5 mg

iDegLira

Tirzepatide 10 mg

Tirzepatide 15 mg

Patientsubgroup1:diseaseduration<10 years

HbA1c reduction in patients withtype 2 diabetes duration ≥10 years1,*,‡

-2.48 -2.48 -2.31 -2.21 -2.16 -2.00 -1.94 -1.89 -1.80 -1.46

[-3.17; -1.79] [-3.47; -1.50] [-3.39; -1.22] [-2.93; -1.48] [-2.61; -1.72] [-2.45; -1.54] [-2.94; -0.93] [-2.62; -1.17] [-2.33; -1.27] [-2.09; -0.83]

HbA1c difference (%)

Comparison: other vs placebo (Random Effects Model)

Treatment

95% CI

-4

Patientsubgroup1:diseaseduration ≥10 years

Basal insulin

Tirzepatide 5 mg

GLP-1 RA

BIAsp 30

Tirzepatide 10 mg

Tirzepatide 15 mg

Basal insulin + SU

iGlarLixi

Basal-bolus insulin

iDegLira

-3.5

-3

-2.5

-2

-1.5

-1

-0.5

In patients with diabetes for fewer than 10 years, all dosages of tirzepatide achieved the greatest reductions in HbA1c compared with other incretin-based strategies.1,*

Tirzepatide's role in early-stage Type 2 diabetes

Patient with early-stage type 2 diabetes (diagnosed within 10 years)

HbA1c

The network meta-analysis suggested that tirzepatide should beconsidered in patients with early-stage type 2 diabetes (diagnosedwithin 10 years) to exploit its unparalleled weight-lowering effectthat could be beneficial for restoring insulin secretion and action.1,§

How do these data from the meta-analysis linkwith clinical practice recommendations?

Individualizing carein type 2 diabetes3

CONCLUSION

In patients with BMI ≥30 kg/m2, tirzepatide 15 mg and 10 mg, followed by iDegLira and tirzepatide 5 mg, achieved the greatest HbA1c reduction.1,*

Target reductions in bothHbA1c and body weight4

Individualized and person-centered care is recommended by the ADA/EASD Consensus to help patients integrate diabetes care into their lives.3

When selecting a glucose-lowering treatment strategy, the ADA/EASD recommend a regimen with high to very high dual glucose and weight efficacy, and tirzepatide is recommended for very high efficacy in achieving weight loss.4,¶

Infographic summary

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

across patient subgroups?

different therapies compare

How does the efficacy of

Modified from Caruso I, et al. 20231

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) odert ≥ 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-Diabetes mellitus).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.² 1. Mounjaro® Fachinformation, aktueller Stand. Mounjaro® 2. Trulicity Fachinformation, aktueller Stand: Trulicity®

Modified from Caruso I, et al. 20231

In patients with BMI <30 kg/m2, all dosages of tirzepatide achieved the greatest HbA1c reduction.1,*

Among Asian patients with type 2 diabetes, all dosages of tirzepatide achieved the greatest reduction in HbA1c compared with other incretin-based therapies.1,*

Among a mixed ethnicity subgroup of patients with type 2 diabetes, tirzepatide 10 mg and 15 mg achieved the greatest reduction in HbA1c compared with other incretin-based therapies.1,*

HbA1c difference (%)