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Published on: February 28, 2013
Factors that may Account for Cardiovascular Risk Reduction with a Dipeptidyl Peptidase-4 Inhibitor, Vildagliptin, in
Marc Evans1, Plamen Kozlovski2, Päivi M Paldánius2
1Diabetes Resource Centre, University Hospital Llandough, Cardiff, UK. marclyndon1@hotmail.com.
Insights
Vildagliptin reduced major adverse cardiac events in younger patients with type 2 diabetes mellitus (T2DM). This benefit in patients under 65 may be linked to improvements in systolic blood pressure, LDL cholesterol, weight, and fewer hypoglycemic events.
Area of Science:
- Cardiovascular Medicine
- Endocrinology
- Pharmacology
Background:
- A meta-analysis revealed vildagliptin significantly reduced major adverse cardiac events (MACE) by 37% in patients under 65 with type 2 diabetes mellitus (T2DM).
- The risk reduction was not observed in patients aged 65 and older.
- An exploratory analysis was conducted to understand factors influencing these age-related outcome differences.
Purpose of the Study:
- To identify patient characteristics and on-treatment effects contributing to differential MACE outcomes with vildagliptin in younger versus older T2DM patients.
- To explore potential mechanisms behind the observed age-specific cardiovascular benefits of vildagliptin.
Main Methods:
- Analysis of covariance (ANCOVA) was used to assess on-treatment differences in cardiovascular risk factors (HbA1c, lipids, blood pressure, weight) between vildagliptin and comparator groups.
- Adjustments were made for baseline values, treatment, study, and background antihypertensive/statin use.
- Baseline demographics and patient characteristics were analyzed using descriptive statistics.
Main Results:
- Younger patients (<65 years) had shorter diabetes duration and higher baseline HbA1c compared to older patients (≥65 years).
- Older patients had higher prevalence of hypertension, dyslipidemia, and prior CV events.
- Vildagliptin showed significant reductions in systolic blood pressure, LDL cholesterol, and weight in younger patients, but not older patients. Hypoglycemic event rates were lower with vildagliptin across both age groups compared to comparators.
Conclusions:
- The observed benefits of vildagliptin on systolic blood pressure, LDL cholesterol, weight, and hypoglycemia in younger T2DM patients may explain the reduced MACE risk in this demographic.
- These findings suggest age-related differences in treatment response and cardiovascular risk profiles influence vildagliptin's efficacy in T2DM.
Introduction:
In a meta-analysis, we observed a significant 37% relative risk reduction in prospectively adjudicated major adverse cardiac events [MACEs, comprising of non-fatal myocardial infarction, non-fatal stroke, cardiovascular (CV) death] with vildagliptin vs. comparators in younger (< 65 years) patients with type 2 diabetes mellitus (T2DM), while the risk was similar in older patients (≥ 65 years). We carried out an exploratory analysis to identify the patient characteristics and on-treatment effects that may have contributed to the different outcomes in the two age groups.
Methods:
On-treatment differences (vildagliptin vs. comparators) for the change from baseline in CV risk factors were analyzed using an analysis of covariance model with the baseline value for each variable of interest, treatment and study as covariates. Additional adjustments for background antihypertensive and statin use were performed when analyzing changes in blood pressure and lipids, respectively. Baseline characteristics and patient demographics were analyzed using descriptive statistics.
Results:
Patients aged < 65 years had shorter diabetes duration (4.4 vs. 8.2 years) and slightly higher glycated hemoglobin (HbA1c) at baseline (8.3% vs. 8.0%) than patients aged ≥ 65 years. More patients in the ≥ 65 year age group had hypertension (73.1% vs. 51.3%), dyslipidemia (53.3% vs. 43.9%) and a history of CV events (32.2% vs. 12.9%). There were small, but statistically significant differences in the change in HbA1c and total cholesterol in favor of vildagliptin relative to comparators, which were similar in both age groups. Significant differences were observed in the reduction in systolic blood pressure (SBP) (- 0.52 mmHg; 95% CI - 0.97, - 0.07; p = 0.023), low-density lipoprotein (LDL cholesterol) (- 0.12 mmol/l; 95% CI - 0.19, - 0.04; p = 0.002) and weight (- 0.48 kg; 95% CI - 0.95, - 0.01; p < 0.047) in patients < 65 years, but not in patients ≥ 65 years. The incidence of hypoglycemic events was lower in patients treated with vildagliptin [2.1 and 3.5 per 100 subject years exposure (SYEs) in < 65 and ≥ 65 years, respectively] than with comparators (5.8 and 7.5 per 100 SYEs, respectively).
Conclusion:
Based on our findings, it can be hypothesized that the positive effects of vildagliptin on SBP, LDL cholesterol, hypoglycemia and weight observed in younger, but not in older patients could be associated with the lower risk of MACE in younger patients with T2DM.
Funding:
Novartis.
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