Tirzepatide as Adjunct to Insulin in Adults With Type 1 Diabetes and Overweight or Obesity: A Systematic Review of Randomized and Real-World Evidence.

Acucella GA, Caponio D

Endocrinology, diabetes & metabolism1 May 2026

PMID42007544PMCIDPMC13093900DOI10.1002/edm2.70225PepBankPUB-42007544

Summary

BackgroundOverweight and obesity are increasingly common in adults with type 1 diabetes (T1D), contributing to insulin resistance, higher insulin requirements, and greater cardiometabolic burden. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, has shown major metabolic benefits in type 2 diabetes and obesity, but its role in T1D remains unclear. This systematic review evaluated tirzepatide as adjunctive therapy to insulin in adults with T1D and overweight or obesity.MethodsThis review followed PRISMA 2020 and was registered in PROSPERO (CRD420261335230). PubMed/MEDLINE, Embase, Scopus, Web of Science Core Collection, and ClinicalTrials.gov were searched from inception to March 1, 2026. Eligible studies included randomized and observational studies reporting efficacy or safety outcomes of tirzepatide added to insulin in adults with T1D. Because of marked clinical and methodological heterogeneity, findings were synthesized qualitatively without meta-analysis, and certainty of evidence was assessed using a GRADE-based framework.ResultsEight studies were included: one small 12-week phase 2 randomized placebo-controlled trial and seven observational studies, most at serious risk of bias. The most consistent finding was body weight reduction. In the randomized trial, tirzepatide reduced mean body weight by 10.3 kg, with an estimated treatment difference of 8.7 kg versus placebo, corresponding to an 8.8% reduction from baseline. A placebo-adjusted 35.1% reduction in total daily insulin dose and a between-group HbA1c difference of -0.4 percentage points were also reported, although glycaemic findings were short-term and imprecise. Gastrointestinal adverse events were the most frequent safety findings. Evidence certainty was low or very low.ConclusionsTirzepatide may be a promising investigational adjunct in selected adults with T1D and overweight or obesity, particularly for weight reduction. However, current evidence remains insufficient to establish durable glycaemic benefit or long-term safety. Larger randomized trials are needed.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

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

01HumanSystematic reviewEfficacy outcome
In adults with type 1 diabetes and overweight or obesity, tirzepatide added to insulin reduced mean body weight by 10.3 kg, 8.7 kg more than placebo, in the randomised trial.
In plain wordsIn adults with type 1 diabetes and overweight or obesity, tirzepatide added to insulin cut body weight more than placebo in one small trial.
Peptide
Tirzepatide
Outcome
DecreaseBody weight reduction in the randomised trial
Study
n: not reported in source
Comparator
Placebo
Outcome group
Body weight · Metabolic and weight
Studied dose
Dose not stated · 12 weeksAs given in this study (human).
Measurements
body weight reduction
10.3 kg
tirzepatide
treatment difference versus placebo
8.7 kg
tirzepatide
reduction from baseline
8.8%
tirzepatide
Source sentences
Summary
In the randomized trial, tirzepatide reduced mean body weight by 10.3 kg, with an estimated treatment difference of 8.7 kg versus placebo, corresponding to an 8.8% reduction from baseline.
1 context sentence(design, population, supporting numbers)
Summary · context
Eight studies were included: one small 12-week phase 2 randomized placebo-controlled trial and seven observational studies, most at serious risk of bias.
Show in the study text Report a problemFND-4200754401
02HumanSystematic reviewEfficacy outcome
In adults with type 1 diabetes and overweight or obesity, tirzepatide added to insulin gave a placebo-adjusted 35.1% reduction in total daily insulin dose.
In plain wordsIn adults with type 1 diabetes and overweight or obesity, tirzepatide lowered the daily insulin dose by 35.1% more than placebo in one small trial.
Peptide
Tirzepatide
Outcome
DecreaseTotal daily insulin dose
Study
n: not reported in source
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · 12 weeksAs given in this study (human).
Measurements
placebo-adjusted insulin dose reduction
35.1%
tirzepatide
Source sentences
Summary
A placebo-adjusted 35.1% reduction in total daily insulin dose
1 context sentence(design, population, supporting numbers)
Summary · context
Eight studies were included: one small 12-week phase 2 randomized placebo-controlled trial and seven observational studies, most at serious risk of bias.
Show in the study text Report a problemFND-4200754402
03HumanSystematic reviewEfficacy outcome
In adults with type 1 diabetes and overweight or obesity, the between-group HbA1c difference with tirzepatide versus placebo was -0.4 percentage points, short-term and imprecise.
In plain wordsIn adults with type 1 diabetes and overweight or obesity, HbA1c was 0.4 points lower with tirzepatide than placebo, a short-term and imprecise result.
Peptide
Tirzepatide
Outcome
DecreaseHbA1c between-group difference
Study
n: not reported in source
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
Dose not stated · 12 weeksAs given in this study (human).
Measurements
HbA1c difference versus placebo
−0.4 percentage points
tirzepatide
Source sentences
Summary
a between-group HbA1c difference of -0.4 percentage points were also reported, although glycaemic findings were short-term and imprecise.
1 context sentence(design, population, supporting numbers)
Summary · context
Eight studies were included: one small 12-week phase 2 randomized placebo-controlled trial and seven observational studies, most at serious risk of bias.
Show in the study text Report a problemFND-4200754403
04HumanSystematic reviewSafety outcome
In adults with type 1 diabetes and overweight or obesity, gastrointestinal adverse events were the most frequent safety findings with tirzepatide added to insulin.
In plain wordsIn adults with type 1 diabetes and overweight or obesity, stomach and gut side effects were the most common safety problem with tirzepatide.
Peptide
Tirzepatide
Outcome
Not applicableGastrointestinal adverse events
Study
n: not reported in source
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
Dose not stated
Source sentences
Summary
Gastrointestinal adverse events were the most frequent safety findings.
1 context sentence(design, population, supporting numbers)
Summary · context
Eight studies were included: one small 12-week phase 2 randomized placebo-controlled trial and seven observational studies, most at serious risk of bias.
Show in the study text Report a problemFND-4200754404

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

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
12 Oct 2026, 12:10 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC

Subjects

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