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Cited by 56Diabetes Treatment and ManagementDiabetes Management and ResearchPharmacology and Obesity Treatment

Efficacy of tirzepatide 5, 10 and 15 mg versus semaglutide 2 mg in patients with type 2 diabetes: An adjusted indirect treatment comparison

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Vadher, Karan, Patel, Hiren, Mody, Reema, Levine, Joshua A., Hoog, Meredith, Cheng, Alice YY., Pantalone, Kevin M., Sapin, Hélène·2022·Diabetes, Obesity and Metabolism
DOI 10.1111/dom.14775PMC PMC9546430
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Abstract

Aim: To conduct an adjusted indirect treatment comparison (aITC) of the efficacy of tirzepatide 5/10/15 mg versus semaglutide 2 mg in patients with type 2 diabetes. Materials and Methods: The primary analysis was a Bucher aITC of the change from baseline at week 40 in HbA1c (%) and body weight (kg). Aggregate data from the SURPASS‐2 study that met the HbA1c inclusion criterion of the SUSTAIN FORTE study and from SUSTAIN FORTE metformin‐only treated patients were used for primary analysis. Results: The SURPASS‐2 refined population comprised 238/245/240 and 240 participants for tirzepatide 5/10/15 mg and semaglutide 1 mg, respectively. The SUSTAIN FORTE metformin‐only population comprised 222 and 227 participants for semaglutide 1 and 2 mg, respectively. In this aITC, tirzepatide 10 and 15 mg significantly reduced HbA1c versus semaglutide 2 mg with an estimated treatment difference (ETD) of −0.36% (95% confidence interval [CI] −0.63, −0.09) and −0.4% (95% CI −0.67, −0.13), respectively. Tirzepatide 10 and 15 mg significantly reduced body weight versus semaglutide 2 mg with an ETD of −3.15 kg (95% CI −4.84, −1.46) and −5.15 kg (95% CI −6.85, −3.45), respectively. There were no significant differences between tirzepatide 5 mg and semaglutide 2 mg on change from baseline in HbA1c and body weight. Conclusions: In this aITC, HbA1c and weight reductions were significantly greater for tirzepatide 10 and 15 mg versus semaglutide 2 mg and were similar for tirzepatide 5 mg versus semaglutide 2 mg. These findings provide comparative effectiveness insights in the absence of a head‐to‐head clinical trial.

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  • The average HbA1c reduction with GLP-1RA in MASLD studies was estimated to be 0.5% in individuals with and without type 2 diabetes but may be substantially higher depending on the investigated compound and collective.

    “The average HbA1c reduction with GLP-1RA in MASLD studies was estimated to be 0.5 % in individuals with and without type 2 diabetes [104] but may be substantially higher depending on the investigated compound and collective [105].”

    From Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease? (2024) · cites this paper as [105]

    Citation [105] attaches to the possibility of larger HbA1c reductions, not the preceding 0.5% estimate attributed to [104]. The Results (page unavailable) report that tirzepatide 10 and 15 mg reduced HbA1c more than semaglutide 2 mg, supporting a compound-dependent difference. The comparison was confined to patients with type 2 diabetes; it does not establish how reductions vary in MASLD populations or people without diabetes. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Recent RCTs with tirzepatide suggest superior effects on glycemic control and weight loss compared to semaglutide.

    “Recent results from RCTs with tirzepatide suggest superior effects on glycemic control and weight loss compared to semaglutide [105,116] and a first cardiovascular risk assessment importantly also indicated no increased risk of MACE [123].”

    From Obesity and MASLD: Is weight loss the (only) key to treat metabolic liver disease? (2024) · cites this paper as [105]

    The Discussion and Results report greater HbA1c and weight reductions with tirzepatide 10 and 15 mg than with semaglutide 2 mg. The claim leaves out that tirzepatide 5 mg showed no significant difference and that this comparison was an adjusted indirect analysis of RCT results, not a head-to-head RCT. (LLM, conf=0.86)

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Research works printed but not linked: 10

  1. [1]Rosenstock J, Wysham C, Frias JP, et al. Efficacy and safety of a novel dual GIP and GLP‐1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS‐1): a double‐blind, randomised, phase 3 trial. Lancet. 2021; 398(10295): 143‐ 155. 34186022
  2. [3]Ludvik B, Giorgino F, Jodar E, et al. Once‐weekly tirzepatide versus once‐daily insulin degludec as add‐on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS‐3): a randomised, open‐label, parallel‐group, phase 3 trial. Lancet. 2021; 398(10300): 583‐ 598. 34370970
  3. [4]Del Prato S, Kahn SE, Pavo I, et al. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS‐4): a randomised, open‐label, parallel‐group, multicentre, phase 3 trial. Lancet. 2021; 398(10313): 1811‐ 1824. 34672967
  4. [8]Ahmann AJ, Capehorn M, Charpentier G, et al. Efficacy and safety of once‐weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): a 56‐week, open‐label, randomized clinical trial. Diabetes Care. 2018; 41(2): 258‐ 266. 29246950
  5. [9]Pratley RE, Aroda VR, Lingvay I, et al. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open‐label, phase 3b trial. Lancet Diabetes Endocrinol. 2018; 6(4): 275‐ 286. 29397376
  6. [11]Bucher HC, Guyatt GH, Griffith LE, Walter SD. The results of direct and indirect treatment comparisons in meta‐analysis of randomized controlled trials. J Clin Epidemiol. 1997; 50(6): 683‐ 691. 9250266
  7. [12]Pratley RE, Catarig AM, Lingvay I, et al. An indirect treatment comparison of the efficacy of semaglutide 1.0 mg versus dulaglutide 3.0 and 4.5 mg. Diabetes Obes Metab. 2021; 23(11): 2513‐ 2520. 34286894 PMC9291551
  8. [13]Evans M, Billings LK, Hakan‐Bloch J, et al. An indirect treatment comparison of the efficacy of insulin degludec/liraglutide (IDegLira) and insulin glargine/lixisenatide (iGlarLixi) in patients with type 2 diabetes uncontrolled on basal insulin. J Med Econ. 2018; 21(4): 340‐ 347. 29164973
  9. [14]Lingvay I, Bauer R, Baker‐Knight J, Lawson J, Pratley R. An indirect treatment comparison of semaglutide 2.0 mg versus dulaglutide 3.0 mg and 4.5 mg using multilevel network meta‐regression. J Clin Endocrinol Metab. 2022; 107(5): 1461‐ 1469. 34922383 PMC9016460
  10. [15]Martin AA, Parks D. An indirect comparison of HbA1c treatment effect with albiglutide and exenatide 2.0 mg QW using the Bucher method. Diabetes Metab Syndr Obes. 2016; 9: 163‐ 168. 27274297 PMC4876841

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Authors
Vadher, K., Patel, H., Mody, R., Levine, J. A., Hoog, M., Cheng, A. Y., Pantalone, K. M., & Sapin, H.
Affiliations
  • Eli Lilly (United Kingdom) (GB)
  • Eli Lilly (United States) (US)
  • University of Toronto (CA)
  • Cleveland Clinic (US)
  • Lilly France SAS Neuilly‐sur‐Seine France
Corresponding author
Vadher, Karan
ORCID
Venue
Diabetes, Obesity and Metabolism
Publisher
Wiley
Published
2022-06-13
Volume
24
Issue
9
Pages
1861-1868
ISSN
  • 1462-8902 (ISSN-L)
  • 1463-1326
DOI
10.1111/dom.14775
PMC
PMC9546430
OpenAlex
W4280488682
Cited by
56
References
3
Citations by year
2026: 6 · 2025: 9 · 2024: 17 · 2023: 19 · 2022: 5
FWCI
9.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes Obesity and Metabolism (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Eli Lilly and Company (N/A)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
Keywords
tirzepatide, semaglutide, type 2 diabetes, glycemic control, HbA1c, weight loss, indirect treatment comparison, metformin, comparative effectiveness, GLP-1 receptor agonists, GIP receptor agonist, dose comparison
MeSH terms
Tirzepatide, Semaglutide, Body Weight, Diabetes Mellitus, Type 2, Double-Blind Method, Glucagon-Like Peptides, Gastric Inhibitory Polypeptide, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Metformin, Treatment Outcome

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