Effects of tirzepatide versus insulin glargine on kidney outcomes in type 2 diabetes in the SURPASS-4 trial: post-hoc analysis of an open-label, randomised, phase 3 trial.

Heerspink HJL, Sattar N, Pavo I, Haupt A, Duffin KL, Yang Z, Wiese RJ, Tuttle KR, Cherney DZI

The lancet. Diabetes & endocrinology21 Sept 2022Cited by 233 (Europe PMC)

PMID36152639DOI10.1016/s2213-8587(22)00243-1PepBankPUB-36152639

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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study4

4 results from studies that gave the peptide. 4 results from people.

01HumanRandomized controlled trialEfficacy outcome
In a post-hoc SURPASS-4 analysis of adults with type 2 diabetes and high cardiovascular risk, the annual eGFR decline was slower with combined tirzepatide groups than with insulin glargine (-1·4 vs -3·6 mL/min per 1·73 m² per year; between-group difference 2·2, 95% CI 1·6 to 2·8).
In plain wordsIn adults with type 2 diabetes at high heart risk, kidney function (eGFR) fell more slowly with tirzepatide than with insulin glargine.
Peptide
Tirzepatide
Outcome
DecreaseAnnual rate of eGFR decline
Study
n = 2,002
Comparator
Titrated once-daily insulin glargine (100 U/mL), subcutaneous
Outcome group
Kidney function · Kidney and urinary
Studied dose
5 mg, 10 mg or 15 mg once weekly · subcutaneous · up to 104 weeks (median 85 weeks)As given in this study (human).
Source sentences
Summary
The mean rate of eGFR decline was -1·4 (SE 0·2) mL/min per 1·73 m² per year in the combined tirzepatide groups and -3·6 (0·2) mL/min per 1·73 m² per year in the insulin group (between-group difference 2·2 [95% CI 1·6 to 2·8]).
2 context sentences(design, population, supporting numbers)
Summary · context
We did a post-hoc analysis of data from SURPASS-4, a randomised, open-label, parallel-group, phase 3 study at 187 sites
Summary · context
Randomisation via an interactive web-response system was 1:1:1:3 to a once-weekly subcutaneous injection of tirzepatide (5 mg, 10 mg, or 15 mg) or a once-daily subcutaneous injection of titrated insulin glargine (100 U/mL)
Report a problemFND-3615263901
02HumanRandomized controlled trialEfficacy outcome
In the post-hoc SURPASS-4 analysis, UACR rose from baseline with insulin glargine (36·9%) but not with tirzepatide (-6·8%), a between-group difference of -31·9% (95% CI -37·7 to -25·7).
In plain wordsIn adults with type 2 diabetes, a urine marker of kidney damage (UACR) rose with insulin glargine but not with tirzepatide.
Peptide
Tirzepatide
Outcome
DecreaseUrine albumin-creatinine ratio (UACR) change from baseline
Study
n = 2,002
Comparator
Titrated once-daily insulin glargine (100 U/mL), subcutaneous
Outcome group
Kidney function · Kidney and urinary
Studied dose
5 mg, 10 mg or 15 mg once weekly · subcutaneous · up to 104 weeks (median 85 weeks)As given in this study (human).
Source sentences
Summary
UACR increased from baseline to follow-up with insulin glargine (36·9% [95% CI 26·0 to 48·7]) but not with tirzepatide (-6·8% [-14·1 to 1·1]; between-group difference -31·9% [-37·7 to -25·7]).
2 context sentences(design, population, supporting numbers)
Summary · context
We did a post-hoc analysis of data from SURPASS-4, a randomised, open-label, parallel-group, phase 3 study at 187 sites
Summary · context
Randomisation via an interactive web-response system was 1:1:1:3 to a once-weekly subcutaneous injection of tirzepatide (5 mg, 10 mg, or 15 mg) or a once-daily subcutaneous injection of titrated insulin glargine (100 U/mL)
Report a problemFND-3615263903
03HumanRandomized controlled trialEfficacy outcome
In the post-hoc SURPASS-4 analysis, tirzepatide significantly lowered the occurrence of the composite kidney endpoint compared with insulin glargine (hazard ratio 0·58, 95% CI 0·43 to 0·80).
In plain wordsIn adults with type 2 diabetes at high heart risk, a combined measure of kidney problems occurred less often with tirzepatide than with insulin glargine.
Peptide
Tirzepatide
Outcome
DecreaseComposite kidney outcome
Study
n = 2,002
Comparator
Titrated once-daily insulin glargine (100 U/mL), subcutaneous
Outcome group
Kidney function · Kidney and urinary
Studied dose
5 mg, 10 mg or 15 mg once weekly · subcutaneous · up to 104 weeks (median 85 weeks)As given in this study (human).
Source sentences
Summary
Participants who received tirzepatide showed a significantly lower occurrence of the composite kidney endpoint compared with those who received insulin glargine (hazard ratio 0·58 [95% CI 0·43 to 0·80]).
3 context sentences(design, population, supporting numbers)
Summary · context
The kidney composite outcome was time to first occurrence of eGFR decline of at least 40% from baseline, end-stage kidney disease, death owing to kidney failure, or new-onset macroalbuminuria.
Summary · context
We did a post-hoc analysis of data from SURPASS-4, a randomised, open-label, parallel-group, phase 3 study at 187 sites
Summary · context
Randomisation via an interactive web-response system was 1:1:1:3 to a once-weekly subcutaneous injection of tirzepatide (5 mg, 10 mg, or 15 mg) or a once-daily subcutaneous injection of titrated insulin glargine (100 U/mL)
Report a problemFND-3615263904
04HumanRandomized controlled trialEfficacy outcome
In the post-hoc SURPASS-4 analysis, the reduction in annual eGFR decline with tirzepatide versus insulin glargine was larger in participants with eGFR below 60 mL/min per 1·73 m² than in those with eGFR 60 or higher (between-group difference 3·7, 95% CI 2·4 to 5·1).
In plain wordsIn type 2 diabetes, tirzepatide slowed kidney function decline more than insulin glargine, and the gap was larger when starting kidney function was lower.
Peptide
Tirzepatide
Outcome
DecreaseAnnual rate of eGFR decline in participants with eGFR below 60
Study
n: not reported in source
Comparator
Titrated once-daily insulin glargine (100 U/mL), subcutaneous
Outcome group
Kidney function · Kidney and urinary
Studied dose
5 mg, 10 mg or 15 mg once weekly · subcutaneous · up to 104 weeks (median 85 weeks)As given in this study (human).
Source sentences
Summary
Compared with insulin glargine, the reduction in the annual rate of eGFR decline induced by tirzepatide was more pronounced in participants with eGFR less than 60 mL/min per 1·73 m² than in those with eGFR 60 mL/min per 1·73 m² or higher (between-group difference 3·7 [95% CI 2·4 to 5·1]).
2 context sentences(design, population, supporting numbers)
Summary · context
We did a post-hoc analysis of data from SURPASS-4, a randomised, open-label, parallel-group, phase 3 study at 187 sites
Summary · context
Randomisation via an interactive web-response system was 1:1:1:3 to a once-weekly subcutaneous injection of tirzepatide (5 mg, 10 mg, or 15 mg) or a once-daily subcutaneous injection of titrated insulin glargine (100 U/mL)
Report a problemFND-3615263902

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT03730662

A Study of Tirzepatide (LY3298176) Once a Week Versus Insulin Glargine Once a Day in Participants With Type 2 Diabetes and Increased Cardiovascular Risk

Eli Lilly and Companyn = 2,00220 Nov 2018 to 22 Apr 2021

Type 2 Diabetes Mellitus

Trial page ClinicalTrials.govUpdated 14 Feb 2022

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
9 Oct 2026, 12:39 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC

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