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Study · Systematic review · 2025

17 results

Effectiveness of GLP-1 RAs and SGLT2 inhibitors in preventing T2DM in high-risk patients: an updated systematic review and meta-analysis.

Tsironikos GI, Tsolaki V, Zakynthinos GE, Kyprianidou D, Rammou V, Antonogiannis T, Mprotsis T, Zakynthinos E, Bargiota A

Frontiers in clinical diabetes and healthcare10 Dec 2025Cited by 2 (Europe PMC)

PMID41451292 (opens in a new tab)PMCIDPMC12727544 (opens in a new tab)DOI10.3389/fcdhc.2025.1694808 (opens in a new tab)PepBankPUB-41451292
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Summary

IntroductionThere are conflicting results and limited data regarding the individual effectiveness of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors and their combined action in preventing type 2 diabetes mellitus (T2DM) in high-risk adults. An updated investigation is warranted. We aimed to explore their effectiveness in preventing T2DM in high-risk patients and assess changes in body weight/body mass index (BMI), glycemic parameters, and safety.Materials and methodsPubMed, Cochrane Library Central Register of Controlled Trials, and Scopus were searched for eligible randomized controlled trials (RCTs), and a systematic review (SR) and meta-analysis (MA) were conducted. GRADE assessment was conducted for rating the overall certainty of evidence.ResultsAll 24,157 participants in 10 GLP-1 RA RCTs were overweight/obese. Compared to placebo, GLP-1 RAs reduced T2DM incidence (OR 0.51; 95% CI 0.28, 0.94; P-value 0.03), and 2.4 mg of semaglutide was overall effective (OR 0.38; 95% CI 0.16, 0.94; P-value < 0.0001). Subgroup analysis indicated effectiveness in patients more than 50 years across the world, in cardiovascular disease, after 100 weeks, and during the post-intervention period. Liraglutide was not overall effective. However, subgroup analyses demonstrated effectiveness for studies that were performed worldwide, for women more than 40 years, at 3.0 mg daily, after 55 weeks of administration, and only during intervention. Exenatide was not effective. Heterogeneity was large (Q 54.56, P-value I² 84%, 95% CI 74%, 89%), and MA was performed using the random-effects model. Heterogeneity was explained by countries' performance in semaglutide- and liraglutide-based RCTs and participants' mean age, dosage, duration, and post-intervention evaluation in liraglutide-based RCTs. Sensitivity analyses considering studies with post-intervention assessment and studies with the largest sample size and dropout rate more than 5% in semaglutide-based RCTs explain further heterogeneity. The quality of evidence was low. Compared to placebo, GLP-1 RAs reduced weight (kg) and BMI (kg/m²) (mean difference -6.35, P-value P-value < 0.00001, respectively). Finally, GLP-1 RAs were safe (OR for adverse events 1.01; P-value 0.95).ConclusionsGLP-1 RAs may prevent diabetes in high-risk adults and ameliorate body and glycemic factors. Their effectiveness should be considered carefully due to the low quality of evidence. No safety issues were identified. Future investigation is necessary to provide consistency of estimations.Systematic review registrationOSF Registration, identifier DOI 10.17605/OSF.IO/8XH4.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study17

7 results from studies that gave the peptide. 7 results from people.

  1. 01HumanSystematic reviewEfficacy outcome

    In high-risk adults, semaglutide 2.4 mg was overall effective in reducing type 2 diabetes incidence versus placebo.

    In plain wordsIn adults at high risk, semaglutide 2.4 mg lowered the chance of type 2 diabetes compared with placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseIncidence of type 2 diabetes with semaglutide 2.4 mg
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Cardiometabolic risk factors · Metabolic and weight
    Studied dose
    2.4 mgAs given in this study (human).

    Measurements

    odds ratio
    0.38 OR
    semaglutide 2.4 mg

    Source sentences

    Summary
    2.4 mg of semaglutide was overall effective (OR 0.38; 95% CI 0.16, 0.94; P-value < 0.0001).
    1 context sentence
    Summary · context
    All 24,157 participants in 10 GLP-1 RA RCTs were overweight/obese.
  2. 02HumanSystematic reviewEfficacy outcome

    In high-risk adults, liraglutide was not overall effective in reducing type 2 diabetes incidence.

    In plain wordsIn adults at high risk, liraglutide did not clearly lower the chance of type 2 diabetes overall.

    Peptide
    Liraglutide
    Outcome
    No significant changeOverall effect of liraglutide on type 2 diabetes incidence
    Study

    n: not reported in source

    Outcome group
    Cardiometabolic risk factors · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Liraglutide was not overall effective.
    1 context sentence
    Summary · context
    All 24,157 participants in 10 GLP-1 RA RCTs were overweight/obese.
  3. 03HumanSystematic reviewEfficacy outcome

    In subgroup analyses, liraglutide was effective in studies performed worldwide.

    In plain wordsIn one subgroup of studies run worldwide, liraglutide lowered the chance of type 2 diabetes.

    Peptide
    Liraglutide
    Outcome
    DecreaseLiraglutide subgroup: studies performed worldwide
    Study

    n: not reported in source

    Outcome group
    Cardiometabolic risk factors · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    However, subgroup analyses demonstrated effectiveness for studies that were performed worldwide, for women more than 40 years, at 3.0 mg daily, after 55 weeks of administration, and only during intervention.
    1 context sentence
    Summary · context
    All 24,157 participants in 10 GLP-1 RA RCTs were overweight/obese.
  4. 04HumanSystematic reviewEfficacy outcome

    In subgroup analyses, liraglutide was effective in women more than 40 years old.

    In plain wordsIn one subgroup of women older than 40, liraglutide lowered the chance of type 2 diabetes.

    Peptide
    Liraglutide
    Outcome
    DecreaseLiraglutide subgroup: women older than 40 years
    Study

    n: not reported in source

    Outcome group
    Cardiometabolic risk factors · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    However, subgroup analyses demonstrated effectiveness for studies that were performed worldwide, for women more than 40 years, at 3.0 mg daily, after 55 weeks of administration, and only during intervention.
    1 context sentence
    Summary · context
    All 24,157 participants in 10 GLP-1 RA RCTs were overweight/obese.
  5. 05HumanSystematic reviewEfficacy outcome

    In subgroup analyses, liraglutide at 3.0 mg daily was effective.

    In plain wordsIn one subgroup of studies, liraglutide at 3.0 mg daily lowered the chance of type 2 diabetes.

    Peptide
    Liraglutide
    Outcome
    DecreaseLiraglutide subgroup: 3.0 mg daily
    Study

    n: not reported in source

    Outcome group
    Cardiometabolic risk factors · Metabolic and weight
    Studied dose
    3.0 mg dailyAs given in this study (human).

    Source sentences

    Summary
    However, subgroup analyses demonstrated effectiveness for studies that were performed worldwide, for women more than 40 years, at 3.0 mg daily, after 55 weeks of administration, and only during intervention.
    1 context sentence
    Summary · context
    All 24,157 participants in 10 GLP-1 RA RCTs were overweight/obese.
  6. 06HumanSystematic reviewEfficacy outcome

    In subgroup analyses, liraglutide was effective after 55 weeks of administration.

    In plain wordsIn one subgroup of studies, liraglutide lowered the chance of type 2 diabetes after 55 weeks of use.

    Peptide
    Liraglutide
    Outcome
    DecreaseLiraglutide subgroup: after 55 weeks
    Study

    n: not reported in source

    Outcome group
    Cardiometabolic risk factors · Metabolic and weight
    Studied dose
    Dose not stated · more than 55 weeksAs given in this study (human).

    Source sentences

    Summary
    However, subgroup analyses demonstrated effectiveness for studies that were performed worldwide, for women more than 40 years, at 3.0 mg daily, after 55 weeks of administration, and only during intervention.
    1 context sentence
    Summary · context
    All 24,157 participants in 10 GLP-1 RA RCTs were overweight/obese.
  7. 07HumanSystematic reviewEfficacy outcome

    In subgroup analyses, liraglutide was effective only during the intervention period.

    In plain wordsIn one subgroup of studies, liraglutide lowered the chance of type 2 diabetes only while people were taking it.

    Peptide
    Liraglutide
    Outcome
    DecreaseLiraglutide subgroup: only during intervention
    Study

    n: not reported in source

    Outcome group
    Cardiometabolic risk factors · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    However, subgroup analyses demonstrated effectiveness for studies that were performed worldwide, for women more than 40 years, at 3.0 mg daily, after 55 weeks of administration, and only during intervention.
    1 context sentence
    Summary · context
    All 24,157 participants in 10 GLP-1 RA RCTs were overweight/obese.

Studies that did not test the peptide alone10

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.

  1. 08HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome

    In high-risk adults, pooled GLP-1 RAs (including liraglutide) reduced type 2 diabetes incidence versus placebo.

    In plain wordsIn adults at high risk, GLP-1 drugs as a group lowered the chance of type 2 diabetes compared with placebo.

    Peptide
    Liraglutide
    Outcome
    DecreaseIncidence of type 2 diabetes
    Study

    n = 24,157

    Comparator
    Placebo
    Outcome group
    Cardiometabolic risk factors · Metabolic and weight

    Measurements

    odds ratio
    0.51 OR
    T2DM incidence, GLP-1 RAs vs placebo

    Source sentences

    Summary
    Compared to placebo, GLP-1 RAs reduced T2DM incidence (OR 0.51; 95% CI 0.28, 0.94
    1 context sentence
    Summary · context
    All 24,157 participants in 10 GLP-1 RA RCTs were overweight/obese.

    In this study, Liraglutide 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 Liraglutide.

  2. 09HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome

    In high-risk adults, pooled GLP-1 RAs (including semaglutide) reduced type 2 diabetes incidence versus placebo.

    In plain wordsIn adults at high risk, GLP-1 drugs as a group lowered the chance of type 2 diabetes compared with placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseIncidence of type 2 diabetes
    Study

    n = 24,157

    Comparator
    Placebo
    Outcome group
    Cardiometabolic risk factors · Metabolic and weight

    Measurements

    odds ratio
    0.51 OR
    T2DM incidence, GLP-1 RAs vs placebo

    Source sentences

    Summary
    Compared to placebo, GLP-1 RAs reduced T2DM incidence (OR 0.51; 95% CI 0.28, 0.94
    1 context sentence
    Summary · context
    All 24,157 participants in 10 GLP-1 RA RCTs were overweight/obese.

    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.

  3. 10HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome

    In high-risk adults, subgroup analyses showed effectiveness in people older than 50 years, in cardiovascular disease, after 100 weeks and in the post-intervention period; the abstract does not name the drug.

    In plain wordsIn adults at high risk, GLP-1 drug trials showed a benefit in some subgroups, such as people older than 50. The drug is not named.

    Peptide
    Liraglutide
    Outcome
    DecreaseType 2 diabetes prevention in subgroups of GLP-1 RA trials
    Study

    n: not reported in source

    Outcome group
    Cardiometabolic risk factors · Metabolic and weight

    Source sentences

    Summary
    Subgroup analysis indicated effectiveness in patients more than 50 years across the world, in cardiovascular disease, after 100 weeks, and during the post-intervention period.
    1 context sentence
    Summary · context
    All 24,157 participants in 10 GLP-1 RA RCTs were overweight/obese.

    In this study, Liraglutide 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 Liraglutide.

  4. 11HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome

    In high-risk adults, subgroup analyses showed effectiveness in people older than 50 years, in cardiovascular disease, after 100 weeks and in the post-intervention period; the abstract does not name the drug.

    In plain wordsIn adults at high risk, GLP-1 drug trials showed a benefit in some subgroups, such as people older than 50. The drug is not named.

    Peptide
    Semaglutide
    Outcome
    DecreaseType 2 diabetes prevention in subgroups of GLP-1 RA trials
    Study

    n: not reported in source

    Outcome group
    Cardiometabolic risk factors · Metabolic and weight

    Source sentences

    Summary
    Subgroup analysis indicated effectiveness in patients more than 50 years across the world, in cardiovascular disease, after 100 weeks, and during the post-intervention period.
    1 context sentence
    Summary · context
    All 24,157 participants in 10 GLP-1 RA RCTs were overweight/obese.

    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.

  5. 12HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome

    In high-risk adults, pooled GLP-1 RAs (including liraglutide) reduced body weight versus placebo.

    In plain wordsIn adults at high risk, GLP-1 drugs as a group lowered body weight more than placebo.

    Peptide
    Liraglutide
    Outcome
    DecreaseBody weight change
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Body weight · Metabolic and weight

    Measurements

    mean difference
    −6.35 kg
    GLP-1 RAs vs placebo

    Source sentences

    Summary
    Compared to placebo, GLP-1 RAs reduced weight (kg) and BMI (kg/m²) (mean difference -6.35, P-value P-value < 0.00001, respectively).
    1 context sentence
    Summary · context
    All 24,157 participants in 10 GLP-1 RA RCTs were overweight/obese.

    In this study, Liraglutide 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 Liraglutide.

  6. 13HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome

    In high-risk adults, pooled GLP-1 RAs (including semaglutide) reduced body weight versus placebo.

    In plain wordsIn adults at high risk, GLP-1 drugs as a group lowered body weight more than placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseBody weight change
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Body weight · Metabolic and weight

    Measurements

    mean difference
    −6.35 kg
    GLP-1 RAs vs placebo

    Source sentences

    Summary
    Compared to placebo, GLP-1 RAs reduced weight (kg) and BMI (kg/m²) (mean difference -6.35, P-value P-value < 0.00001, respectively).
    1 context sentence
    Summary · context
    All 24,157 participants in 10 GLP-1 RA RCTs were overweight/obese.

    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.

  7. 14HumanNot a test of Liraglutide aloneSystematic reviewEfficacy outcome

    In high-risk adults, pooled GLP-1 RAs (including liraglutide) reduced BMI versus placebo.

    In plain wordsIn adults at high risk, GLP-1 drugs as a group lowered BMI more than placebo.

    Peptide
    Liraglutide
    Outcome
    DecreaseBMI change
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Body weight · Metabolic and weight

    Measurements

    mean difference
    −2.46 kg/m²
    GLP-1 RAs vs placebo

    Source sentences

    Summary
    Compared to placebo, GLP-1 RAs reduced weight (kg) and BMI (kg/m²) (mean difference -6.35, P-value P-value < 0.00001, respectively).
    1 context sentence
    Summary · context
    All 24,157 participants in 10 GLP-1 RA RCTs were overweight/obese.

    In this study, Liraglutide 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 Liraglutide.

  8. 15HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome

    In high-risk adults, pooled GLP-1 RAs (including semaglutide) reduced BMI versus placebo.

    In plain wordsIn adults at high risk, GLP-1 drugs as a group lowered BMI more than placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseBMI change
    Study

    n: not reported in source

    Comparator
    Placebo
    Outcome group
    Body weight · Metabolic and weight

    Measurements

    mean difference
    −2.46 kg/m²
    GLP-1 RAs vs placebo

    Source sentences

    Summary
    Compared to placebo, GLP-1 RAs reduced weight (kg) and BMI (kg/m²) (mean difference -6.35, P-value P-value < 0.00001, respectively).
    1 context sentence
    Summary · context
    All 24,157 participants in 10 GLP-1 RA RCTs were overweight/obese.

    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.

  9. 16HumanNot a test of Liraglutide aloneSystematic reviewSafety outcome

    In high-risk adults, pooled GLP-1 RAs (including liraglutide) were safe, with an odds ratio for adverse events of 1.01.

    In plain wordsIn adults at high risk, GLP-1 drugs as a group did not raise adverse events in this review.

    Peptide
    Liraglutide
    Outcome
    No significant changeAdverse events
    Study

    n: not reported in source

    Outcome group
    Adverse events · Whole body

    Measurements

    odds ratio
    1.01 OR
    adverse events

    Source sentences

    Summary
    Finally, GLP-1 RAs were safe (OR for adverse events 1.01; P-value 0.95).
    1 context sentence
    Summary · context
    All 24,157 participants in 10 GLP-1 RA RCTs were overweight/obese.

    In this study, Liraglutide 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 Liraglutide.

  10. 17HumanNot a test of Semaglutide aloneSystematic reviewSafety outcome

    In high-risk adults, pooled GLP-1 RAs (including semaglutide) were safe, with an odds ratio for adverse events of 1.01.

    In plain wordsIn adults at high risk, GLP-1 drugs as a group did not raise adverse events in this review.

    Peptide
    Semaglutide
    Outcome
    No significant changeAdverse events
    Study

    n: not reported in source

    Outcome group
    Adverse events · Whole body

    Measurements

    odds ratio
    1.01 OR
    adverse events

    Source sentences

    Summary
    Finally, GLP-1 RAs were safe (OR for adverse events 1.01; P-value 0.95).
    1 context sentence
    Summary · context
    All 24,157 participants in 10 GLP-1 RA RCTs were overweight/obese.

    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.

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.

  1. Version 3Current

    12 Oct 2026, 11:11 UTC

    Study results updated

  2. Version 2

    9 Oct 2026, 03:06 UTC

    Study data updated · source update from Europe PMC

  3. Version 1

    9 Oct 2026, 03:05 UTC

    First added · source update from Europe PMC

Subjects

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