Basal insulin intensification with GLP-1RA and dual GIP and GLP-1RA in patients with uncontrolled type 2 diabetes mellitus: A rapid review of randomized controlled trials and meta-analysis.

Lisco G, De Tullio A, Disoteo O, De Geronimo V, Piazzolla G, De Pergola G, Giagulli VA, Jirillo E, Guastamacchia E, Sabbà C, Triggiani V

Frontiers in endocrinology8 Sept 2022Cited by 16 (Europe PMC)

PMID36157450PMCIDPMC9494570DOI10.3389/fendo.2022.920541PepBankPUB-36157450

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Summary

Tirzepatide, a dual agonist of Glucose-Dependent Insulinotropic Polypeptide (GIP) and Glucagon-Like Peptide 1 (GLP-1) receptors, improved glucose control and reduced body weight in different therapeutic approaches. Herein, we overviewed the role of GIP and GLP-1 in the pathophysiology of type 2 diabetes and systematically reviewed the efficacy and safety of injectable incretin-based therapy added to basal insulin in light of the results of the SURPASS-5 trial. We identified eleven randomized clinical trials. GLP-1 receptor agonists (GLP-1RAs) or Tirzepatide added to basal insulin than rigorously titrated basal insulin significantly ameliorates glucose control (Δ HbA_1c = -1%, 95% CI -1.25; -0.74, I² 94%; Δ FPG = -14.6 mg/dL, 95% CI -21.6-; -7.6, I² 90%; chance to achieve HbA_{1c <}7% = RR 2.62, 95% CI 2.10; 3.26, I² 89%), reduces body weight (Δ = -3.95 kg, 95% CI -5.1, -2.79, I² 96%) without increasing the risk of hypoglycemia (RR = 1.01, 95% CI 0.86; 1.18, I² 7.7%). Tirzepatide provides an impressive weight loss exceeding that observed with GLP-1RAs. Injectable incretin-based therapy plus basal insulin remains a potent and safe therapeutic approach in uncontrolled type 2 diabetes patients previously treated with basal insulin alone. Tirzepatide is expected to ameliorate the management of "diabesity" in this usually difficult-to-treat cluster of patients.

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

Results from this study5

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone5

In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Tirzepatide.

01HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes, pooled GLP-1 receptor agonists or tirzepatide added to basal insulin reduced HbA1c more than titrated basal insulin.
In plain wordsIn adults with type 2 diabetes, adding a GLP-1 drug or tirzepatide to basal insulin lowered HbA1c more than insulin alone.
Peptide
Tirzepatide
Outcome
DecreaseHbA1c change
Study
n: not reported in source
Comparator
Titrated basal insulin
Outcome group
Glycemic control · Metabolic and weight
Measurements
Delta HbA1c
−1%
pooled GLP-1RA or tirzepatide plus basal insulin
Source sentences
Summary
GLP-1 receptor agonists (GLP-1RAs) or Tirzepatide added to basal insulin than rigorously titrated basal insulin significantly ameliorates glucose control (Δ HbA_1c = -1%, 95% CI -1.25; -0.74, I² 94%
1 context sentence(design, population, supporting numbers)
Summary · context
We identified eleven randomized clinical trials.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-3615745001
02HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes, pooled GLP-1 receptor agonists or tirzepatide added to basal insulin reduced fasting plasma glucose more than titrated basal insulin.
In plain wordsIn adults with type 2 diabetes, adding a GLP-1 drug or tirzepatide to basal insulin lowered fasting glucose more than insulin alone.
Peptide
Tirzepatide
Outcome
DecreaseFasting plasma glucose change
Study
n: not reported in source
Comparator
Titrated basal insulin
Outcome group
Glycemic control · Metabolic and weight
Measurements
Delta FPG
−14.6 mg/dL
pooled GLP-1RA or tirzepatide plus basal insulin
Source sentences
Summary
Δ FPG = -14.6 mg/dL, 95% CI -21.6-; -7.6, I² 90%
1 context sentence(design, population, supporting numbers)
Summary · context
We identified eleven randomized clinical trials.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-3615745002
03HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes, pooled GLP-1 receptor agonists or tirzepatide added to basal insulin raised the chance of reaching HbA1c below 7% compared with titrated basal insulin.
In plain wordsIn adults with type 2 diabetes, adding a GLP-1 drug or tirzepatide to basal insulin made reaching HbA1c below 7% more likely than insulin alone.
Peptide
Tirzepatide
Outcome
IncreaseChance of reaching HbA1c below 7%
Study
n: not reported in source
Comparator
Titrated basal insulin
Outcome group
Glycemic control · Metabolic and weight
Measurements
RR
2.62 ratio
HbA1c <7%
Source sentences
Summary
chance to achieve HbA_{1c <}7% = RR 2.62, 95% CI 2.10; 3.26, I² 89%
1 context sentence(design, population, supporting numbers)
Summary · context
We identified eleven randomized clinical trials.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-3615745003
04HumanNot a test of Tirzepatide aloneSystematic reviewEfficacy outcome
In adults with type 2 diabetes, pooled GLP-1 receptor agonists or tirzepatide added to basal insulin reduced body weight compared with titrated basal insulin.
In plain wordsIn adults with type 2 diabetes, adding a GLP-1 drug or tirzepatide to basal insulin reduced body weight compared with insulin alone.
Peptide
Tirzepatide
Outcome
DecreaseBody weight change
Study
n: not reported in source
Comparator
Titrated basal insulin
Outcome group
Body weight · Metabolic and weight
Measurements
Delta body weight
−3.95 kg
pooled GLP-1RA or tirzepatide plus basal insulin
Source sentences
Summary
reduces body weight (Δ = -3.95 kg, 95% CI -5.1, -2.79, I² 96%)
1 context sentence(design, population, supporting numbers)
Summary · context
We identified eleven randomized clinical trials.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-3615745004
05HumanNot a test of Tirzepatide aloneSystematic reviewSafety outcome
In adults with type 2 diabetes, pooled GLP-1 receptor agonists or tirzepatide added to basal insulin did not increase the risk of hypoglycemia compared with titrated basal insulin.
In plain wordsIn adults with type 2 diabetes, adding a GLP-1 drug or tirzepatide to basal insulin did not raise low blood sugar risk versus insulin alone.
Peptide
Tirzepatide
Outcome
No significant changeHypoglycemia risk
Study
n: not reported in source
Comparator
Titrated basal insulin
Outcome group
Adverse events · Metabolic and weight
Measurements
RR
1.01 ratio
hypoglycemia
Source sentences
Summary
without increasing the risk of hypoglycemia (RR = 1.01, 95% CI 0.86; 1.18, I² 7.7%).
1 context sentence(design, population, supporting numbers)
Summary · context
We identified eleven randomized clinical trials.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-3615745005

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, 12:58 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC

Subjects

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