Single and Combined Impact of Semaglutide, Tirzepatide, and Metformin on β-Cell Maintenance and Function Under High-Glucose-High-Lipid Conditions: A Comparative Study.

Gojani EG, Wang B, Li D, Kovalchuk O, Kovalchuk I

International journal of molecular sciences6 Jan 2025Cited by 3 (Europe PMC)

PMID39796271PMCIDPMC11720205DOI10.3390/ijms26010421PepBankPUB-39796271

Summary

Type 2 diabetes (T2D), the most common form, is marked by insulin resistance and β-cell failure. β-cell dysfunction under high-glucose-high-lipid (HG-HL) conditions is a key contributor to the progression of T2D. This study evaluates the comparative effects of 10 nM semaglutide, 10 nM tirzepatide, and 1 mM metformin, both alone and in combination, on INS-1 β-cell maintenance and function under HG-HL conditions. INS-1 cells were pretreated for 2 h with single doses of metformin (1 mM), semaglutide (10 nM), tirzepatide (10 nM), or combinations of 1 mM metformin with either 10 nM semaglutide or 10 nM tirzepatide, followed by 48 h of HG-HL stimulation. The results indicate that combining 1 mM metformin with either 10 nM semaglutide or 10 nM tirzepatide significantly enhances the effects of 10 nM semaglutide and 10 nM tirzepatide on HG-HL-induced apoptosis and dysregulated cell cycle. Specifically, the combination treatments demonstrated superior restoration of glucose-stimulated insulin secretion (GSIS) functionality compared to 1 mM metformin, 10 nM semaglutide, and 10 nM tirzepatide.

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

Results from this study6

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

Studies that did not test the peptide alone6

In this study, the peptide 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 the peptide.

01LabNot a test of Semaglutide aloneIn vitro (cells)Efficacy outcome
In INS-1 β-cells under high-glucose-high-lipid conditions, metformin combined with semaglutide significantly enhanced the effects of semaglutide on apoptosis.
In plain wordsIn cells, metformin plus semaglutide worked better than semaglutide alone against cell death caused by high glucose and fat.
Peptide
Semaglutide
Outcome
Direction not reportedHG-HL-induced apoptosis
Study
n: not reported in source
INS-1 β-cells under high-glucose-high-lipid conditions
Comparator
Each single drug alone
Outcome group
Cell viability and death · Endocrine and hormones
Source sentences
Summary
The results indicate that combining 1 mM metformin with either 10 nM semaglutide or 10 nM tirzepatide significantly enhances the effects of 10 nM semaglutide and 10 nM tirzepatide on HG-HL-induced apoptosis and dysregulated cell cycle.
1 context sentence(design, population, supporting numbers)
Summary · context
INS-1 cells were pretreated for 2 h with single doses of metformin (1 mM), semaglutide (10 nM), tirzepatide (10 nM), or combinations of 1 mM metformin with either 10 nM semaglutide or 10 nM tirzepatide, followed by 48 h of HG-HL stimulation.
In this study, Semaglutide 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 Semaglutide.
Show in the study text Report a problemFND-3979627101
02LabNot a test of Semaglutide aloneIn vitro (cells)Efficacy outcome
In INS-1 β-cells under high-glucose-high-lipid conditions, metformin combined with semaglutide significantly enhanced the effects of semaglutide on dysregulated cell cycle.
In plain wordsIn cells, metformin plus semaglutide worked better than semaglutide alone on cell-cycle changes caused by high glucose and fat.
Peptide
Semaglutide
Outcome
Direction not reportedHG-HL-induced dysregulated cell cycle
Study
n: not reported in source
INS-1 β-cells under high-glucose-high-lipid conditions
Comparator
Each single drug alone
Outcome group
Cell viability and death · Endocrine and hormones
Source sentences
Summary
The results indicate that combining 1 mM metformin with either 10 nM semaglutide or 10 nM tirzepatide significantly enhances the effects of 10 nM semaglutide and 10 nM tirzepatide on HG-HL-induced apoptosis and dysregulated cell cycle.
1 context sentence(design, population, supporting numbers)
Summary · context
INS-1 cells were pretreated for 2 h with single doses of metformin (1 mM), semaglutide (10 nM), tirzepatide (10 nM), or combinations of 1 mM metformin with either 10 nM semaglutide or 10 nM tirzepatide, followed by 48 h of HG-HL stimulation.
In this study, Semaglutide 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 Semaglutide.
Show in the study text Report a problemFND-3979627102
03LabNot a test of Semaglutide aloneIn vitro (cells)Efficacy outcome
In INS-1 β-cells under high-glucose-high-lipid conditions, metformin combined with semaglutide restored glucose-stimulated insulin secretion better than metformin, semaglutide or tirzepatide alone.
In plain wordsIn cells, metformin plus semaglutide restored insulin release better than metformin, semaglutide or tirzepatide alone.
Peptide
Semaglutide
Outcome
IncreaseGlucose-stimulated insulin secretion
Study
n: not reported in source
INS-1 β-cells under high-glucose-high-lipid conditions
Comparator
Each single drug alone
Outcome group
Glycemic control · Endocrine and hormones
Source sentences
Summary
Specifically, the combination treatments demonstrated superior restoration of glucose-stimulated insulin secretion (GSIS) functionality compared to 1 mM metformin, 10 nM semaglutide, and 10 nM tirzepatide.
1 context sentence(design, population, supporting numbers)
Summary · context
INS-1 cells were pretreated for 2 h with single doses of metformin (1 mM), semaglutide (10 nM), tirzepatide (10 nM), or combinations of 1 mM metformin with either 10 nM semaglutide or 10 nM tirzepatide, followed by 48 h of HG-HL stimulation.
In this study, Semaglutide 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 Semaglutide.
Show in the study text Report a problemFND-3979627103
04LabNot a test of Tirzepatide aloneIn vitro (cells)Efficacy outcome
In INS-1 β-cells under high-glucose-high-lipid conditions, metformin combined with tirzepatide significantly enhanced the effects of tirzepatide on apoptosis.
In plain wordsIn cells, metformin plus tirzepatide worked better than tirzepatide alone against cell death caused by high glucose and fat.
Peptide
Tirzepatide
Outcome
Direction not reportedHG-HL-induced apoptosis
Study
n: not reported in source
INS-1 β-cells under high-glucose-high-lipid conditions
Comparator
Each single drug alone
Outcome group
Cell viability and death · Endocrine and hormones
Source sentences
Summary
The results indicate that combining 1 mM metformin with either 10 nM semaglutide or 10 nM tirzepatide significantly enhances the effects of 10 nM semaglutide and 10 nM tirzepatide on HG-HL-induced apoptosis and dysregulated cell cycle.
1 context sentence(design, population, supporting numbers)
Summary · context
INS-1 cells were pretreated for 2 h with single doses of metformin (1 mM), semaglutide (10 nM), tirzepatide (10 nM), or combinations of 1 mM metformin with either 10 nM semaglutide or 10 nM tirzepatide, followed by 48 h of HG-HL stimulation.
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-3979627104
05LabNot a test of Tirzepatide aloneIn vitro (cells)Efficacy outcome
In INS-1 β-cells under high-glucose-high-lipid conditions, metformin combined with tirzepatide significantly enhanced the effects of tirzepatide on dysregulated cell cycle.
In plain wordsIn cells, metformin plus tirzepatide worked better than tirzepatide alone on cell-cycle changes caused by high glucose and fat.
Peptide
Tirzepatide
Outcome
Direction not reportedHG-HL-induced dysregulated cell cycle
Study
n: not reported in source
INS-1 β-cells under high-glucose-high-lipid conditions
Comparator
Each single drug alone
Outcome group
Cell viability and death · Endocrine and hormones
Source sentences
Summary
The results indicate that combining 1 mM metformin with either 10 nM semaglutide or 10 nM tirzepatide significantly enhances the effects of 10 nM semaglutide and 10 nM tirzepatide on HG-HL-induced apoptosis and dysregulated cell cycle.
1 context sentence(design, population, supporting numbers)
Summary · context
INS-1 cells were pretreated for 2 h with single doses of metformin (1 mM), semaglutide (10 nM), tirzepatide (10 nM), or combinations of 1 mM metformin with either 10 nM semaglutide or 10 nM tirzepatide, followed by 48 h of HG-HL stimulation.
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-3979627105
06LabNot a test of Tirzepatide aloneIn vitro (cells)Efficacy outcome
In INS-1 β-cells under high-glucose-high-lipid conditions, metformin combined with tirzepatide restored glucose-stimulated insulin secretion better than metformin, semaglutide or tirzepatide alone.
In plain wordsIn cells, metformin plus tirzepatide restored insulin release better than metformin, semaglutide or tirzepatide alone.
Peptide
Tirzepatide
Outcome
IncreaseGlucose-stimulated insulin secretion
Study
n: not reported in source
INS-1 β-cells under high-glucose-high-lipid conditions
Comparator
Each single drug alone
Outcome group
Glycemic control · Endocrine and hormones
Source sentences
Summary
Specifically, the combination treatments demonstrated superior restoration of glucose-stimulated insulin secretion (GSIS) functionality compared to 1 mM metformin, 10 nM semaglutide, and 10 nM tirzepatide.
1 context sentence(design, population, supporting numbers)
Summary · context
INS-1 cells were pretreated for 2 h with single doses of metformin (1 mM), semaglutide (10 nM), tirzepatide (10 nM), or combinations of 1 mM metformin with either 10 nM semaglutide or 10 nM tirzepatide, followed by 48 h of HG-HL stimulation.
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-3979627106

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 3Current
11 Oct 2026, 00:04 UTC
Study results updated
Version 2
9 Oct 2026, 03:07 UTC
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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